Sample records for alert rhesus monkeys

  1. Bilirubin photoisomers in rhesus monkey serum.

    PubMed

    Okada, Hitoshi; Itoh, Susumu; Nii, Kohichiroh; Sugino, Masashiro; Fuke, Noriko; Koyano, Kosuke; Yasuda, Saneyuki; Kusaka, Takashi

    2018-05-23

    As rhesus monkeys exhibit physiological jaundice during the neonatal period, we used rhesus monkey serum to examine changes in bilirubin photoisomers. Bilirubin-rhesus monkey serum solution was irradiated with blue light-emitting diode, and changes in the absorbance and bilirubin fraction were compared with those in bilirubin- human serum albumin (HSA) and bilirubin-rat albumin solutions. The λ max decreased with light irradiation. The mean production rate of cyclobilirubin IXα was 1.98, 199 and 0.76 × 10 -2 /min in rhesus monkey serum, HSA and rat albumin, respectively. There was no significant difference between rhesus monkey serum and HSA. The (ZE)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.33, 0.45, and 0.10, respectively, differing significantly among the groups. The (EZ)-bilirubin IXα/(ZZ)-bilirubin IXα ratio was 0.020, 0.010, and 0.062, respectively, with no significant difference between rhesus monkey serum and HSA. The production rate of (EZ)-cyclobilirubin XIIIα(= (ZE)-cyclobilirubin XIIIα) was 0.73, 1.60, and 0.51 × 10 -2 /min, respectively, with differing significantly among the groups. The (EZ)-bilirubin IIIα/(ZZ)-bilirubin IIIα ratio was significantly different among the groups at 0.20, 0.38, and 0.15, respectively. This is the first report demonstrating the photoisomerization of bilirubin in rhesus monkey serum and the animal with the same cyclobilirubin production rate as HSA.Rhesus monkeys may be used as an animal model for neonatal hyperbilirubinemia in humans to evaluate the efficacy of phototherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  2. The susceptibility of rhesus monkeys to motion sickness

    NASA Technical Reports Server (NTRS)

    Corcoran, Meryl L.; Daunton, Nancy G.; Fox, Robert A.

    1990-01-01

    The susceptibility of rhesus monkeys to motion sickness was investigated using test conditions that are provocative for eliciting motion sickness in squirrel monkeys. Ten male rhesus monkeys and ten male Bolivian squirrel monkeys were rotated in the vertical axis at 150 deg/s for a maximum duration of 45 min. Each animal was tested in two conditions, continuous rotation and intermittent rotation. None of the rhesus monkeys vomited during the motion tests but all of the squirrel monkeys did. Differences were observed between the species in the amount of activity that occurred during motion test, with the squirrel monkeys being significantly more active than the rhesus monkeys. These results, while substantiating anecdotal reports of the resistance of rhesus monkeys to motion sickness, should be interpreted with caution because of the documented differences that exist between various species with regard to stimuli that are provocative for eliciting motion sickness.

  3. Functional specialization of medial auditory belt cortex in the alert rhesus monkey.

    PubMed

    Kusmierek, Pawel; Rauschecker, Josef P

    2009-09-01

    Responses of neural units in two areas of the medial auditory belt (middle medial area [MM] and rostral medial area [RM]) were tested with tones, noise bursts, monkey calls (MC), and environmental sounds (ES) in microelectrode recordings from two alert rhesus monkeys. For comparison, recordings were also performed from two core areas (primary auditory area [A1] and rostral area [R]) of the auditory cortex. All four fields showed cochleotopic organization, with best (center) frequency [BF(c)] gradients running in opposite directions in A1 and MM than in R and RM. The medial belt was characterized by a stronger preference for band-pass noise than for pure tones found medially to the core areas. Response latencies were shorter for the two more posterior (middle) areas MM and A1 than for the two rostral areas R and RM, reaching values as low as 6 ms for high BF(c) in MM and A1, and strongly depended on BF(c). The medial belt areas exhibited a higher selectivity to all stimuli, in particular to noise bursts, than the core areas. An increased selectivity to tones and noise bursts was also found in the anterior fields; the opposite was true for highly temporally modulated ES. Analysis of the structure of neural responses revealed that neurons were driven by low-level acoustic features in all fields. Thus medial belt areas RM and MM have to be considered early stages of auditory cortical processing. The anteroposterior difference in temporal processing indices suggests that R and RM may belong to a different hierarchical level or a different computational network than A1 and MM.

  4. Chimpanzee counting and rhesus monkey ordinality judgments

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.; Washburn, David A.; Hopkins, William D.; Savage-Rumbaugh, E. S.

    1991-01-01

    An investigation is conducted to address the questions of whether chimpanzees can count and whether rhesus monkeys can differentiate written numbers. One investigation demonstrates the capacity of a chimpanzee to produce a quantity of responses appropriate to a given Arabic numeral. Rhesus monkeys are shown to have the capability for making fine differentiations between quantities of pellets and Arabic numerals.

  5. Eradication of Herpesvirus simiae from a Rhesus Monkey Breeding Colony. B-virus Eradication in Breeding Rhesus

    DTIC Science & Technology

    1992-10-01

    Herpesvirus simiae from a Rhesus Monkey Breeding Colony B-virus Eradication in Breeding Rhesus 6. AUTHOR(S) Jerome J. Sauber , John W. Fanton, Roger C...for Laboratory Animal Science October 1992 An Attempt to Eradicate Herpesvirus simiae from a Rhesus Monkey Breeding Colony Jerome J. Sauber , John W

  6. Reference values of clinical chemistry and hematology parameters in rhesus monkeys (Macaca mulatta).

    PubMed

    Chen, Younan; Qin, Shengfang; Ding, Yang; Wei, Lingling; Zhang, Jie; Li, Hongxia; Bu, Hong; Lu, Yanrong; Cheng, Jingqiu

    2009-01-01

    Rhesus monkey models are valuable to the studies of human biology. Reference values for clinical chemistry and hematology parameters of rhesus monkeys are required for proper data interpretation. Whole blood was collected from 36 healthy Chinese rhesus monkeys (Macaca mulatta) of either sex, 3 to 5 yr old. Routine chemistry and hematology parameters, and some special coagulation parameters including thromboelastograph and activities of coagulation factors were tested. We presented here the baseline values of clinical chemistry and hematology parameters in normal Chinese rhesus monkeys. These data may provide valuable information for veterinarians and investigators using rhesus monkeys in experimental studies.

  7. Rhesus monkey heart rate during exercise

    NASA Technical Reports Server (NTRS)

    Delorge, J.; Thach, J. S., Jr.

    1972-01-01

    Various schedules of reinforcement and their relation to heart rates of rhesus monkeys during exercise are described. All the reinforcement schedules produced 100 per cent or higher increments in the heart rates of the monkeys during exercise. Resting heart rates were generally much lower than those previously reported, which was attributed to the lack of physical restraint of the monkeys during recording.

  8. Physiology responses of Rhesus monkeys to vibration

    NASA Astrophysics Data System (ADS)

    Hajebrahimi, Zahra; Ebrahimi, Mohammad; Alidoust, Leila; Arabian Hosseinabadi, Maedeh

    Vibration is one of the important environmental factors in space vehicles that it can induce severe physiological responses in most of the body systems such as cardiovascular, respiratory, skeletal, endocrine, and etc. This investigation was to assess the effect of different vibration frequencies on heart rate variability (HRV), electrocardiograms (ECG) and respiratory rate in Rhesus monkeys. Methods: two groups of rhesus monkey (n=16 in each group) was selected as control and intervention groups. Monkeys were held in a sitting position within a specific fixture. The animals of this experiment were vibrated on a table which oscillated right and left with sinusoidal motion. Frequency and acceleration for intervention group were between the range of 1 to 2000 Hz and +0.5 to +3 G during 36 weeks (one per week for 15 min), respectively. All of the animals passed the clinical evaluation (echocardiography, sonography, radiography and blood analysis test) before vibration test and were considered healthy and these tests repeated during and at the end of experiments. Results and discussions: Our results showed that heart and respiratory rates increased significantly in response to increased frequency from 1 to 60 Hz (p <0.05) directly with the +G level reaching a maximum (3G) within a seconds compare to controls. There were no significant differences in heart and respiratory rate from 60 t0 2000 Hz among studied groups. All monkeys passed vibration experiment successfully without any arrhythmic symptoms due to electrocardiography analysis. Conclusion: Our results indicate that vibration in low frequency can effect respiratory and cardiovascular function in rhesus monkey. Keywords: Vibration, rhesus monkey, heart rate, respiratory rate

  9. Rhesus monkeys lack a consistent peak-end effect.

    PubMed

    Xu, Eric R; Knight, Emily J; Kralik, Jerald D

    2011-12-01

    In humans, the order of receiving sequential rewards can significantly influence the overall subjective utility of an outcome. For example, people subjectively rate receiving a large reward by itself significantly higher than receiving the same large reward followed by a smaller one (Do, Rupert, & Wolford, 2008). This result is called the peak-end effect. A comparative analysis of order effects can help determine the generality of such effects across primates, and we therefore examined the influence of reward-quality order on decision making in three rhesus macaque monkeys (Macaca mulatta). When given the choice between a high-low reward sequence and a low-high sequence, all three monkeys preferred receiving the high-value reward first. Follow-up experiments showed that for two of the three monkeys their choices depended specifically on reward-quality order and could not be accounted for by delay discounting. These results provide evidence for the influence of outcome order on decision making in rhesus monkeys. Unlike humans, who usually discount choices when a low-value reward comes last, rhesus monkeys show no such peak-end effect.

  10. Pancreas anatomy and surgical procedure for pancreatectomy in rhesus monkeys.

    PubMed

    Zhang, Yi; Fu, Lan; Lu, Yan-Rong; Guo, Zhi-Guang; Zhang, Zhao-Da; Cheng, Jing-Qiu; Hu, Wei-Ming; Liu, Xu-Bao; Mai, Gang; Zeng, Yong; Tian, Bo-Le

    2011-12-01

    The aim of this study was to investigate the pancreas anatomy and surgical procedure for harvesting pancreas for islet isolation while performing pancreatectomy to induce diabetes in rhesus monkeys. The necropsy was performed in three cadaveric monkeys. Two monkeys underwent the total pancreatectomy and four underwent partial pancreatectomy (70-75%). The greater omentum without ligament to transverse colon, the cystic artery arising from the proper hepatic artery and the branches supplying the paries posterior gastricus from the splenic artery were observed. For pancreatectomy, resected pancreas can be used for islet isolation. Diabetes was not induced in the monkeys undergoing partial pancreatectomy (70-75%). Pancreas anatomy in rhesus monkeys is not the same as in human. Diabetes can be induced in rhesus monkeys by total but not partial pancreatectomy (70-75%). Resected pancreas can be used for islet isolation while performing pancreatectomy to induce diabetes. © 2011 John Wiley & Sons A/S.

  11. Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

    PubMed Central

    Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; Borducchi, Erica N.; Iampietro, M. Justin; Bricault, Christine A.; Teigler, Jeffrey E.; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A.; Zhao, Guoyan; Virgin, Herbert W.; Korber, Bette

    2014-01-01

    ABSTRACT Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. IMPORTANCE Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. PMID:25410856

  12. Construction and evaluation of novel rhesus monkey adenovirus vaccine vectors.

    PubMed

    Abbink, Peter; Maxfield, Lori F; Ng'ang'a, David; Borducchi, Erica N; Iampietro, M Justin; Bricault, Christine A; Teigler, Jeffrey E; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A; Zhao, Guoyan; Virgin, Herbert W; Korber, Bette; Barouch, Dan H

    2015-02-01

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. Although there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  13. Improved Methods for Electroacupuncture and Electromyographic Recordings in Normal and Parkinsonian Rhesus Monkeys

    PubMed Central

    Zhao, Feng; Fan, Xiaotong; Grondin, Richard; Edwards, Ramsey; Forman, Eric; Moorehead, Jennifer; Gerhardt, Greg; Wang, Xiaomin; Zhang, Zhiming

    2010-01-01

    Although acupuncture has been widely and routinely used in healthcare in the USA, its use has been based more on empirical observation than on scientific knowledge. Therefore, there is a great need for better understanding the underlying mechanism(s) of action. A great body of evidence supports that nonhuman primates are a candidate for studying human diseases. However, the use of nonhuman primates in neurophysiological, neuroimaging and neurochemical studies is extremely challenging, especially under fully conscious, alert conditions. In the present study, we developed a protocol for safely performing acupuncture, electro-acupuncture (EA) and electromyography (EMG) in both normal nonhuman primates and animals with parkinsonian-like symptoms. Four normal and four hemiparkinsonian middle-aged rhesus monkeys were extensively trained, behaviorally monitored, and received both EA and EMG for several months. The results demonstrated that (1) all rhesus monkeys used in the study could be trained for procedures including EA and EMG; (2) all animals tolerated the procedures involving needle/electrode insertion; (3) EA procedures used in the study did not adversely alter the animal’s locomotor activities; rather, MPTP-treated animals showed a significant improvement in movement speed; and (4) EMG detected significant differences in muscle activity between the arms with and without MPTP-induced rigidity. Our results support that rhesus monkeys can be used as an experimental animal model to study EA and that EMG has the potential to be used to objectively assess the effects of antiparkinsonian therapies. The results also indicate that animals, especially those with parkinsonian-like symptoms, could benefit from long-term EA stimulations. PMID:20654649

  14. Induction, management, and complications of streptozotocin-induced diabetes mellitus in rhesus monkeys.

    PubMed

    Kim, Jong-Min; Shin, Jun-Seop; Min, Byoung-Hoon; Kim, Hyun-Je; Kim, Jung-Sik; Yoon, Il-Hee; Jeong, Won-Young; Lee, Ga-Eul; Kim, Min-Sun; Kim, Ju-Eun; Jin, Sang-Man; Park, Chung-Gyu

    2016-11-01

    Diabetes mellitus (DM) model using streptozotocin (STZ) which induces chemical ablation of β cell in the pancreas has been widely used for various research purposes in non-human primates. However, STZ has been known to have a variety of adverse effects such as nephrotoxicity, hepatotoxicity, and even mortality. The purpose of this study is to report DM induction by STZ, toxicity associated with STZ and procedure and complication of exogenous insulin treatment for DM management in rhesus monkeys (Macaca mulatta) that are expected to be transplanted with porcine islets within 2 months. Streptozotocin (immediately dissolved in normal saline, 110 mg/kg) was slowly infused via central catheter for 10 minutes in 22 rhesus monkeys. Clinical signs, complete blood count and blood chemistry were monitored to evaluate toxicity for 1 week after STZ injection. Monkey basal C-peptides were measured and intravenous glucose tolerance test was performed to confirm complete induction of DM. Exogenous insulin was subcutaneously injected to maintain blood glucose in diabetic rhesus monkeys and the complications were recorded while in insulin treatment. Severe salivation and vomiting were observed within 1 hour after STZ injection in 22 rhesus monkeys. One monkey died at 6 hours after STZ injection and the reason for the death was unknown. Pancreatitis was noticed in one monkey after STZ injection, but the monkey recovered after 5 days by medical treatment. Serum total protein and albumin decreased whereas the parameters for the liver function such as aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase significantly increased (P<.05) after STZ injection, but they were resolved within 1 week. Azotemia was not observed. Monkey fasting C-peptide levels after STZ injection were <0.1 ng/mL in 18 rhesus monkeys, but 0.34, 0.22, 0.16 ng/mL in three monkeys, respectively. The value of daily insulin requirement was 0.92±0.26IU/kg/d (range=0.45-1.29) in

  15. The Effect of Heterogeneity on Numerical Ordering in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Cantlon, Jessica F.; Brannon, Elizabeth M.

    2006-01-01

    We investigated how within-stimulus heterogeneity affects the ability of rhesus monkeys to order pairs of the numerosities 1 through 9. Two rhesus monkeys were tested in a touch screen task where the variability of elements within each visual array was systematically varied by allowing elements to vary in color, size, shape, or any combination of…

  16. Spaceflight and immune responses of Rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1994-01-01

    Evidence from both human and rodent studies indicates that alterations in immunological parameters occur after space flight. The objective of this project is to determine the effects of space flight on immune responses of Rhesus monkeys. The expected significance of the work is a determination of the range of immunological functions of the Rhesus monkey, a primate similar in many ways to man, affected by space flight. Changes in immune responses that could yield alterations in resistance to infection may be determined as well as the duration of alterations in immune responses. Additional information on the nature of cellular interactions for the generation of immune responses may also be obtained.

  17. Ethograms indicate stable well-being during prolonged training phases in rhesus monkeys used in neurophysiological research.

    PubMed

    Hage, Steffen R; Ott, Torben; Eiselt, Anne-Kathrin; Jacob, Simon N; Nieder, Andreas

    2014-01-01

    Awake, behaving rhesus monkeys are widely used in neurophysiological research. Neural signals are typically measured from monkeys trained with operant conditioning techniques to perform a variety of behavioral tasks in exchange for rewards. Over the past years, monkeys' psychological well-being during experimentation has become an increasingly important concern. We suggest objective criteria to explore whether training sessions during which the monkeys work under controlled water intake over many days might affect their behavior. With that aim, we analyzed a broad range of species-specific behaviors over several months ('ethogram') and used these ethograms as a proxy for the monkeys' well-being. Our results show that monkeys' behavior during training sessions is unaffected by the duration of training-free days in-between. Independently of the number of training-free days (two or nine days) with ad libitum food and water supply, the monkeys were equally active and alert in their home group cages during training phases. This indicates that the monkeys were well habituated to prolonged working schedules and that their well-being was stably ensured during the training sessions.

  18. Tonal frequency affects amplitude but not topography of rhesus monkey cranial EEG components.

    PubMed

    Teichert, Tobias

    2016-06-01

    The rhesus monkey is an important model of human auditory function in general and auditory deficits in neuro-psychiatric diseases such as schizophrenia in particular. Several rhesus monkey studies have described homologs of clinically relevant auditory evoked potentials such as pitch-based mismatch negativity, a fronto-central negativity that can be observed when a series of regularly repeating sounds is disrupted by a sound of different tonal frequency. As a result it is well known how differences of tonal frequency are represented in rhesus monkey EEG. However, to date there is no study that systematically quantified how absolute tonal frequency itself is represented. In particular, it is not known if frequency affects rhesus monkey EEG component amplitude and topography in the same way as previously shown for humans. A better understanding of the effect of frequency may strengthen inter-species homology and will provide a more solid foundation on which to build the interpretation of frequency MMN in the rhesus monkey. Using arrays of up to 32 cranial EEG electrodes in 4 rhesus macaques we identified 8 distinct auditory evoked components including the N85, a fronto-central negativity that is the presumed homolog of the human N1. In line with human data, the amplitudes of most components including the N85 peaked around 1000 Hz and were strongly attenuated above ∼1750 Hz. Component topography, however, remained largely unaffected by frequency. This latter finding may be consistent with the known absence of certain anatomical structures in the rhesus monkey that are believed to cause the changes in topography in the human by inducing a rotation of generator orientation as a function of tonal frequency. Overall, the findings are consistent with the assumption of a homolog representation of tonal frequency in human and rhesus monkey EEG. Copyright © 2016 Elsevier B.V. All rights reserved.

  19. Transmission and Absorption Coefficients for Ocular Media of the Rhesus Monkey

    DTIC Science & Technology

    1978-12-01

    Report SAM-TR.78-32 @LEVtt ^ \\ TRANSMISSION AND ABSORPTION COEFFICIENTS FOR OGVLAR MEDIA OF THE RHESUS MONKEY 30 JO \\ Edward F. Maher... MONKEY 5. I il | ||| MhlHWr W PI liriTl i I III I 5" . Final Report ""■"’ 15 Sep 74 - 15 Sep 76 6 «HFORMtMO OHG REPORT KUMBE...for these calculations were performed spectrophotometrically using freshly enucleated rhesus monkey eyes and narrow-bandwidth radiation. Much of the

  20. Nuclear-mitochondrial incompatibility in interorder rhesus monkey-cow embryos derived from somatic cell nuclear transfer.

    PubMed

    Kwon, Daekee; Koo, Ok-Jae; Kim, Min-Jung; Jang, Goo; Lee, Byeong Chun

    2016-10-01

    Monkey interorder somatic cell nuclear transfer (iSCNT) using enucleated cow oocytes yielded poor blastocysts development and contradictory results among research groups. Determining the reason for this low blastocyst development is a prerequisite for optimizing iSCNT in rhesus monkeys. The aim of this study was to elucidate nuclear-mitochondrial incompatibility of rhesus monkey-cow iSCNT embryos and its relationship to low blastocyst development. Cytochrome b is a protein of complex III of the electron transport chain (ETC). According to meta-analysis of amino acid sequences, the homology of cytochrome b is 75 % between rhesus monkeys and cattle. To maintain the function of ETC after iSCNT, 4n iSCNT embryos were produced by fusion of non-enucleated cow oocytes and rhesus monkey somatic cells. The blastocyst development rate of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Formation of reactive oxygen species (ROS) is an indirect indicator of ETC activity of cells. The ROS levels of 4n iSCNT embryos was higher than that of 2n embryos (P < 0.01). Collectively, rhesus monkey iSCNT embryos reconstructed with cow oocytes have nuclear-mitochondrial incompatibility due to fundamental species differences between rhesus monkeys and cattle. Nuclear-mitochondrial incompatibility seems to correlate with low ETC activity and extremely low blastocyst development of rhesus monkey-cow iSCNT embryos.

  1. Lifespan Trajectories of White Matter Changes in Rhesus Monkeys.

    PubMed

    Kubicki, M; Baxi, M; Pasternak, O; Tang, Y; Karmacharya, S; Chunga, N; Lyall, A E; Rathi, Y; Eckbo, R; Bouix, S; Mortazavi, F; Papadimitriou, G; Shenton, M E; Westin, C F; Killiany, R; Makris, N; Rosene, D L

    2018-04-26

    Progress in neurodevelopmental brain research has been achieved through the use of animal models. Such models not only help understanding biological changes that govern brain development, maturation and aging, but are also essential for identifying possible mechanisms of neurodevelopmental and age-related chronic disorders, and to evaluate possible interventions with potential relevance to human disease. Genetic relationship of rhesus monkeys to humans makes those animals a great candidate for such models. With the typical lifespan of 25 years, they undergo cognitive maturation and aging that is similar to this observed in humans. Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking white matter brain maturation and aging. While lifespan trajectories of white matter changes have been mapped in humans, such knowledge is not available for nonhuman primates. Here, we analyze and model lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys. We report quantitative parameters (including slopes and peaks) of lifespan trajectories for 8 individual white matter tracts. We show different trajectories for cellular and extracellular microstructural imaging components that are associated with white matter maturation and aging, and discuss similarities and differences between those in humans and rhesus monkeys, the importance of our findings, and future directions for the field.Significance Statement: Quantitative structural neuroimaging has been proposed as one of the candidate in vivo biomarkers for tracking brain maturation and aging. While lifespan trajectories of structural white matter changes have been mapped in humans, such knowledge is not available for rhesus monkeys. We present here results of the analysis and modeling of the lifespan trajectories of white matter microstructure using in vivo diffusion imaging in a sample of 44 rhesus monkeys (age 4

  2. Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

    DOE PAGES

    Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; ...

    2014-11-19

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

  3. Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

  4. Spontaneous Metacognition in Rhesus Monkeys.

    PubMed

    Rosati, Alexandra G; Santos, Laurie R

    2016-09-01

    Metacognition is the ability to think about thinking. Although monitoring and controlling one's knowledge is a key feature of human cognition, its evolutionary origins are debated. In the current study, we examined whether rhesus monkeys (Macaca mulatta; N = 120) could make metacognitive inferences in a one-shot decision. Each monkey experienced one of four conditions, observing a human appearing to hide a food reward in an apparatus consisting of either one or two tubes. The monkeys tended to search the correct location when they observed this baiting event, but engaged in information seeking-by peering into a center location where they could check both potential hiding spots-if their view had been occluded and information seeking was possible. The monkeys only occasionally approached the center when information seeking was not possible. These results show that monkeys spontaneously use information about their own knowledge states to solve naturalistic foraging problems, and thus provide the first evidence that nonhumans exhibit information-seeking responses in situations with which they have no prior experience. © The Author(s) 2016.

  5. Spaceflight and Immune Responses of Rhesus Monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald

    1997-01-01

    In the grant period, we perfected techniques for determination of interleukin production and leukocyte subset analysis of rhesus monkeys. These results are outlined in detail in publication number 2, appended to this report. Additionally, we participated in the ARRT restraint test to determine if restraint conditions for flight in the Space Shuttle could contribute to any effects of space flight on immune responses. All immunological parameters listed in the methods section were tested. Evaluation of the data suggests that the restraint conditions had minimal effects on the results observed, but handling of the monkeys could have had some effect. These results are outlined in detail in manuscript number 3, appended to this report. Additionally, to help us develop our rhesus monkey immunology studies, we carried out preliminary studies in mice to determine the effects of stressors on immunological parameters. We were able to show that there were gender-based differences in the response of immunological parameters to a stressor. These results are outlined in detail in manuscript number 4, appended to this report.

  6. Circulation of Campylobacter spp. in rhesus monkeys (Macaca mulatta) held in captivity: a longitudinal study.

    PubMed

    Andrade, Márcia Cristina Ribeiro; Gabeira, Sanny Cerqueira de Oliveira; Abreu-Lopes, Danielle; Esteves, Wagner Thadeu Cardoso; Vilardo, Mônica de Castro Britto; Thomé, Jacqueline D'arc da Silva; Cabello, Pedro Hernan; Lauria-Filgueiras, Ana Luzia

    2007-02-01

    Campylobacteriosis is an extremely important zoonosis, circulating freely in the environment. In nonhuman primates kept in open facilities and bred for experimental purposes, the presence of Campylobacter spp. could cause severe damage to the production and interfere with the results of scientific research. In this paper, we assessed the circulation of Campylobacter spp. in a colony of clinically healthy rhesus monkeys (Macaca mulatta) destined to research. The analysis was carried out during seven non-consecutive years. Data showed that despite several changes made in animal management along the studied years in order to control this zoonosis, reduction of bacterial charge did not occur. Significant differences among the age groups and sex were observed. Infants showed higher susceptibility than adult animals. In general males were more infected than females. Modifications adopted in the handling techniques need to be reviewed with the intent of improving the production, reducing bacterial infection of the stock and avoiding undesirable cross reactions in the research carried out with these animals. Therefore, this paper alerts professionals that work directly with captive rhesus monkeys about the risks of Campylobacter spp. infection and possible interference on the experimental procedures.

  7. Lactobacillus and Pediococcus species richness and relative abundance in the vagina of rhesus monkeys (Macaca mulatta)

    PubMed Central

    Gravett, Michael G.; Jin, Ling; Pavlova, Sylvia I.; Tao, Lin

    2012-01-01

    Background The rhesus monkey is an important animal model to study human vaginal health to which lactic acid bacteria play a significant role. However, the vaginal lactic acid bacterial species richness and relative abundance in rhesus monkeys is largely unknown. Methods Vaginal swab samples were aseptically obtained from 200 reproductive aged female rhesus monkeys. Following Rogosa agar plating, single bacterial colonies representing different morphotypes were isolated and analyzed for whole-cell protein profile, species-specifc PCR, and 16S rRNA gene sequence. Results A total of 510 Lactobacillus strains of 17 species and one Pediococcus acidilactici were identified. The most abundant species was L. reuteri, which colonized the vaginas of 86% monkeys. L. johnsonii was the second most abundant species, which colonized 36% of monkeys. The majority of monkeys were colonized by multiple Lactobacillus species. Conclusions The vaginas of rhesus monkeys are frequently colonized by multiple Lactobacillus species, dominated by L. reuteri. PMID:22429090

  8. The rhesus monkey as a model for testing the immunological effects of space flight

    NASA Astrophysics Data System (ADS)

    Sonnenfeld, G.; Schaffar, L.; Schmitt, D. A.; Peres, C.; Miller, E. S.

    1994-08-01

    The Rhesus monkey has been proposed as a model for the effects of space flight on immunity. In order to determine the feasibility of the use of the Rhesus monkey as a model, we studied the use of Rhesus monkey cells for immunological procedures that have been shown to be affected by space flight in both rodents and humans. We have shown that both lymph node cells and peripheral blood leukocytes can be stained with monoclonal antibodies to detect the following surface markers: CD4, CD-8, Ia and surface immunoglobulin. Also, the level of Ia antigen expression was increased by treatment of the cells with human interferon-gamma. In addition, cells were induced to produce interferons and interleukins. Isolated neutrophils also demonstrated increased oxidative burst. These data indicate that the Rhesus monkey will be a useful model for space flight studies of immunity.

  9. The Rhesus monkey as a model for testing the immunological effects of space flight

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.; Schaffar, L.; Schmitt, D. A.; Peres, C.; Miller, E. S.

    1994-01-01

    The Rhesus monkey has been proposed as a model for the effects of space flight on immunity. In order to determine the feasibility of the use of the Rhesus monkey as a model, we studied the use of Rhesus monkey cells for immunological procedures that have been shown to be affected by space flight in both rodents and humans. We have shown that both lymph node cells and peripheral blood leukocytes can be stained with monoclonal antibodies to detect the following surface markers: CD4, CD-8, Ia and surface immunoglobulin. Also, the level of Ia antigen expression was increased by treatment of the cells with human interferon-gamma. In addition, cells were induced to produce interferons and interleukins. Isolated neutrophils also demonstrated increased oxidative burst. These data indicate that the Rhesus monkey will be a useful model for space flight studies of immunity.

  10. Homogeneous antibodies in lethally irradiated and autologous bone marrow reconstituted Rhesus monkeys

    PubMed Central

    Van Den Berg, Pleuntje; Radl, J.; Löwenberg, B.; Swart, A. C. W.

    1976-01-01

    Ten Rhesus monkeys were lethally irradiated and reconstituted with autologous bone marrow. During the restoration period, the animals were immunized with DNP–Rhesus albumin and IgA1λ-10S human paraprotein. One or more transient homogeneous immunoglobulin components appeared in sera of all experimental monkeys. In four animals, these homogeneous immunoglobulins were shown to be specific antibodies against DNP–Rhesus albumin. They gradually became as heterogeneous as those in control monkeys which were immunized but not irradiated and transplanted. The onset of the specific antibody response after immunization was slightly delayed in the experimental group. On determining the time necessary to reach normalization of the overall immunoglobulin levels and the normal heterogeneity of the immunoglobulin spectrum, it was found to be more than 1 year in most of the animals. ImagesFig. 1

  11. Video-task acquisition in rhesus monkeys (Macaca mulatta) and chimpanzees (Pan troglodytes): a comparative analysis

    NASA Technical Reports Server (NTRS)

    Hopkins, W. D.; Washburn, D. A.; Hyatt, C. W.; Rumbaugh, D. M. (Principal Investigator)

    1996-01-01

    This study describes video-task acquisition in two nonhuman primate species. The subjects were seven rhesus monkeys (Macaca mulatta) and seven chimpanzees (Pan troglodytes). All subjects were trained to manipulate a joystick which controlled a cursor displayed on a computer monitor. Two criterion levels were used: one based on conceptual knowledge of the task and one based on motor performance. Chimpanzees and rhesus monkeys attained criterion in a comparable number of trials using a conceptually based criterion. However, using a criterion based on motor performance, chimpanzees reached criterion significantly faster than rhesus monkeys. Analysis of error patterns and latency indicated that the rhesus monkeys had a larger asymmetry in response bias and were significantly slower in responding than the chimpanzees. The results are discussed in terms of the relation between object manipulation skills and video-task acquisition.

  12. Rhesus monkeys (Macaca mulatta) map number onto space

    PubMed Central

    Drucker, Caroline B.; Brannon, Elizabeth M.

    2014-01-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance, location, and spacing of the vertical array. We next asked whether monkeys show a spatially-oriented number mapping by testing their responses to the same five-element stimulus array rotated ninety degrees into a horizontal line. In these horizontal probe trials, monkeys preferentially selected the fourth position from the left, but not the fourth position from the right. Our results indicate that rhesus macaques map number onto space, suggesting that the association between number and space in human cognition is not purely a result of cultural experience and instead has deep evolutionary roots. PMID:24762923

  13. Rhesus monkeys (Macaca mulatta) map number onto space.

    PubMed

    Drucker, Caroline B; Brannon, Elizabeth M

    2014-07-01

    Humans map number onto space. However, the origins of this association, and particularly the degree to which it depends upon cultural experience, are not fully understood. Here we provide the first demonstration of a number-space mapping in a non-human primate. We trained four adult male rhesus macaques (Macaca mulatta) to select the fourth position from the bottom of a five-element vertical array. Monkeys maintained a preference to choose the fourth position through changes in the appearance, location, and spacing of the vertical array. We next asked whether monkeys show a spatially-oriented number mapping by testing their responses to the same five-element stimulus array rotated ninety degrees into a horizontal line. In these horizontal probe trials, monkeys preferentially selected the fourth position from the left, but not the fourth position from the right. Our results indicate that rhesus macaques map number onto space, suggesting that the association between number and space in human cognition is not purely a result of cultural experience and instead has deep evolutionary roots. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Cytokine responses in young and old rhesus monkeys: effect of caloric restriction.

    PubMed

    Mascarucci, Paolo; Taub, Dennis; Saccani, Simona; Paloma, Marjorie A; Dawson, Harry; Roth, George S; Lane, Mark A; Ingram, Donald K

    2002-05-01

    Caloric restriction (CR) is the only known intervention demonstrated to retard a great variety of aging processes, extend median and maximum life-span, and decrease the incidence of age-associated diseases in mammals. Paralleling findings from rodent studies, studies in rhesus monkeys (Macaca mulatta) suggest that CR may retard many age-sensitive parameters in primates. A recent study in rhesus monkeys showed age-related dysregulation of cytokine levels. Specifically, age-related increases in interleukin-10 (IL-10) and IL-6 proteins were observed in supernatants from lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs), and interferon-gamma (IFN-gamma) protein exhibited an age-related decrease in phytohemagglutinin (PHA)-stimulated PBMCs. To investigate effects of CR on age-related changes in cytokine production, we obtained PBMCs from control and CR rhesus monkeys aged 6-7 and 22-25 years. We evaluated IL-10 and IL-6 protein and gene expression after exposure to LPS and IFN-gamma protein and gene expression after PHA stimulation. The results revealed significantly higher levels of IFN-gamma protein and gene expression in aged monkeys on CR for 2 years compared with controls. No significant CR effects were observed on IL-10 and IL-6 protein levels. IFN-gamma plays an important role in the initial defense mechanism against viral and microbial disease and cancer. Altered regulation of IFN-gamma in old CR rhesus monkeys may be a key factor in reducing cancer incidence and other age-associated diseases.

  15. Auditory Function in Rhesus Monkeys: Effects of Aging and Caloric Restriction in the Wisconsin Monkeys Five Years Later

    PubMed Central

    Fowler, Cynthia G.; Chiasson, Kirstin Beach; Leslie, Tami Hanson; Thomas, Denise; Beasley, T. Mark; Kemnitz, Joseph W.; Weindruch, Richard

    2010-01-01

    Caloric restriction (CR) slows aging in many species and protects some animals from age-related hearing loss (ARHL), but the effect on humans is not yet known. Because rhesus monkeys are long-lived primates that are phylogenically closer to humans than other research animals are, they provide a better model for studying the effects of CR in aging and ARHL. Subjects were from the pool of 55 rhesus monkeys aged 15–28 years who had been in the Wisconsin study on CR and aging for 8–13.5 years. Distortion product otoacoustic emissions (DPOAE) with f2 frequencies from 2211–8837 Hz and auditory brainstem response (ABR) thresholds from clicks and 8, 16, and 32 kHz tone bursts were obtained. DPOAE levels declined linearly at approximately 1 dB/year, but that rate doubled for the highest frequencies in the oldest monkeys. There were no interactions for diet condition or sex. ABR thresholds to clicks and tone bursts showed increases with aging. Borderline significance was shown for diet in the thresholds at 8 kHz stimuli, with monkeys on caloric restriction having lower thresholds. Because the rhesus monkeys have a maximum longevity of 40 years, the full benefits of CR may not yet be realized. PMID:20079820

  16. Risky business: rhesus monkeys exhibit persistent preferences for risky options.

    PubMed

    Xu, Eric R; Kralik, Jerald D

    2014-01-01

    Rhesus monkeys have been shown to prefer risky over safe options in experiential decision-making tasks. These findings might be due, however, to specific contextual factors, such as small amounts of fluid reward and minimal costs for risk-taking. To better understand the factors affecting decision-making under risk in rhesus monkeys, we tested multiple factors designed to increase the stakes including larger reward amounts, distinct food items rather than fluid reward, a smaller number of trials per session, and risky options with greater variation that also included non-rewarded outcomes. We found a consistent preference for risky options, except when the expected value of the safe option was greater than the risky option. Thus, with equivalent mean utilities between the safe and risky options, rhesus monkeys appear to have a robust preference for the risky options in a broad range of circumstances, akin to the preferences found in human children and some adults in similar tasks. One account for this result is that monkeys make their choices based on the salience of the largest payoff, without integrating likelihood and value across trials. A related idea is that they fail to override an impulsive tendency to select the option with the potential to obtain the highest possible outcome. Our results rule out strict versions of both accounts and contribute to an understanding of the diversity of risky decision-making among primates.

  17. Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys.

    PubMed

    Barouch, Dan H; Liu, Jinyan; Li, Hualin; Maxfield, Lori F; Abbink, Peter; Lynch, Diana M; Iampietro, M Justin; SanMiguel, Adam; Seaman, Michael S; Ferrari, Guido; Forthal, Donald N; Ourmanov, Ilnour; Hirsch, Vanessa M; Carville, Angela; Mansfield, Keith G; Stablein, Donald; Pau, Maria G; Schuitemaker, Hanneke; Sadoff, Jerald C; Billings, Erik A; Rao, Mangala; Robb, Merlin L; Kim, Jerome H; Marovich, Mary A; Goudsmit, Jaap; Michael, Nelson L

    2012-01-04

    Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.

  18. Canine distemper outbreak in rhesus monkeys, China.

    PubMed

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang; Hu, Rongliang

    2011-08-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People's Republic of China. Approximately 10,000 animals were infected (25%-60% disease incidence); 5%-30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain.

  19. Comprehensive analysis of the T-cell receptor beta chain gene in rhesus monkey by high throughput sequencing

    PubMed Central

    Li, Zhoufang; Liu, Guangjie; Tong, Yin; Zhang, Meng; Xu, Ying; Qin, Li; Wang, Zhanhui; Chen, Xiaoping; He, Jiankui

    2015-01-01

    Profiling immune repertoires by high throughput sequencing enhances our understanding of immune system complexity and immune-related diseases in humans. Previously, cloning and Sanger sequencing identified limited numbers of T cell receptor (TCR) nucleotide sequences in rhesus monkeys, thus their full immune repertoire is unknown. We applied multiplex PCR and Illumina high throughput sequencing to study the TCRβ of rhesus monkeys. We identified 1.26 million TCRβ sequences corresponding to 643,570 unique TCRβ sequences and 270,557 unique complementarity-determining region 3 (CDR3) gene sequences. Precise measurements of CDR3 length distribution, CDR3 amino acid distribution, length distribution of N nucleotide of junctional region, and TCRV and TCRJ gene usage preferences were performed. A comprehensive profile of rhesus monkey immune repertoire might aid human infectious disease studies using rhesus monkeys. PMID:25961410

  20. Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Asgharian, Bahman; Price, Owen; McClellan, Gene

    2012-11-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of themore » animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 µm in size were examined for endotracheal and and up to 5 µm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Finally, future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.« less

  1. Development of a rhesus monkey lung geometry model and application to particle deposition in comparison to humans

    PubMed Central

    Asgharian, Bahman; Price, Owen; McClellan, Gene; Corley, Rick; Einstein, Daniel R.; Jacob, Richard E.; Harkema, Jack; Carey, Stephan A.; Schelegle, Edward; Hyde, Dallas; Kimbell, Julia S.; Miller, Frederick J.

    2016-01-01

    The exposure-dose-response characterization of an inhalation hazard established in an animal species needs to be translated to an equivalent characterization in humans relative to comparable doses or exposure scenarios. Here, the first geometry model of the conducting airways for rhesus monkeys is developed based upon CT images of the conducting airways of a 6-month-old male, rhesus monkey. An algorithm was developed for adding the alveolar region airways using published rhesus morphometric data. The resultant lung geometry model can be used in mechanistic particle or gaseous dosimetry models. Such dosimetry models require estimates of the upper respiratory tract volume of the animal and the functional residual capacity, as well as of the tidal volume and breathing frequency of the animal. The relationship of these variables to rhesus monkeys of differing body weights was established by synthesizing and modeling published data as well as modeling pulmonary function measurements on 121 rhesus control animals. Deposition patterns of particles up to 10 μm in size were examined for endotracheal and and up to 5 μm for spontaneous breathing in infant and young adult monkeys and compared to those for humans. Deposition fraction of respirable size particles was found to be higher in the conducting airways of infant and young adult rhesus monkeys compared to humans. Due to the filtering effect of the conducting airways, pulmonary deposition in rhesus monkeys was lower than that in humans. Future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model. PMID:23121298

  2. Single subcutaneous dosing of cefovecin in rhesus monkeys (Macaca mulatta): a pharmacokinetic study.

    PubMed

    Bakker, J; Thuesen, L R; Braskamp, G; Skaanild, M T; Ouwerling, B; Langermans, J A M; Bertelsen, M F

    2011-10-01

    Cefovecin is a third-generation cephalosporin approved for antibacterial treatment with a 14-day dosing interval in dogs and cats. This antibiotic may also be useful for zoo and wildlife veterinary medicine, because of its broad spectrum and long duration of activity. The aim of the study was to determine whether cefovecin is a suitable antibiotic to prevent skin wound infection in rhesus monkeys. Therefore, the pharmacokinetics (PK) of cefovecin after a single subcutaneous injection at 8 mg/kg bodyweight in four rhesus monkeys (Macaca mulatta) and sensitivity of bacterial isolates from fresh skin wounds were determined. After administration, blood, urine, and feces were collected, and concentrations of cefovecin were determined. Further, the minimum inhibitory concentrations (MIC) for bacteria isolated from fresh skin wounds of monkeys during a health control program were determined. The mean maximum plasma concentration (C(max) ) of cefovecin was 78 μg/mL and was achieved after 57 min. The mean apparent long elimination half-life (t½) was 6.6 h and excretion occurred mainly via urine. The MIC for the majority of the bacteria examined was >100 μg/mL. The PK of cefovecin in rhesus monkeys is substantially different than for dogs and cats. Cefovecin rapidly reached C(max) which however was lower than most of the MIC levels and with a very short t½. Therefore, cefovecin is not recommended for treating skin wounds in rhesus monkeys. © 2011 Blackwell Publishing Ltd.

  3. Molecular characterization of Blastocystis isolates from children and rhesus monkeys in Kathmandu, Nepal.

    PubMed

    Yoshikawa, Hisao; Wu, Zhiliang; Pandey, Kishor; Pandey, Basu Dev; Sherchand, Jeevan Bahadur; Yanagi, Tetsuo; Kanbara, Hiroji

    2009-03-23

    To investigate the possible transmission of Blastocystis organisms between local rhesus monkeys and children in Kathmandu, Nepal, we compared the subtype (ST) and sequence of Blastocystis isolates from children with gastrointestinal symptoms and local rhesus monkeys. Twenty and 10 Blastocystis isolates were established from 82 and 10 fecal samples obtained from children and monkeys, respectively. Subtype analysis with seven sequence-tagged site (STS) primers indicated that the prevalence of Blastocystis sp. ST1, ST2 and ST3 was 20%, 20% and 60% in the child isolates, respectively. In contrast to human isolates, ST3 was not found in monkey isolates and the prevalence of ST1 and ST2 was 50% and 70%, respectively, including three mixed STs1 and 2 and one isolate not amplified by any STS primers, respectively. Since Blastocystis sp. ST2 has been reported as the most dominant genotype in the survey of Blastocystis infection among the various monkey species, sequence comparison of the 150bp variable region of the small subunit rRNA (SSU rRNA) gene was conducted among ST2 isolates of humans and monkeys. Sequence alignment of 24 clones developed from ST2 isolates of 4 humans and 4 monkeys showed three distinct subgroups, defined as ST2A, ST2B and ST2C. These three subgroups were shared between the child and monkey isolates. These results suggest that the local rhesus monkeys are a possible source of Blastocystis sp. ST2 infection of humans in Kathmandu.

  4. Immunization with Recombinant Helicobacter pylori Urease in Specific-Pathogen-Free Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Solnick, Jay V.; Canfield, Don R.; Hansen, Lori M.; Torabian, Sima Z.

    2000-01-01

    Immunization with urease can protect mice from challenge with Helicobacter pylori, though results vary depending on the particular vaccine, challenge strain, and method of evaluation. Unlike mice, rhesus monkeys are naturally colonized with H. pylori and so may provide a better estimate of vaccine efficacy in humans. The purpose of this study was to examine the effectiveness of H. pylori urease as a vaccine in specific-pathogen (H. pylori)-free rhesus monkeys. Monkeys raised from birth and documented to be free of H. pylori were vaccinated with orogastric (n = 4) or intramuscular (n = 5) urease. Two control monkeys were sham vaccinated. All monkeys were challenged with a rhesus monkey-derived strain of H. pylori, and the effects of vaccination were evaluated by use of quantitative cultures of gastric tissue, histology, and measurement of serum immunoglobulin G (IgG) and salivary IgA. Despite a humoral immune response, all monkeys were infected after H. pylori challenge, and there were no differences in the density of colonization. Immunization with urease therefore does not fully protect against challenge with H. pylori. An effective vaccine to prevent H. pylori infection will require different or more likely additional antigens, as well as improvements in the stimulation of the host immune response. PMID:10768944

  5. Suppurative bite wound by repetitive aggression of dominance hierarchy during group housing in rhesus monkeys.

    PubMed

    Choi, Yunjung; Ahn, Kyung-Ha; Lee, Jae-Il

    2014-12-01

    Group formation of rhesus monkeys, often leads to victims of repeated attacks by the high ranking animal. We reported a case of an injured middle ranking monkey from repetitive and persistent aggression. 4-male rhesus group was formed by a rapid group formation strategy 2 years ago. One monkey in the group suddenly showed depressive and reluctant movement. Physical examination revealed multiple bite wounds and scars in the dorsal skin. Overall increased opacity of the dorsal soft tissue and some free air was observed on radiographic examination. An unidentified anaerobic gram negative bacillus was isolated from the bacterial culture. Reconstructive surgery was performed and in consequence, the wound was clearly reconstructed one week later. Eventually, the afflicted monkey was separated and housed apart from the hierarchical group. This case report indicate that group formation in rhesus monkeys is essentially required sufficient time and stages, as well as more attention and a progressive contact program to reduce animal stress and fatal accidents.

  6. Molecular cloning and characterization of rhesus monkey platelet glycoprotein Ibα, a major ligand-binding subunit of GPIb-IX-V complex.

    PubMed

    Qiao, Jianlin; Shen, Yang; Shi, Meimei; Lu, Yanrong; Cheng, Jingqiu; Chen, Younan

    2014-05-01

    Through binding to von Willebrand factor (VWF), platelet glycoprotein (GP) Ibα, the major ligand-binding subunit of the GPIb-IX-V complex, initiates platelet adhesion and aggregation in response to exposed VWF or elevated fluid-shear stress. There is little data regarding non-human primate platelet GPIbα. This study cloned and characterized rhesus monkey (Macaca Mullatta) platelet GPIbα. DNAMAN software was used for sequence analysis and alignment. N/O-glycosylation sites and 3-D structure modelling were predicted by online OGPET v1.0, NetOGlyc 1.0 Server and SWISS-MODEL, respectively. Platelet function was evaluated by ADP- or ristocetin-induced platelet aggregation. Rhesus monkey GPIbα contains 2,268 nucleotides with an open reading frame encoding 755 amino acids. Rhesus monkey GPIbα nucleotide and protein sequences share 93.27% and 89.20% homology respectively, with human. Sequences encoding the leucine-rich repeats of rhesus monkey GPIbα share strong similarity with human, whereas PEST sequences and N/O-glycosylated residues vary. The GPIbα-binding residues for thrombin, filamin A and 14-3-3ζ are highly conserved between rhesus monkey and human. Platelet function analysis revealed monkey and human platelets respond similarly to ADP, but rhesus monkey platelets failed to respond to low doses of ristocetin where human platelets achieved 76% aggregation. However, monkey platelets aggregated in response to higher ristocetin doses. Monkey GPIbα shares strong homology with human GPIbα, however there are some differences in rhesus monkey platelet activation through GPIbα engagement, which need to be considered when using rhesus monkey platelet to investigate platelet GPIbα function. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Canine Distemper Outbreak in Rhesus Monkeys, China

    PubMed Central

    Qiu, Wei; Zheng, Ying; Zhang, Shoufeng; Fan, Quanshui; Liu, Hua; Zhang, Fuqiang; Wang, Wei; Liao, Guoyang

    2011-01-01

    Since 2006, canine distemper outbreaks have occurred in rhesus monkeys at a breeding farm in Guangxi, People’s Republic of China. Approximately 10,000 animals were infected (25%–60% disease incidence); 5%–30% of infected animals died. The epidemic was controlled by vaccination. Amino acid sequence analysis of the virus indicated a unique strain. PMID:21801646

  8. Allergic asthma induced in rhesus monkeys by house dust mite (Dermatophagoides farinae).

    PubMed

    Schelegle, E S; Gershwin, L J; Miller, L A; Fanucchi, M V; Van Winkle, L S; Gerriets, J P; Walby, W F; Omlor, A M; Buckpitt, A R; Tarkington, B K; Wong, V J; Joad, J P; Pinkerton, K B; Wu, R; Evans, M J; Hyde, D M; Plopper, C G

    2001-01-01

    To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4(+) lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA.

  9. Allergic Asthma Induced in Rhesus Monkeys by House Dust Mite (Dermatophagoides farinae)

    PubMed Central

    Schelegle, Edward S.; Gershwin, Laurel J.; Miller, Lisa A.; Fanucchi, Michelle V.; Van Winkle, Laura S.; Gerriets, Joan P.; Walby, William F.; Omlor, Amanda M.; Buckpitt, Alan R.; Tarkington, Brian K.; Wong, Viviana J.; Joad, Jesse P.; Pinkerton, Kent B.; Wu, Reen; Evans, Michael J.; Hyde, Dallas M.; Plopper, Charles G.

    2001-01-01

    To establish whether allergic asthma could be induced experimentally in a nonhuman primate using a common human allergen, three female rhesus monkeys (Macaca mulatta) were sensitized with house dust mite (Dermatophagoides farinae) allergen (HDMA) by subcutaneous injection, followed by four intranasal sensitizations, and exposure to allergen aerosol 3 hours per day, 3 days per week for up to 13 weeks. Before aerosol challenge, all three monkeys skin-tested positive for HDMA. During aerosol challenge with HDMA, sensitized monkeys exhibited cough and rapid shallow breathing and increased airway resistance, which was reversed by albuterol aerosol treatment. Compared to nonsensitized monkeys, there was a fourfold reduction in the dose of histamine aerosol necessary to produce a 150% increase in airway resistance in sensitized monkeys. After aerosol challenge, serum levels of histamine were elevated in sensitized monkeys. Sensitized monkeys exhibited increased levels of HDMA-specific IgE in serum, numbers of eosinophils and exfoliated cells within lavage, and elevated CD25 expression on circulating CD4+ lymphocytes. Intrapulmonary bronchi of sensitized monkeys had focal mucus cell hyperplasia, interstitial infiltrates of eosinophils, and thickening of the basement membrane zone. We conclude that a model of allergic asthma can be induced in rhesus monkeys using a protocol consisting of subcutaneous injection, intranasal instillation, and aerosol challenge with HDMA. PMID:11141508

  10. Rhesus monkeys (Macaca mulatta) detect rhythmic groups in music, but not the beat.

    PubMed

    Honing, Henkjan; Merchant, Hugo; Háden, Gábor P; Prado, Luis; Bartolo, Ramón

    2012-01-01

    It was recently shown that rhythmic entrainment, long considered a human-specific mechanism, can be demonstrated in a selected group of bird species, and, somewhat surprisingly, not in more closely related species such as nonhuman primates. This observation supports the vocal learning hypothesis that suggests rhythmic entrainment to be a by-product of the vocal learning mechanisms that are shared by several bird and mammal species, including humans, but that are only weakly developed, or missing entirely, in nonhuman primates. To test this hypothesis we measured auditory event-related potentials (ERPs) in two rhesus monkeys (Macaca mulatta), probing a well-documented component in humans, the mismatch negativity (MMN) to study rhythmic expectation. We demonstrate for the first time in rhesus monkeys that, in response to infrequent deviants in pitch that were presented in a continuous sound stream using an oddball paradigm, a comparable ERP component can be detected with negative deflections in early latencies (Experiment 1). Subsequently we tested whether rhesus monkeys can detect gaps (omissions at random positions in the sound stream; Experiment 2) and, using more complex stimuli, also the beat (omissions at the first position of a musical unit, i.e. the 'downbeat'; Experiment 3). In contrast to what has been shown in human adults and newborns (using identical stimuli and experimental paradigm), the results suggest that rhesus monkeys are not able to detect the beat in music. These findings are in support of the hypothesis that beat induction (the cognitive mechanism that supports the perception of a regular pulse from a varying rhythm) is species-specific and absent in nonhuman primates. In addition, the findings support the auditory timing dissociation hypothesis, with rhesus monkeys being sensitive to rhythmic grouping (detecting the start of a rhythmic group), but not to the induced beat (detecting a regularity from a varying rhythm).

  11. Etonitazene as a reinforcer: oral intake of etonitazene by rhesus monkeys.

    PubMed

    Carroll, M E; Meisch, R A

    1978-12-08

    Drinking of etonitazene HCI was studied in three rhesus monkeys during daily 3-h sessions. As the drug concentration was increased, the number of liquid deliveries decreased, and etonitazene intake (microgram/kg body weight) increased. As fixed-ratio (FR) requirements were increased, rate of responding increased, and liquid deliveries slightly decreased. When water was substituted for the drug, there was a large increase in responding for several sessions, followed by a slow decline to low rates. When etonitazene was reintroduced, responding abruptly increased to previous drug levels. These data suggest that etonitazene can serve as a positive reinforcer when taken orally by rhesus monkeys.

  12. Piracetam-induced changes on the brainstem auditory response in anesthetized juvenile rhesus monkeys (Macaca mulatta). Report of two clinical cases.

    PubMed

    Durand-Rivera, A; Gonzalez-Pina, R; Hernandez-Godinez, B; Ibanez-Contreras, A; Bueno-Nava, A; Alfaro-Rodriguez, A

    2012-10-01

    We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. In this report, we discuss the significance of these observations. © 2012 John Wiley & Sons A/S.

  13. Essentialism in the Absence of Language? Evidence from Rhesus Monkeys ("Macaca mulatta")

    ERIC Educational Resources Information Center

    Phillips, Webb; Shankar, Maya; Santos, Laurie R.

    2010-01-01

    We explored whether rhesus monkeys (Macaca mulatta) share one important feature of human essentialist reasoning: the capacity to track category membership across radical featural transformations. Specifically, we examined whether monkeys--like children (Keil, 1989)--expect a transformed object to have the internal properties of its original…

  14. Spontaneous epithelioid hemangiosarcoma in a rhesus monkey (Macaca mulatta).

    PubMed

    Tsuchiya, Takayuki; Gray, Tasha L; Gatto, Nicholas T; Forest, Thomas; Machotka, Sam V; Troth, Sean P; Prahalada, Srinivasa

    2014-08-01

    Epithelioid hemangiosarcoma is a rare malignant endothelial neoplasia with a unique, predominantly epithelioid morphology. A 4-y-old rhesus monkey from our laboratory had multiple neoplastic nodules in a digit, limb skin, hindlimb muscle, and visceral organs including lung, heart, and brain. The nodules were composed of pleomorphic, polygonal, epithelioid, neoplastic cells that were arranged in sheets, nests, and cords and supported by variably dense fibrovascular connective tissue. The morphologic features of this tumor were predominantly epithelioid. However, some regions contained cystic spaces, clefts, and channel-like structures, all of which were lined with morphologically distinct neoplastic endothelial cells. These neoplastic cells, with or without epithelioid morphology, were positive immunohistochemically for CD31, factor VIII-related antigen, and vimentin. The presence of multiple metastatic nodules, high mitotic rate, and extensive Ki67-positive staining were consistent with malignancy. This report is the first description of epithelioid hemangiosarcoma in a rhesus monkey.

  15. Nature of the Refractive Errors in Rhesus Monkeys (Macaca mulatta) with Experimentally Induced Ametropias

    PubMed Central

    Qiao-Grider, Ying; Hung, Li-Fang; Kee, Chea-su; Ramamirtham, Ramkumar; Smith, Earl L.

    2010-01-01

    We analyzed the contribution of individual ocular components to vision-induced ametropias in 210 rhesus monkeys. The primary contribution to refractive-error development came from vitreous chamber depth; a minor contribution from corneal power was also detected. However, there was no systematic relationship between refractive error and anterior chamber depth or between refractive error and any crystalline lens parameter. Our results are in good agreement with previous studies in humans, suggesting that the refractive errors commonly observed in humans are created by vision-dependent mechanisms that are similar to those operating in monkeys. This concordance emphasizes the applicability of rhesus monkeys in refractive-error studies. PMID:20600237

  16. Effect of space flight on cytokine production and other immunologic parameters of rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, G.; Davis, S.; Taylor, G. R.; Mandel, A. D.; Konstantinova, I. V.; Lesnyak, A.; Fuchs, B. B.; Peres, C.; Tkackzuk, J.; Schmitt, D. A.

    1996-01-01

    During a recent flight of a Russian satellite (Cosmos #2229), initial experiments examining the effects of space flight on immunologic responses of rhesus monkeys were performed to gain insight into the effect of space flight on resistance to infection. Experiments were performed on tissue samples taken from the monkeys before and immediately after flight. Additional samples were obtained approximately 1 month after flight for a postflight restraint study. Two types of experiments were carried out throughout this study. The first experiment determined the ability of leukocytes to produce interleukin-1 and to express interleukin-2 receptors. The second experiment examined the responsiveness of rhesus bone marrow cells to recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF). Human reagents that cross-reacted with monkey tissue were utilized for the bulk of the studies. Results from both studies indicated that there were changes in immunologic function attributable to space flight. Interleukin-1 production and the expression of interleukin-2 receptors was decreased after space flight. Bone marrow cells from flight monkeys showed a significant decrease in their response to GM-CSF compared with the response of bone marrow cells from nonflight control monkeys. These results suggest that the rhesus monkey may be a useful surrogate for humans in future studies that examine the effect of space flight on immune response, particularly when conditions do not readily permit human study.

  17. Pathogenesis of Rift Valley Fever in Rhesus Monkeys: Role of Interferon Response

    DTIC Science & Technology

    1990-01-01

    hemorrhagic fever characterized by epistaxis, petechial to purpuric cutaneous lesions, anorexia, and vomiting prior to death. The 14 remaining monkeys survived...DMI, FILE Copy Arch Virol (1990) 110: 195-212 Amhivesirology ( by Springer-Verlag 1990 00 N Pathogenesis of Rift Valley fever in rhesus monkeys: (NI...inoculated intravenously with Rift Valley fever (RVF) virus presented clinical disease syndromes similar to human cases of RVF. All 17 infected monkeys

  18. Spontaneous Epithelioid Hemangiosarcoma in a Rhesus Monkey (Macaca mulatta)

    PubMed Central

    Tsuchiya, Takayuki; Gray, Tasha L; Gatto, Nicholas T; Forest, Thomas; Machotka, Sam V; Troth, Sean P; Prahalada, Srinivasa

    2014-01-01

    Epithelioid hemangiosarcoma is a rare malignant endothelial neoplasia with a unique, predominantly epithelioid morphology. A 4-y-old rhesus monkey from our laboratory had multiple neoplastic nodules in a digit, limb skin, hindlimb muscle, and visceral organs including lung, heart, and brain. The nodules were composed of pleomorphic, polygonal, epithelioid, neoplastic cells that were arranged in sheets, nests, and cords and supported by variably dense fibrovascular connective tissue. The morphologic features of this tumor were predominantly epithelioid. However, some regions contained cystic spaces, clefts, and channel-like structures, all of which were lined with morphologically distinct neoplastic endothelial cells. These neoplastic cells, with or without epithelioid morphology, were positive immunohistochemically for CD31, factor VIII-related antigen, and vimentin. The presence of multiple metastatic nodules, high mitotic rate, and extensive Ki67-positive staining were consistent with malignancy. This report is the first description of epithelioid hemangiosarcoma in a rhesus monkey. PMID:25296017

  19. Social stimuli enhance phencyclidine (PCP) self-administration in rhesus monkeys

    PubMed Central

    Newman, Jennifer L.; Perry, Jennifer L.; Carroll, Marilyn E.

    2007-01-01

    Environmental factors, including social interaction, can alter the effects of drugs of abuse on behavior. The present study was conducted to examine the effects of social stimuli on oral phencyclidine (PCP) self-administration by rhesus monkeys. Ten adult rhesus monkeys (M. mulatta) were housed side by side in modular cages that could be configured to provide visual, auditory, and olfactory stimuli provided by another monkey located in the other side of the paired unit. During the first experiment, monkeys self-administered PCP (0.25 mg/ml) and water under concurrent fixed ratio (FR) 16 schedules of reinforcement with either a solid or a grid (social) partition separating each pair of monkeys. In the second experiment, a PCP concentration-response relationship was determined under concurrent progressive ratio (PR) schedules of reinforcement under the solid and grid partition conditions. Under the concurrent FR 16 schedules, PCP and water self-administration was significantly higher during exposure to a cage mate through a grid partition than when a solid partition separated the monkeys. The relative reinforcing strength of PCP, as measured by PR break points, was greater during the grid partition condition compared to the solid partition condition indicated by an upward shift in the concentration-response curve. To determine whether the social stimuli provided by another monkey led to activation of the hypothalamic-pituitary-adrenal (HPA) axis, which may have evoked the increase of PCP self-administration during the grid partition condition, a third experiment was conducted to examine cortisol levels under the two housing conditions. A modest, but nonsignificant increase in cortisol levels was found upon switching from the solid to the grid partition condition. The results suggest that social stimulation among monkeys in adjoining cages leads to enhanced reinforcing strength of PCP. PMID:17560636

  20. Evaluation of seven hypotheses for metamemory performance in rhesus monkeys

    PubMed Central

    Basile, Benjamin M.; Schroeder, Gabriel R.; Brown, Emily Kathryn; Templer, Victoria L.; Hampton, Robert R.

    2014-01-01

    Knowing the extent to which nonhumans and humans share mechanisms for metacognition will advance our understanding of cognitive evolution and will improve selection of model systems for biomedical research. Some nonhuman species avoid difficult cognitive tests, seek information when ignorant, or otherwise behave in ways consistent with metacognition. There is agreement that some nonhuman animals “succeed” in these metacognitive tasks, but little consensus about the cognitive mechanisms underlying performance. In one paradigm, rhesus monkeys visually searched for hidden food when ignorant of the location of the food, but acted immediately when knowledgeable. This result has been interpreted as evidence that monkeys introspectively monitored their memory to adaptively control information seeking. However, convincing alternative hypotheses have been advanced that might also account for the adaptive pattern of visual searching. We evaluated seven hypotheses using a computerized task in which monkeys chose either to take memory tests immediately or to see the answer again before proceeding to the test. We found no evidence to support the hypotheses of behavioral cue association, rote response learning, expectancy violation, response competition, generalized search strategy, or postural mediation. In contrast, we repeatedly found evidence to support the memory monitoring hypothesis. Monkeys chose to see the answer when memory was poor, either from natural variation or experimental manipulation. We found limited evidence that monkeys also monitored the fluency of memory access. Overall, the evidence indicates that rhesus monkeys can use memory strength as a discriminative cue for information seeking, consistent with introspective monitoring of explicit memory. PMID:25365530

  1. [Vaccination of rhesus monkeys with recombinant antigen fragments and protection from hepatitis E virus infection].

    PubMed

    Ma, Yan-bing; Xie, Tian-hong; Zhang, Guang-ming; Li, Chun-hong; Dai, Xie-Jie; Dai, Chang-bai; Sun, Mao-sheng; Lu, Jian; Bi, Sheng-li

    2002-12-01

    To observe anti-HEV IgG response to vaccination of recombinant antigen fragments and evaluate its protection from Hepatitis E Virus infection in rhesus monkeys (Macaca mulatta). Twelve monkeys were divided into three groups and immunized respectively with three different recombinant antigens: namely Ag1 (carboxyl terminal 431 amino acids of ORF2), Ag2 (128aa fragment at the carboxyl terminal of ORF2), and Ag3 (full length ORF3 ligated with two ORF2 fragments encoded by 6743-7126nt and 6287-6404nt). The monkeys were challenged intravenously with fecal suspension from experimentally infected rhesus monkeys, and the other three monkeys served as the placebo group for challenge with HEV. The dynamic changes of the levels of ALT and anti-HEV IgG were examined. Pathological changes of liver tissue were observed by light microscope. Excretion of virus was detected by RT-nPCR. Hepatic histopathology of two monkeys in the placebo group was consistent with acute viral hepatitis, and ALT was elevated 3-4 weeks after inoculated with virus, up to 10-20 times higher than normal level. The liver tissue of monkeys immunized with antigen kept normal, ALT in several monkeys elevated mildly, and anti-HEV IgG conversation occurred at 1-2 weeks after vaccination, with the titer reaching 1:12,800. The virus RNA could be detected by RT-nPCR from days 7 to 50 in monkeys of control group, and from days 7 to 21 in vaccinated monkeys after challenged with virus. The recombinant antigens could induce the production of anti-HEV IgG, which protected rhesus monkeys from acute Hepatitis symptoms related to HEV infection.

  2. Nature of the refractive errors in rhesus monkeys (Macaca mulatta) with experimentally induced ametropias.

    PubMed

    Qiao-Grider, Ying; Hung, Li-Fang; Kee, Chea-Su; Ramamirtham, Ramkumar; Smith, Earl L

    2010-08-23

    We analyzed the contribution of individual ocular components to vision-induced ametropias in 210 rhesus monkeys. The primary contribution to refractive-error development came from vitreous chamber depth; a minor contribution from corneal power was also detected. However, there was no systematic relationship between refractive error and anterior chamber depth or between refractive error and any crystalline lens parameter. Our results are in good agreement with previous studies in humans, suggesting that the refractive errors commonly observed in humans are created by vision-dependent mechanisms that are similar to those operating in monkeys. This concordance emphasizes the applicability of rhesus monkeys in refractive-error studies. Copyright 2010 Elsevier Ltd. All rights reserved.

  3. Do rhesus monkeys (Macaca mulatta) perceive illusory motion?

    PubMed

    Agrillo, Christian; Gori, Simone; Beran, Michael J

    2015-07-01

    During the last decade, visual illusions have been used repeatedly to understand similarities and differences in visual perception of human and non-human animals. However, nearly all studies have focused only on illusions not related to motion perception, and to date, it is unknown whether non-human primates perceive any kind of motion illusion. In the present study, we investigated whether rhesus monkeys (Macaca mulatta) perceived one of the most popular motion illusions in humans, the Rotating Snake illusion (RSI). To this purpose, we set up four experiments. In Experiment 1, subjects initially were trained to discriminate static versus dynamic arrays. Once reaching the learning criterion, they underwent probe trials in which we presented the RSI and a control stimulus identical in overall configuration with the exception that the order of the luminance sequence was changed in a way that no apparent motion is perceived by humans. The overall performance of monkeys indicated that they spontaneously classified RSI as a dynamic array. Subsequently, we tested adult humans in the same task with the aim of directly comparing the performance of human and non-human primates (Experiment 2). In Experiment 3, we found that monkeys can be successfully trained to discriminate between the RSI and a control stimulus. Experiment 4 showed that a simple change in luminance sequence in the two arrays could not explain the performance reported in Experiment 3. These results suggest that some rhesus monkeys display a human-like perception of this motion illusion, raising the possibility that the neurocognitive systems underlying motion perception may be similar between human and non-human primates.

  4. Assessing Unit-Price Related Remifentanil Choice in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Galuska, Chad M.; Winger, Gail; Woods, James H.; Hursh, Steven R.

    2006-01-01

    Given a commodity available at different prices, a unit-price account of choice predicts preference for the cheaper alternative. This experiment determined if rhesus monkeys preferred remifentanil (an ultra-short-acting [mu]-opioid agonist) delivered at a lower unit price over a higher-priced remifentanil alternative (Phases 1 and 3). Choice…

  5. Perceived control in rhesus monkeys (Macaca mulatta) - Enhanced video-task performance

    NASA Technical Reports Server (NTRS)

    Washburn, David A.; Hopkins, William D.; Rumbaugh, Duane M.

    1991-01-01

    This investigation was designed to determine whether perceived control effects found in humans extend to rhesus monkeys (Macaca mulatta) tested in a video-task format, using a computer-generated menu program, SELECT. Choosing one of the options in SELECT resulted in presentation of five trials of a corresponding task and subsequent return to the menu. In Experiments 1-3, the animals exhibited stable, meaningful response patterns in this task (i.e., they made choices). In Experiment 4, performance on tasks that were selected by the animals significantly exceeded performance on identical tasks when assigned by the experimenter under comparable conditions (e.g., time of day, order, variety). The reliable and significant advantage for performance on selected tasks, typically found in humans, suggests that rhesus monkeys were able to perceive the availability of choices.

  6. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine

    PubMed Central

    Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

    2016-01-01

    Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species. PMID:27479072

  7. Characterization of the Sweet Taste Receptor Tas1r2 from an Old World Monkey Species Rhesus Monkey and Species-Dependent Activation of the Monomeric Receptor by an Intense Sweetener Perillartine.

    PubMed

    Cai, Chenggu; Jiang, Hua; Li, Lei; Liu, Tianming; Song, Xuejie; Liu, Bo

    2016-01-01

    Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates. Furthermore, similar to human TAS1R2, rhesus monkey Tas1r2 could respond to artificial sweeteners and sweet-tasting proteins. However, the responses induced by rhesus monkey Tas1r2 could not be inhibited by the sweet inhibitor amiloride. Moreover, we found a species-dependent activation of the Tas1r2 monomeric receptors of human, rhesus monkey and squirrel monkey but not mouse by an intense sweetener perillartine. Molecular modeling and sequence analysis indicate that the receptor has the conserved domains and ligand-specific interactive residues, which have been identified in the characterized sweet taste receptors up to now. This is the first report of the functional characterization of sweet taste receptors from an Old World monkey species.

  8. An attempt to eradicate Herpesvirus simiae from a rhesus monkey breeding colony.

    PubMed

    Sauber, J J; Fanton, J W; Harvey, R C; Golden, J G

    1992-10-01

    In the fall of 1987 an attempt to establish a Herpesvirus simiae (B-virus)-negative rhesus monkey (Macaca mulatta) breeding colony was initiated at the Armstrong Laboratory. A serologic testing program was used to identify all monkeys into groups that were either positive or negative to B-virus based on serologic tests. Segregation of the groups allowed the creation of breeding harems that were exclusively seropositive or -negative to B-virus. Animals that were serologically positive were kept in breeding to maintain infant production levels not unlike those previous to segregation. Decreasing numbers of animals converted to a positive status during the first three serum tests for B-virus in the program. During 1990, an increase in the number of monkeys converting to positive status and the discovery of an indeterminate status demonstrated that latency of B-virus in the rhesus may have the potential to defeat an eradication attempt not conscientiously pursued.

  9. Lack of cleavage of immunoglobulin A (IgA) from rhesus monkeys by bacterial IgA1 proteases.

    PubMed Central

    Reinholdt, J; Kilian, M

    1991-01-01

    Bacterial immunoglobulin A1 (IgA1) proteases cleaving IgA1 and secretory IgA1 molecules in the hinge region are believed to be important virulence factors. Previous studies have indicated that IgA of humans, gorillas, and chimpanzees are the exclusive substrates of these enzymes. In a recent study, IgA from the rhesus monkey was found to be susceptible to the IgA1 protease activity of Streptococcus pneumoniae. In an attempt to reproduce this observation, we found that neither five isolates of S. pneumoniae nor other IgA1 protease-producing bacteria representing different cleavage specificities caused cleavage of rhesus monkey IgA. Hence, the rhesus monkey does not appear to be a suitable animal model for studies of IgA1 proteases as virulence factors. Images PMID:2037384

  10. Use of a Recombinant Gamma-2 Herpesvirus Vaccine Vector against Dengue Virus in Rhesus Monkeys.

    PubMed

    Bischof, Georg F; Magnani, Diogo M; Ricciardi, Michael; Shin, Young C; Domingues, Aline; Bailey, Varian K; Gonzalez-Nieto, Lucas; Rakasz, Eva G; Watkins, David I; Desrosiers, Ronald C

    2017-08-15

    Research on vaccine approaches that can provide long-term protection against dengue virus infection is needed. Here we describe the construction, immunogenicity, and preliminary information on the protective capacity of recombinant, replication-competent rhesus monkey rhadinovirus (RRV), a persisting herpesvirus. One RRV construct expressed nonstructural protein 5 (NS5), while a second recombinant expressed a soluble variant of the E protein (E85) of dengue virus 2 (DENV2). Four rhesus macaques received a single vaccination with a mixture of both recombinant RRVs and were subsequently challenged 19 weeks later with 1 × 10 5 PFU of DENV2. During the vaccine phase, plasma of all vaccinated monkeys showed neutralizing activity against DENV2. Cellular immune responses against NS5 were also elicited, as evidenced by major histocompatibility complex class I (MHC-I) tetramer staining in the one vaccinated monkey that was Mamu-A*01 positive. Unlike two of two unvaccinated controls, two of the four vaccinated monkeys showed no detectable viral RNA sequences in plasma after challenge. One of these two monkeys also showed no anamnestic increases in antibody levels following challenge and thus appeared to be protected against the acquisition of DENV2 following high-dose challenge. Continued study will be needed to evaluate the performance of herpesviral and other persisting vectors for achieving long-term protection against dengue virus infection. IMPORTANCE Continuing studies of vaccine approaches against dengue virus (DENV) infection are warranted, particularly ones that may provide long-term immunity against all four serotypes. Here we investigated whether recombinant rhesus monkey rhadinovirus (RRV) could be used as a vaccine against DENV2 infection in rhesus monkeys. Upon vaccination, all animals generated antibodies capable of neutralizing DENV2. Two of four vaccinated monkeys showed no detectable viral RNA after subsequent high-dose DENV2 challenge at 19 weeks

  11. Rhesus Monkeys (Macaca Mulatta) Maintain Learning Set Despite Second-Order Stimulus-Response Spatial Discontiguity

    ERIC Educational Resources Information Center

    Beran, Michael J.; Washburn, David A.; Rumbaugh, Duane M.

    2007-01-01

    In many discrimination-learning tests, spatial separation between stimuli and response loci disrupts performance in rhesus macaques. However, monkeys are unaffected by such stimulus-response spatial discontiguity when responses occur through joystick-based computerized movement of a cursor. To examine this discrepancy, five monkeys were tested on…

  12. Vestibular functions and sleep in space experiments. [using rhesus and owl monkeys

    NASA Technical Reports Server (NTRS)

    Perachio, A. A.

    1977-01-01

    Physical indices of sleep were continuously monitored in an owl monkey living in a chamber continuously rotating at a constant angular velocity. The electrophysiological data obtained from chronically implanted electrodes was analyzed to determine the chronic effects of vestibular stimulation on sleep and wakefulness cycles. The interaction of linear and angular acceleration on the vestibulo-ocular reflex was investigated in three rhesus monkeys at various angular accelerations.

  13. Investigations of rhesus monkey video-task performance: evidence for enrichment

    NASA Technical Reports Server (NTRS)

    Washburn, D. A.; Rumbaugh, D. M.

    1992-01-01

    We have developed the Language Research Center's Computerized Test System (LRC-CTS) for psychological research. Basically, the LRC-CTS is a battery of software tasks--computerized versions of many of the classic testing paradigms of cognitive and comparative psychology--and the hardware required to administer them. An XT- or 386-compatible computer is connected to a color monitor, onto which computer-generated stimuli are presented. Sound feedback is delivered through an external speaker/amplifier, and a joystick is used as an input device. The animals reach through the mesh of their home cages to manipulate the joystick, which causes isomorphic movements of a cursor on the screen thereby allowing animals to respond according to the varied demands of the tasks. Correct responses are rewarded with a fruit-flavored chow pellet. Using this technology, we have trained and tested rhesus monkeys, a variety of apes, human adults, and normally developing or mentally retarded human children. Other labs using the LRC-CTS are beginning to report encouraging results with other monkey species as well. From this research, a number of interesting and important psychological findings have resulted. In the present paper, however, evidence will be reviewed which suggests that the LRC-CTS is an effective means of providing environmental enrichment to singly housed rhesus monkeys.

  14. Persistent infection of rhesus monkeys with 'Helicobacter macacae' and its isolation from an animal with intestinal adenocarcinoma.

    PubMed

    Marini, Robert P; Muthupalani, Sureshkumar; Shen, Zeli; Buckley, Ellen M; Alvarado, Cynthia; Taylor, Nancy S; Dewhirst, Floyd E; Whary, Mark T; Patterson, Mary M; Fox, James G

    2010-08-01

    A novel helicobacter, 'Helicobacter macacae', was previously isolated from a colony of rhesus and cynomolgus monkeys in which diarrhoea from chronic idiopathic colitis was enzootic. A survey performed in a second colony of rhesus monkeys without a history of chronic diarrhoea determined that 57 % were faecal-culture positive for Helicobacter species. Ten years after the survey, one of the animals from which 'H. macacae' had been isolated, a 23-year-old, intact male rhesus monkey (Macaca mulatta), presented with partial inappetence and progressive weight loss. Subsequent evaluation of the monkey revealed anaemia, hypoproteinaemia, hypoalbuminaemia and a palpable abdominal mass. Contrast radiography suggested partial intestinal obstruction. The animal was euthanized and a diagnosis was made of intestinal adenocarcinoma of the ileocaecocolic junction with metastasis to regional lymph nodes and liver. Microaerobic culture of caecal tissue yielded a helicobacter organism identified as 'H. macacae' by 16S rRNA gene sequencing - the same species of bacteria isolated 10 years previously. The liver, small intestine and colon were also positive by PCR for Helicobacter species. Intestinal adenocarcinoma is the most common malignancy of aged macaques. Faeces or caecal tissue from five out of five monkeys that remained from the original cohort and that were colonized with 'H. macacae' in the initial survey were positive for the organism. The apparent persistence of 'H. macacae' in these animals, the isolation of the bacterium from animals with colitis and the recognition of the importance of inflammation in carcinogenesis raise the possibility of an aetiological role in the genesis of intestinal adenocarcinoma in aged rhesus monkeys.

  15. Infection and persistence of rhesus monkey rhadinovirus in immortalized B-cell lines.

    PubMed

    Bilello, John P; Lang, Sabine M; Wang, Fred; Aster, Jon C; Desrosiers, Ronald C

    2006-04-01

    Similar to its close relative human herpesvirus 8, rhesus monkey rhadinovirus (RRV) persists predominantly in B cells of its natural host. Rhesus monkey B-cell lines immortalized by the Epstein-Barr-related virus from rhesus monkeys (rhEBV) were used as targets for infection by RRV. These cultured B cells were susceptible to infection by RRV and continued to produce low titers of RRV for months of continuous culture. Infection by RRV did not detectably alter the growth rates of these B-cell lines when it was measured at standard or reduced serum concentrations. Depending on the cell line, 5 to 40% of the B cells stained positive for the RRV genome by fluorescence in situ hybridization (FISH). Most RRV-positive cells showed a fine punctate nuclear staining pattern consistent with latent infection, while a small minority of cells (0.2 to 1%) contained large, intensely staining nuclear foci consistent with productive, replicative infection. Greater than 90% of the cells were rhEBV genome positive in a pattern consistent with latent infection, and again only a small minority of cells showed a productive, replicative staining pattern. Dual, two-color FISH staining revealed coinfection of numerous cells with both RRV and rhEBV, but productive replication of RRV and rhEBV was always observed in separate cells, never in the same cell. Thus, productive replication of RRV is unlinked to that of rhEBV; factors that influence activation to productive replication act separately on RRV and rhEBV, even within the same cell. The percentage of B cells expressing green fluorescent protein (GFP) early after infection with a recombinant RRV containing a GFP reporter gene was dose dependent and at a low multiplicity of infection increased progressively over time until 14 to 17 days after infection. These results establish a naturalistic cell culture system for the study of infection and persistence by RRV in rhesus monkey B cells.

  16. In Vitro Interleukin-1 and 2 Production and Interleukin 2 Receptor Expression in the Rhesus Monkey

    NASA Technical Reports Server (NTRS)

    Schmitt, Didier A.; Sonnenfeld, Gerald; Husson, David; Tkaczuk, Jean; Andre, Eric; Schaffar, Laurance

    1996-01-01

    Anti-human monoclonal antibodies were used to detect and quantify interleukins-1 and 2 and interleukin-2 receptor expression in peripheral blood mononuclear cells from a rhesus monkey. Interleukin-1 production could be induced by phorbol esters (PMA) and was potentiated by phytohemagglutinin (PHA). Interleukin-2 secretion could also be induced by the combination of PHA and PMA, but only weakly with PHA alone. Interleukin-2 receptor expression was present in a subpopulation of unstimulated lymphocytes and could be enhanced by PHA or PMA. These data show once again that the rhesus monkey immune system is cross-reactive with the human one and that rhesus macaque could be a good model to study interleukin therapy.

  17. Pharmacological evaluation of narcotic antagonist delivery systems in rhesus monkeys.

    PubMed

    Harrigan, S E; Downs, D A

    1981-01-01

    Rhesus monkeys were chronically restrained, intravenously catheterized, and allowed to self-administer morphine, methamphetamine, and saline. Various sustained-release systems containing naltrexone were then implanted in the animals and examined for selective morphine blockade. Similarly, continuous intravenous infusions of naltrexone, buprenorphine, and methadone were tested against morphine or heroin self-administration.

  18. Nonclassical MHC-E (Mamu-E) expression in the rhesus monkey placenta

    PubMed Central

    Dambaeva, Svetlana V.; Bondarenko, Gennadiy I.; Grendell, Richard L.; Kravitz, Rachel H.; Durning, Maureen; Golos, Thaddeus G.

    2009-01-01

    The aim of this study was to characterize the expression of the rhesus HLA-E ortholog Mamu-E, particularly at the maternal-fetal interface. Mamu-E expression was confirmed by locus-specific RT-PCR in the placenta as well as in peripheral blood mononuclear cells (PBMC) and other organs. We evaluated the utility of antibodies recognizing HLA-E (MEM-E/06 against native HLA-E, MEM-E/02 against denatured HLA-E) to detect Mamu-E by flow cytometry/immunofluorescence, Western blot, and immunohistochemistry (IHC). Western blot analysis of cells and selected transfectants confirmed the recognition of Mamu-E but not Mamu-AG by antibodies MEM-E/06 and HC10 but not MEM-E/02. Immunohistochemical staining of frozen sections of rhesus placenta with the MEM-E/06 antibody demonstrated expression in most populations of rhesus monkey trophoblast cells, including villous cytotrophoblasts (strong positive staining), apical membrane of syncytiotrophoblasts (light to moderate staining) and extravillous cytotrophoblasts (moderate to strong staining, especially endovascular trophoblasts in early pregnancy). Expression was not trophoblast cell-specific, especially at term, when endothelial cells in both the chorionic plate and placental villi showed strong staining for Mamu-E. Staining of rhesus extravillous trophoblast cells suggested the co-expression of Mamu-E and Mamu-AG (the rhesus HLA-G homolog) on these cells. MEM-E/06 was shown also to react with differentiating rhesus placental syncytiotrophoblasts in primary culture, detecting intracellular and weak surface expression of Mamu-E. We conclude that the gestation-dependent co-expression of Mamu-E with Mamu-AG in villous and extravillous trophoblast cells suggests important and perhaps complementary but distinct roles of these two nonclassical MHC class I loci in pregnancy at the maternal-fetal interface. In addition, the MEM-E/06 antibody will be useful for the detection of Mamu-E at the maternal-fetal interface in the rhesus monkey

  19. EFFECTS OF PCB (AROCLORR 1254) ON NON-SPECIFIC IMMUNE PARAMETERS IN RHESUS (MACACA MULATA) MONKEYS.

    EPA Science Inventory

    The effects of low level chronic polychlorinated biphenyl - Aroclor 1254 - (PCB) exposure were investigated on nonspecific immune parameters in female rhesus (Macaca mulatta) monkeys. Five groups of monkeys were orally administered PCB at concentrations of 0, 5, 20, 40, or 80 ug/...

  20. Effects of phencyclidine, secobarbital and diazepam on eye tracking in rhesus monkeys.

    PubMed

    Ando, K; Johanson, C E; Levy, D L; Yasillo, N J; Holzman, P S; Schuster, C R

    1983-01-01

    Rhesus monkeys were trained to track a moving disk using a procedure in which responses on a lever were reinforced with water delivery only when the disk, oscillating in a horizontal plane on a screen at a frequency of 0.4 Hz in a visual angle of 20 degrees, dimmed for a brief period. Pursuit eye movements were recorded by electrooculography (EOG). IM phencyclidine, secobarbital, and diazepam injections decreased the number of reinforced lever presses in a dose-related manner. Both secobarbital and diazepam produced episodic jerky-pursuit eye movements, while phencyclidine had no consistent effects on eye movements. Lever pressing was disrupted at doses which had little effect on the quality of smooth-pursuit eye movements in some monkeys. This separation was particularly pronounced with diazepam. The similarities of the drug effects on smooth-pursuit eye movements between the present study and human studies indicate that the present method using rhesus monkeys may be useful for predicting drug effects on eye tracking and oculomotor function in humans.

  1. RHESUS MONKEY - SAM - POSTFLIGHT - LITTLE JOE II (LJ-2) SPACECRAFT

    NASA Image and Video Library

    1963-10-23

    S63-19199 (4 Dec. 1959) --- Sam, the Rhesus monkey, and his handler after his ride in the Little Joe 2 (LJ-2) spacecraft. He is still encased in his contour couch. A U.S. Navy destroyer safely recovered Sam after he experienced three minutes of weightlessness during the flight. Photo credit: NASA

  2. Kinematics of reaching and implications for handedness in rhesus monkey infants

    PubMed Central

    Nelson, Eliza L.; Konidaris, George D.; Berthier, Neil E.; Braun, Maurine C.; Novak, Matthew F.S.X.; Suomi, Stephen J.; Novak, Melinda A.

    2014-01-01

    Kinematic studies of reaching in human infants using two-dimensional (2-D) and three-dimensional (3-D) recordings have complemented behavioral studies of infant handedness by providing additional evidence of early right asymmetries. Right hand reaches have been reported to be straighter and smoother than left hand reaches during the first year. Although reaching has been a popular measure of handedness in primates, there has been no systematic comparison of left and right hand reach kinematics. We investigated reaching in infant rhesus monkeys using the 2-D motion analysis software MaxTRAQ Lite+ (Innovision Systems). Linear mixed-effects models revealed that left hand reaches were smoother, but not straighter, than right hand reaches. An early left bias matches previous findings of a left hand preference for reaching in adult rhesus monkeys. Additional work using this kind of kinematic approach will extend our understanding of primate handedness beyond traditional studies measuring only frequency or bouts of hand use. PMID:22031459

  3. Moderate Level Alcohol During Pregnancy, Prenatal Stress, or Both and Limbic-Hypothalamic-Pituitary-Adrenocortical Axis Response to Stress in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Schneider, Mary L.; Moore, Colleen F.; Kraemer, Gary W.

    2004-01-01

    This study examined the relationship between moderate-level prenatal alcohol exposure, prenatal stress, and postnatal response to a challenging event in 6-month-old rhesus monkeys. Forty-one rhesus monkey (Macaca mulatta) infants were exposed prenatally to moderate level alcohol, maternal stress, or both. Offspring plasma cortisol and…

  4. An assessment of domain-general metacognitive responding in rhesus monkeys.

    PubMed

    Brown, Emily Kathryn; Templer, Victoria L; Hampton, Robert R

    2017-02-01

    Metacognition is the ability to monitor and control one's cognition. Monitoring may involve either public cues or introspection of private cognitive states. We tested rhesus monkeys (Macaca mulatta) in a series of generalization tests to determine which type of cues control metacognition. In Experiment 1, monkeys learned a perceptual discrimination in which a "decline-test" response allowed them to avoid tests and receive a guaranteed small reward. Monkeys declined more difficult than easy tests. In Experiments 2-4, we evaluated whether monkeys generalized this metacognitive responding to new perceptual tests. Monkeys showed a trend toward generalization in Experiments 2 & 3, and reliable generalization in Experiment 4. In Experiments 5 & 6, we presented the decline-test response in a delayed matching-to-sample task. Memory tests differed from perceptual tests in that the appearance of the test display could not control metacognitive responding. In Experiment 6, monkeys made prospective metamemory judgments before seeing the tests. Generalization across perceptual tests with different visual properties and mixed generalization from perceptual to memory tests provide provisional evidence that domain-general, private cues controlled metacognition in some monkeys. We observed individual differences in generalization, suggesting that monkeys differ in use of public and private metacognitive cues. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Visualizing Collagen Network Within Human and Rhesus Monkey Vocal Folds Using Polarized Light Microscopy

    PubMed Central

    Julias, Margaret; Riede, Tobias; Cook, Douglas

    2014-01-01

    Objectives Collagen fiber content and orientation affect the viscoelastic properties of the vocal folds, determining oscillation characteristics during speech and other vocalization. The investigation and reconstruction of the collagen network in vocal folds remains a challenge, because the collagen network requires at least micron-scale resolution. In this study, we used polarized light microscopy to investigate the distribution and alignment of collagen fibers within the vocal folds. Methods Data were collected in sections of human and rhesus monkey (Macaca mulatta) vocal folds cut at 3 different angles and stained with picrosirius red. Results Statistically significant differences were found between different section angles, implying that more than one section angle is required to capture the network’s complexity. In the human vocal folds, the collagen fiber distribution continuously varied across the lamina propria (medial to lateral). Distinct differences in birefringence distribution were observed between the species. For the human vocal folds, high birefringence was observed near the thyroarytenoid muscle and near the epithelium. However, in the rhesus monkey vocal folds, high birefringence was observed near the epithelium, and lower birefringence was seen near the thyroarytenoid muscle. Conclusions The differences between the collagen networks in human and rhesus monkey vocal folds provide a morphological basis for differences in viscoelastic properties between species. PMID:23534129

  6. Peripheral refraction in normal infant rhesus monkeys

    PubMed Central

    Hung, Li-Fang; Ramamirtham, Ramkumar; Huang, Juan; Qiao-Grider, Ying; Smith, Earl L.

    2008-01-01

    Purpose To characterize peripheral refractions in infant monkeys. Methods Cross-sectional data for horizontal refractions were obtained from 58 normal rhesus monkeys at 3 weeks of age. Longitudinal data were obtained for both the vertical and horizontal meridians from 17 monkeys. Refractive errors were measured by retinoscopy along the pupillary axis and at eccentricities of 15, 30, and 45 degrees. Axial dimensions and corneal power were measured by ultrasonography and keratometry, respectively. Results In infant monkeys, the degree of radial astigmatism increased symmetrically with eccentricity in all meridians. There were, however, initial nasal-temporal and superior-inferior asymmetries in the spherical-equivalent refractive errors. Specifically, the refractions in the temporal and superior fields were similar to the central ametropia, but the refractions in the nasal and inferior fields were more myopic than the central ametropia and the relative nasal field myopia increased with the degree of central hyperopia. With age, the degree of radial astigmatism decreased in all meridians and the refractions became more symmetrical along both the horizontal and vertical meridians; small degrees of relative myopia were evident in all fields. Conclusions As in adult humans, refractive error varied as a function of eccentricity in infant monkeys and the pattern of peripheral refraction varied with the central refractive error. With age, emmetropization occurred for both central and peripheral refractive errors resulting in similar refractions across the central 45 degrees of the visual field, which may reflect the actions of vision-dependent, growth-control mechanisms operating over a wide area of the posterior globe. PMID:18487366

  7. Rhesus monkey (Macaca mulatta) complex learning skills reassessed

    NASA Technical Reports Server (NTRS)

    Washburn, David A.; Rumbaugh, Duane M.

    1991-01-01

    An automated computerized testing facility is employed to study basic learning and transfer in rhesus monkeys including discrimination learning set and mediational learning. The data show higher performance levels than those predicted from other tests that involved compromised learning with analogous conditions. Advanced transfer-index ratios and positive transfer of learning are identified, and indications of mediational learning strategies are noted. It is suggested that these data are evidence of the effectiveness of the present experimental apparatus for enhancing learning in nonhuman primates.

  8. A MEG investigation of somatosensory processing in the rhesus monkey

    PubMed Central

    Wilson, Tony W.; Godwin, Dwayne W.; Czoty, Paul W.; Nader, Michael A.; Kraft, Robert A.; Buchheimer, Nancy C.; Daunais, James B.

    2009-01-01

    The use of minimally and non-invasive neuroimaging methods in animal models has sharply increased over the past decade. Such studies have enhanced understanding of the neural basis of the physical signals quantified by these tools, and have addressed an assortment of fundamental and otherwise intractable questions in neurobiology. To date, these studies have almost exclusively utilized positron-emission tomography or variants of magnetic resonance based imaging. These methods provide largely indirect measures of brain activity and are strongly reliant on intact vasculature and normal blood flow, which is known to be compromised in many clinical conditions. The current study provides the first demonstration of whole-head magnetoencephalography (MEG), a non-invasive and direct measure of neuronal activity, in a rhesus monkey, and in the process supplies the initial data on systems-level dynamics in somatosensory cortices. An adult rhesus monkey underwent three separate studies of tactile stimulation on the pad of the right second or fifth digit as whole-head MEG data were acquired. The neural generators of the primary neuromagnetic components were localized using an equivalent-current-dipole model. Second digit stimulation produced an initial cortical response peaking ∼16 ms after stimulus onset in the contralateral somatosensory cortices, with a later response at ∼96 ms in an overlapping or nearby neural area with a roughly orthogonal orientation. Stimulation of the fifth digit produced similar results, the main exception being a substantially weaker later response. We believe the 16ms response is likely the monkey homologue of the human M50 response, as both are the earliest cortical response and localize to the contralateral primary somatosensory area. Thus, these data suggest that mechanoreception in nonhuman primates operates substantially faster than that in adult humans. More broadly, these results demonstrate that it is feasible to use current human whole

  9. Persistent infection of rhesus monkeys with ‘Helicobacter macacae’ and its isolation from an animal with intestinal adenocarcinoma

    PubMed Central

    Marini, Robert P.; Muthupalani, Sureshkumar; Shen, Zeli; Buckley, Ellen M.; Alvarado, Cynthia; Taylor, Nancy S.; Dewhirst, Floyd E.; Whary, Mark T.; Patterson, Mary M.; Fox, James G.

    2010-01-01

    A novel helicobacter, ‘Helicobacter macacae’, was previously isolated from a colony of rhesus and cynomolgus monkeys in which diarrhoea from chronic idiopathic colitis was enzootic. A survey performed in a second colony of rhesus monkeys without a history of chronic diarrhoea determined that 57 % were faecal-culture positive for Helicobacter species. Ten years after the survey, one of the animals from which ‘H. macacae’ had been isolated, a 23-year-old, intact male rhesus monkey (Macaca mulatta), presented with partial inappetence and progressive weight loss. Subsequent evaluation of the monkey revealed anaemia, hypoproteinaemia, hypoalbuminaemia and a palpable abdominal mass. Contrast radiography suggested partial intestinal obstruction. The animal was euthanized and a diagnosis was made of intestinal adenocarcinoma of the ileocaecocolic junction with metastasis to regional lymph nodes and liver. Microaerobic culture of caecal tissue yielded a helicobacter organism identified as ‘H. macacae’ by 16S rRNA gene sequencing – the same species of bacteria isolated 10 years previously. The liver, small intestine and colon were also positive by PCR for Helicobacter species. Intestinal adenocarcinoma is the most common malignancy of aged macaques. Faeces or caecal tissue from five out of five monkeys that remained from the original cohort and that were colonized with ‘H. macacae’ in the initial survey were positive for the organism. The apparent persistence of ‘H. macacae’ in these animals, the isolation of the bacterium from animals with colitis and the recognition of the importance of inflammation in carcinogenesis raise the possibility of an aetiological role in the genesis of intestinal adenocarcinoma in aged rhesus monkeys. PMID:20413623

  10. Severe oxidative stress in an acute inflammatory demyelinating model in the rhesus monkey.

    PubMed

    Dunham, Jordon; van de Vis, Reinofke; Bauer, Jan; Wubben, Jacqueline; van Driel, Nikki; Laman, Jon D; 't Hart, Bert A; Kap, Yolanda S

    2017-01-01

    Oxidative stress is increasingly implicated as a co-factor of tissue injury in inflammatory/demyelinating disorders of the central nervous system (CNS), such as multiple sclerosis (MS). While rodent experimental autoimmune encephalomyelitis (EAE) models diverge from human demyelinating disorders with respect to limited oxidative injury, we observed that in a non-human primate (NHP) model for MS, namely EAE in the common marmoset, key pathological features of the disease were recapitulated, including oxidative tissue injury. Here, we investigated the presence of oxidative injury in another NHP EAE model, i.e. in rhesus macaques, which yields an acute demyelinating disease, which may more closely resemble acute disseminated encephalomyelitis (ADEM) than MS. Rhesus monkey EAE diverges from marmoset EAE by abundant neutrophil recruitment into the CNS and destructive injury to white matter. This difference prompted us to investigate to which extent the oxidative pathway features elicited in MS and marmoset EAE are reflected in the acute rhesus monkey EAE model. The rhesus EAE brain was characterized by widespread demyelination and active lesions containing numerous phagocytic cells and to a lesser extent T cells. We observed induction of the oxidative stress pathway, including injury, with a predilection of p22phox expression in neutrophils and macrophages/microglia. In addition, changes in iron were observed. These results indicate that pathogenic mechanisms in the rhesus EAE model may differ from the marmoset EAE and MS brain due to the neutrophil involvement, but may in the end lead to similar induction of oxidative stress and injury.

  11. Sex differences in rhesus monkey toy preferences parallel those of children

    PubMed Central

    Hassett, Janice M.; Siebert, Erin R.; Wallen, Kim

    2008-01-01

    Socialization processes, parents, or peers encouraging play with gender specific toys are thought to be the primary force shaping sex differences in toy preference. A contrast in view is that toy preferences reflect biologically determined preferences for specific activities facilitated by specific toys. Sex differences in juvenile activities, such as rough and tumble play, peer preferences, and infant interest, share similarities in humans and monkeys. Thus if activity preferences shape toy preferences, male and female monkeys may show toy preferences similar to those seen in boys and girls. We compared the interactions of 34 rhesus monkeys, living within a 135 monkey troop, with human wheeled toys and plush toys. Male monkeys, like boys, showed consistent and strong preferences for wheeled toys, while female monkeys, like girls, showed greater variability in preferences. Thus, the magnitude of preference for wheeled over plush toys differed significantly between males and females. The similarities to human findings demonstrate that such preferences can develop without explicit gendered socialization. We offer the hypothesis that toy preferences reflect hormonally influenced behavioral and cognitive biases which are sculpted by social processes into the sex differences seen in monkeys and humans. PMID:18452921

  12. The kinematic recovery process of rhesus monkeys after spinal cord injury.

    PubMed

    Wei, Rui-Han; Zhao, Can; Rao, Jia-Sheng; Zhao, Wen; Zhou, Xia; Tian, Peng-Yu; Song, Wei; Ji, Run; Zhang, Ai-Feng; Yang, Zhao-Yang; Li, Xiao-Guang

    2018-05-16

    After incomplete spinal cord injury (SCI), neural circuits may be plastically reconstructed to some degree, resulting in extensive functional locomotor recovery. The present study aimed to observe the post-SCI locomotor recovery of rhesus monkey hindlimbs and compare the recovery degrees of different hindlimb parts, thus revealing the recovery process of locomotor function. Four rhesus monkeys were chosen for thoracic hemisection injury. The hindlimb locomotor performance of these animals was recorded before surgery, as well as 6 and 12 weeks post-lesion. Via principal component analysis, the relevant parameters of the limb endpoint, pelvis, hindlimb segments, and joints were processed and analyzed. Twelve weeks after surgery, partial kinematic recovery was observed at the limb endpoint, shank, foot, and knee joints, and the locomotor performance of the ankle joint even recovered to the pre-lesion level; the elevation angle of the thigh and hip joints showed no obvious recovery. Generally, different parts of a monkey hindlimb had different spontaneous recovery processes; specifically, the closer the part was to the distal end, the more extensive was the locomotor function recovery. Therefore, we speculate that locomotor recovery may be attributed to plastic reconstruction of the motor circuits that are mainly composed of corticospinal tract. This would help to further understand the plasticity of motor circuits after spinal cord injury.

  13. RepSox improves viability and regulates gene expression in rhesus monkey-pig interspecies cloned embryos.

    PubMed

    Zhu, Hai-Ying; Jin, Long; Guo, Qing; Luo, Zhao-Bo; Li, Xiao-Chen; Zhang, Yu-Chen; Xing, Xiao-Xu; Xuan, Mei-Fu; Zhang, Guang-Lei; Luo, Qi-Rong; Wang, Jun-Xia; Cui, Cheng-Du; Li, Wen-Xue; Cui, Zheng-Yun; Yin, Xi-Jun; Kang, Jin-Dan

    2017-05-01

    To investigate the effect of the small molecule, RepSox, on the expression of developmentally important genes and the pre-implantation development of rhesus monkey-pig interspecies somatic cell nuclear transfer (iSCNT) embryos. Rhesus monkey cells expressing the monomeric red fluorescent protein 1 which have a normal (42) chromosome complement, were used as donor cells to generate iSCNT embryos. RepSox increased the expression levels of the pluripotency-related genes, Oct4 and Nanog (p < 0.05), but not of Sox2 compared with untreated embryos at the 2-4-cell stage. Expression of the anti-apoptotic gene, Bcl2, and the pro-apoptotic gene Bax was also affected at the 2-4-cell stage. RepSox treatment also increased the immunostaining intensity of Oct4 at the blastocyst stage (p < 0.05). Although the blastocyst developmental rate was higher in the group treated with 25 µM RepSox for 24 h than in the untreated control group (2.4 vs. 1.2%, p > 0.05), this was not significant. RepSox can improve the developmental potential of rhesus monkey-pig iSCNT embryos by regulating the expression of pluripotency-related genes.

  14. Protective efficacy of recombinant BCG Tokyo (Ag85A) in rhesus monkeys (Macaca mulatta) infected intratracheally with H37Rv Mycobacterium tuberculosis.

    PubMed

    Sugawara, I; Sun, L; Mizuno, S; Taniyama, T

    2009-01-01

    We have reported previously that recombinant BCG Tokyo (Ag85A) (rBCG-Ag85A[Tokyo]) shows promise as a tuberculosis vaccine, demonstrating protective efficacy in cynomolgus monkeys. As a next step, rhesus monkeys were utilized because they are also susceptible to Mycobacterium tuberculosis and show a continuous course of infection resembling human tuberculosis. The recombinant BCG vaccine (5x10(5) CFU per monkey) was administered once intradermally into the back skin to three groups of rhesus monkeys, and its protective efficacy was compared for 4months with that of its parental BCG Tokyo strain. Eight week vaccination of the monkeys with rBCG-Ag85A[Tokyo] resulted in a reduction of tubercle bacilli CFU (p<0.01) and lung pathology in animals infected intratracheally with 3000 CFU H37Rv M. tuberculosis. Vaccination prevented an increase in the old tuberculin test after challenge with M. tuberculosis and reaction of M. tuberculosis-derived antigen. Thus, it was shown that even in rhesus monkeys rBCG-Ag85A[Tokyo] induced higher protective efficacy than BCG Tokyo.

  15. Program Review: The Lifetime Effects of Space Radiation in Rhesus Monkeys

    DTIC Science & Technology

    1990-03-01

    6 Endometriosis ........................................................... 6 Hematology and Biochemistry...becomes an important consideration at higher proton energies. The head of the juvenile rhesus monkey could be examined in a CAT scan in order to...brain become important. Calculations based on data from CAT scans, which take into account the variation in size of the human head, should be made to

  16. Quantity Representation in Children and Rhesus Monkeys: Linear Versus Logarithmic Scales

    ERIC Educational Resources Information Center

    Beran, Michael J.; Johnson-Pynn, Julie S.; Ready, Christopher

    2008-01-01

    The performances of 4- and 5-year-olds and rhesus monkeys were compared using a computerized task for quantity assessment. Participants first learned two quantity anchor values and then responded to intermediate values by classifying them as similar to either the large anchor or the small anchor. Of primary interest was an assessment of where the…

  17. Rhesus monkey lens as an in vitro model for studying oxidative stress

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zigler, J.S. Jr.; Lucas, V.A.; Du, X.Y.

    1989-10-01

    Lenses from young rhesus monkeys were incubated in the presence of H{sub 2}O{sub 2} or oxygen radical generating systems to determine their suitability as a model for investigating lenticular oxidative stress. Additionally, direct comparisons were made between the effects found with the monkey lenses and those observed with cultured rat lenses exposed to the same oxidizing systems. As in earlier studies with rat lenses the monkey lenses exhibited impaired ability to actively accumulate from the medium radioactively labelled rubidium and choline following exposure to oxidative stress. Based on the effects of various scavengers of oxygen radicals it appeared that themore » mechanisms responsible for lens damage were the same for both rat and monkey lenses. However, rat lenses were damaged by lower concentrations of oxidants than were monkey lenses. It was concluded that oxidative stress affects both rat and monkey lenses by similar mechanisms but that lenses from monkeys, and probably other primates, are more resistant to these effects because they have better endogenous antioxidant defenses.« less

  18. Quantification of Drug Choice with the Generalized Matching Law in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Koffarnus, Mikhail N.; Woods, James H.

    2008-01-01

    The generalized matching law provides precise descriptions of choice, but has not been used to characterize choice between different doses of drugs or different classes of drugs. The current study examined rhesus monkeys' drug self-administration choices between identical drug doses, different doses, different drugs (cocaine, remifentanil, and…

  19. Performance norms for a rhesus monkey neuropsychological testing battery: acquisition and long-term performance.

    PubMed

    Weed, M R; Taffe, M A; Polis, I; Roberts, A C; Robbins, T W; Koob, G F; Bloom, F E; Gold, L H

    1999-10-25

    A computerized behavioral battery based upon human neuropsychological tests (CANTAB, CeNeS, Cambridge, UK) has been developed to assess cognitive behaviors of rhesus monkeys. Monkeys reliably performed multiple tasks, providing long-term assessment of changes in a number of behaviors for a given animal. The overall goal of the test battery is to characterize changes in cognitive behaviors following central nervous system (CNS) manipulations. The battery addresses memory (delayed non-matching to sample, DNMS; spatial working memory, using a self-ordered spatial search task, SOSS), attention (intra-/extra-dimensional shift, ID/ED), motivation (progressive-ratio, PR), reaction time (RT) and motor coordination (bimanual task). As with human neuropsychological batteries, different tasks are thought to involve different neural substrates, and therefore performance profiles should assess function in particular brain regions. Monkeys were tested in transport cages, and responding on a touch sensitive computer monitor was maintained by food reinforcement. Parametric manipulations of several tasks demonstrated the sensitivity of performance to increases in task difficulty. Furthermore, the factors influencing difficulty for rhesus monkeys were the same as those shown to affect human performance. Data from this study represent performance of a population of healthy normal monkeys that will be used for comparison in subsequent studies of performance following CNS manipulations such as infection with simian immunodeficiency virus (NeuroAIDS) or drug administration.

  20. Two-item same/different discrimination in rhesus monkeys (Macaca mulatta).

    PubMed

    Basile, Benjamin M; Moylan, Emily J; Charles, David P; Murray, Elisabeth A

    2015-11-01

    Almost all nonhuman animals can recognize when one item is the same as another item. It is less clear whether nonhuman animals possess abstract concepts of "same" and "different" that can be divorced from perceptual similarity. Pigeons and monkeys show inconsistent performance, and often surprising difficulty, in laboratory tests of same/different learning that involve only two items. Previous results from tests using multi-item arrays suggest that nonhumans compute sameness along a continuous scale of perceptual variability, which would explain the difficulty of making two-item same/different judgments. Here, we provide evidence that rhesus monkeys can learn a two-item same/different discrimination similar to those on which monkeys and pigeons have previously failed. Monkeys' performance transferred to novel stimuli and was not affected by perceptual variations in stimulus size, rotation, view, or luminance. Success without the use of multi-item arrays, and the lack of effect of perceptual variability, suggests a computation of sameness that is more categorical, and perhaps more abstract, than previously thought.

  1. Intrapericardial denervation: Responses to water immersion in rhesus monkeys

    NASA Technical Reports Server (NTRS)

    McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold

    1995-01-01

    Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings. water immersion; natriuresis; vasopressin; eardiae denervation; monkey

  2. Fetal Iron Deficiency and Genotype Influence Emotionality in Infant Rhesus Monkeys123

    PubMed Central

    Golub, Mari S; Hogrefe, Casey E

    2015-01-01

    Background: Anemia during the third trimester of fetal development affects one-third of the pregnancies in the United States and has been associated with postnatal behavioral outcomes. This study examines how fetal iron deficiency (ID) interacts with the fetal monoamine oxidase A (MAOA) genotype. MAOA metabolizes monoamine neurotransmitters. MAOA polymorphisms in humans affect temperament and modify the influence of early adverse environments on later behavior. Objective: The aim of the study was to advance translation of developmental ID research in animal models by taking into account genetic factors that influence outcomes in human populations. Methods: Male infant rhesus monkeys 3–4 mo old born to mothers fed an ID (10 ppm iron) diet were compared with controls (100 ppm iron). Infant monkeys with high- or low-transcription rate MAOA polymorphisms were equally distributed between diet groups. Behavioral responses to a series of structured experiences were recorded during a 25-h separation of the infants from their mothers. Results: Infant monkeys with low-transcription MAOA polymorphisms more clearly demonstrated the following ID effects suggested in earlier studies: a 4% smaller head circumference, a 39% lower cortisol response to social separation, a 129% longer engagement with novel visual stimuli, and 33% lesser withdrawal in response to a human intruder. The high MAOA genotype ID monkeys demonstrated other ID effects: less withdrawal and emotionality after social separation and lower “fearful” ratings. Conclusion: MAOA × ID interactions support the role of monoamine neurotransmitters in prenatal ID effects in rhesus monkeys and the potential involvement of common human polymorphisms in determining the pattern of neurobehavioral effects produced by inadequate prenatal nutrition. PMID:25733484

  3. Biological Rhythms and Temperature Regulation in Rhesus Monkeys During Spaceflight

    NASA Technical Reports Server (NTRS)

    Fuller, Charles A. (Principal Investigator)

    1996-01-01

    This program examined the influence of microgravity on temperature regulation and circadian timekeeping systems in Rhesus monkeys. Animals flown on the Soviet Biosatellite COSMOS 2229 were exposed to 11 2/3 days of microgravity. The circadian patterns temperature regulation, heart rate and activity were monitored constantly. This experiment has extended previous observations from COSMOS 1514 and 2044, as well as provided insights into the physiological mechanisms that produce these changes.

  4. Long-term reproducibility of Edinger-Westphal stimulated accommodation in rhesus monkeys.

    PubMed

    He, Lin; Wendt, Mark; Glasser, Adrian

    2013-08-01

    If longitudinal studies of accommodation or accommodation restoration procedures are undertaken in rhesus monkeys, the methods used to induce and measure accommodation must remain reproducible over the study period. Stimulation of the Edinger-Westphal (EW) nucleus in anesthetized rhesus monkeys is a valuable method to understand various aspects of accommodation. A prior study showed reproducibility of EW-stimulated accommodation over 14 months after chronic electrode implantation. However, reproducibility over a period longer than this has not been investigated and therefore remains unknown. To address this, accommodation stimulation experiments in four eyes of two rhesus monkeys (13.7 and 13.8 years old) were evaluated over a period of 68 months. Carbachol iontophoresis stimulated accommodation was first measured with a Hartinger coincidence refractometer (HCR) two weeks before electrode implantation to determine maximum accommodative amplitudes. EW stimulus-response curves were initially measured with the HCR one month after electrode implantation and then repeated at least six times for each eye in the following 60 months. At 64 months, carbachol iontophoresis induced accommodation was measured again. At 68 months, EW stimulus-response curves were measured with an HCR and photorefraction every week over four consecutive weeks to evaluate the short-term reproducibility over one month. In the four eyes studied, long-term EW-stimulated accommodation decreased by 7.00 D, 3.33 D, 4.63 D, and 2.03 D, whereas carbachol stimulated accommodation increased by 0.18 D-0.49 D over the same time period. The short-term reproducibility of maximum EW-stimulated accommodation (standard deviations) over a period of four weeks at 68 months after electrode implantation was 0.48 D, 0.79 D, 0.55 D and 0.39 D in the four eyes. Since the long-term decrease in EW-stimulated accommodation is not matched by similar decreases in carbachol iontophoresis stimulated accommodation, the decline

  5. Spaceflight and immune responses of rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1995-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-a (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CD8+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  6. Dissociation of item and source memory in rhesus monkeys.

    PubMed

    Basile, Benjamin M; Hampton, Robert R

    2017-09-01

    Source memory, or memory for the context in which a memory was formed, is a defining characteristic of human episodic memory and source memory errors are a debilitating symptom of memory dysfunction. Evidence for source memory in nonhuman primates is sparse despite considerable evidence for other types of sophisticated memory and the practical need for good models of episodic memory in nonhuman primates. A previous study showed that rhesus monkeys confused the identity of a monkey they saw with a monkey they heard, but only after an extended memory delay. This suggests that they initially remembered the source - visual or auditory - of the information but forgot the source as time passed. Here, we present a monkey model of source memory that is based on this previous study. In each trial, monkeys studied two images, one that they simply viewed and touched and the other that they classified as a bird, fish, flower, or person. In a subsequent memory test, they were required to select the image from one source but avoid the other. With training, monkeys learned to suppress responding to images from the to-be-avoided source. After longer memory intervals, monkeys continued to show reliable item memory, discriminating studied images from distractors, but made many source memory errors. Monkeys discriminated source based on study method, not study order, providing preliminary evidence that our manipulation of retention interval caused errors due to source forgetting instead of source confusion. Finally, some monkeys learned to select remembered images from either source on cue, showing that they did indeed remember both items and both sources. This paradigm potentially provides a new model to study a critical aspect of episodic memory in nonhuman primates. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Intranasal Opioid Administration in Rhesus Monkeys: PET Imaging and Antinociception.

    PubMed

    Saccone, Phillip A; Lindsey, Angela M; Koeppe, Robert A; Zelenock, Kathy A; Shao, Xia; Sherman, Phillip; Quesada, Carole A; Woods, James H; Scott, Peter J H

    2016-11-01

    The goal of this study was to evaluate the effects of intranasally administered opioids in rhesus monkeys using the tail-withdrawal assay, and to correlate these effects with measures of receptor occupancy using positron emission tomography (PET) imaging. Initial experiments characterized the antinociceptive effects of intranasal (IN) fentanyl and buprenorphine relative to intramuscular (IM) injection. Fentanyl (0.010-0.032 mg/kg) and buprenorphine (0.1-1.0 mg/kg) produced dose-dependent increases in tail-withdrawal latency that did not differ between routes of delivery. The second experiment compared the ability of IN and intravenous (IV) naloxone (NLX) to block the antinociceptive effects IV fentanyl, and to measure receptor occupancy at equipotent doses of NLX using PET imaging. IN and IV NLX (0.0032-0.032 mg/kg) produced dose-dependent decreases in fentanyl-induced antinociception. Again, there was no difference observed in overall potency between routes. PET imaging showed that IV and IN NLX produced similar decreases in receptor occupancy as measured by [ 11 C]carfentanil blocking, although there was a trend for IV NLX to produce marginally greater occupancy changes. This study validated the first procedures to evaluate the IN effects of opioids in rhesus monkeys. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  8. Effect of radiation and age on immunoglobulin levels in rhesus monkeys (Macaca mulatta)

    NASA Technical Reports Server (NTRS)

    Stone, W. H.; Saphire, D. G.; Hackleman, S. M.; Braun, A. M.; Pennington, P.; Scheffler, J.; Wigle, J. C.; Cox, A. B.

    1994-01-01

    We report the results of a study on the immunoglobulin levels of rhesus monkeys (Macaca mulatta) in a colony consisting of the survivors of monkeys that received a single whole-body exposure to protons, electrons or X rays between 1964 and 1969. This colony has been maintained to assess the long-term effects of ionizing radiation on astronauts and high-flying pilots. Of the original 358 monkeys that were retained for lifetime studies, 129 (97 irradiated and 32 controls) were available for our study. We found no significant difference between the irradiated and control monkeys in mean levels of IgA, IgG and IgM, irrespective of the radiation treatment. The availability of these aged monkeys provided a unique opportunity to compare their immunoglobulin levels to those of other monkeys of various ages, and thus assess the effect of age on immunoglobulin levels. We found that only the IgA levels increase with age.

  9. Genes involved in leukotriene synthesis pathway are dynamically regulated during lung development in Rhesus monkeys.

    PubMed

    Xia, Wanmin; Xie, Liang; Cao, Bangrong; Cheng, Shujun; Wan, Huajing; Liu, Hanmin

    2017-07-01

    Leukotrienes play critical roles in many inflammatory lung diseases and several antagonists of their receptors have been used in the clinical settings. However, the physiological functions of leukotrienes in lung development are still unclear. The expression levels of 34 genes involved in leukotriene synthesis and function pathway in the lungs of Rhesus monkey during different developmental time points were determined on a MiSeq platform and analyzed by the reads per kilobase of transcript per million mapped reads (RPKM) method. The results showed that the expression levels of PLA2G1B, PLA2G10, PLA2G2D, ALOX5, and ALOX5AP increased dramatically in the lung of Rhesus monkey, reflecting the changes in the pulmonary environment after delivery. Additionally, the different expression patterns between molecules related to LTB4 and LTC4 synthesis suggested distinct roles of LTB4 and LTC4 in lung development. Finally, the constant expression of CysLT1 during the development process provided new information to the pharmaceutical basis of the use of leukotriene receptor antagonists in the clinical setting. The expression levels of several key genes involved in leukotriene synthesis changed dramatically during lung development in Rhesus monkeys, suggesting the potential roles of leukotrienes in lung development in this animal model. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Disruptions in follicle cell functions in the ovaries of rhesus monkeys during summer

    PubMed Central

    VandeVoort, Catherine A.; Mtango, Namdori R.; Midic, Uros

    2015-01-01

    Oocytes isolated from female rhesus monkeys following standard ovarian stimulation protocols during the summer months displayed a reduced capacity to mature compared with stimulation during the normal breeding season. Because the gene expression profiles of oocyte-associated cumulus cells and mural granulosa cells (CCs and GCs) are indicative of altered oocyte quality and can provide insight into intrafollicular processes that may be disrupted during oogenesis, we performed array-based transcriptome comparisons of CCs and GCs from summer and normal breeding season stimulation cycles. Summer CCs and GCs both display deficiencies in expression of mRNAs related to cell proliferation, angiogenesis, and endocrine signaling, as well as reduced expression of glycogen phosphorylase. Additionally, CCs display deficiencies in expression of mRNAs related to stress response. These results provide the first insight into the specific molecular pathways and processes that are disrupted in the follicles of rhesus macaque females during the summer season. Some of the changes seen in summer GCs and CCs have been reported in humans and in other model mammalian species. This suggests that the seasonal effects seen in the rhesus monkey may help us to understand better the mechanisms that contribute to reduced oocyte quality and fertility in humans. PMID:25586978

  11. Empty Sets as Part of the Numerical Continuum: Conceptual Precursors to the Zero Concept in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Merritt, Dustin J.; Rugani, Rosa; Brannon, Elizabeth M.

    2009-01-01

    The goal of the current research was to explore whether monkeys possess conceptual precursors necessary for understanding zero. We trained rhesus monkeys on a nonsymbolic numerical matching-to-sample task, and on a numerical ordering task. We then introduced nondifferentially reinforced trials that contained empty sets to determine whether monkeys…

  12. Pharmacokinetics of doxylamine, a component of Bendectin, in the rhesus monkey.

    PubMed

    Slikker, W; Holder, C L; Lipe, G W; Bailey, J R; Young, J F

    1989-01-01

    The elimination of doxylamine and metabolites was determined after iv administration of [14C]doxylamine succinate at 0.7 and 13.3 mg/kg to the adult female rhesus monkey. Although the total recovery of radioactivity was the same for the low- and high-dose studies (90.2%), the rate of plasma elimination of doxylamine and its demethylated metabolite (desmethyldoxylamine) was slower for the high dose group. The 24 hr urinary excretion of doxylamine metabolites, desmethyl- and didesmethyldoxylamine, was significantly increased and the polar doxylamine metabolites were significantly decreased as the iv doxylamine succinate dose was increased. The plasma elimination of gas chromatograph (GC)-detected doxylamine was determined after oral administration of Bendectin (doxylamine succinate and pyridoxine hydrochloride) at 7, 13.3, and 27 mg/kg to adult female rhesus monkeys. As the dose increased, the clearance of doxylamine decreased. A statistically evaluated fit of the oral data to a single-compartment, parallel first-order elimination model and a single-compartment, parallel first- and second-order (Michaelis-Menten) elimination model indicated that the more complex model containing the second-order process was most consistent with the observed elimination data.

  13. Visual recognition memory and auditory brainstem response in infant rhesus monkeys exposed perinatally to environmental tobacco smoke.

    PubMed

    Golub, Mari S; Slotkin, Theodore A; Tarantal, Alice F; Pinkerton, Kent E

    2007-06-02

    The impact of perinatal exposure to environmental tobacco smoke (ETS) on cognitive development is controversial. We exposed rhesus monkeys to ETS or filtered air (5 animals per group) beginning in utero on day 50 of pregnancy and continuing throughout postnatal testing. In infancy, we evaluated both groups for visual recognition memory and auditory function (auditory brainstem response). The ETS group showed significantly less novelty preference in the visual recognition task whereas no effects on auditory function were detected. These preliminary results support the view that perinatal ETS exposure has adverse effects on cognitive function and indicate further that rhesus monkeys may provide a valuable nonhuman primate model for investigating this link.

  14. The rhesus monkey (Macaca mulatta) as a flight candidate

    NASA Technical Reports Server (NTRS)

    Debourne, M. N. G.; Bourne, G. H.; Mcclure, H. M.

    1977-01-01

    The intelligence and ruggedness of rhesus monkeys, as well as the abundance of normative data on their anatomy, physiology, and biochemistry, and the availability of captive bred animals qualify them for selection as candidates for orbital flight and weightlessness studies. Baseline data discussed include: physical characteristics, auditory thresholds, visual accuity, blood, serological taxomony, immunogenetics, cytogenics, circadian rhythms, respiration, cardiovascular values, corticosteroid response to charr restraint, microscopy of tissues, pathology, nutrition, and learning skills. Results from various tests used to establish the baseline data are presented in tables.

  15. Intrapericardial Denervation: Responses to Water Immersion in Rhesus Monkeys

    NASA Technical Reports Server (NTRS)

    McKeever, Kenneth H.; Keil, Lanny C.; Sandler, Harold

    1995-01-01

    Eleven anesthetized rhesus monkeys were used to study cardiovascular, renal, and endocrine alterations associated with 120 min of head-out water immersion. Five animals underwent complete intrapericardial denervation using the Randall technique, while the remaining six monkeys served as intact controls. Each animal was chronically instrumented with an electromagnetic flow probe on the ascending aorta, a strain gauge pressure transducer implanted in the apex of the left ventricle (LV), and electrocardiogram leads anchored to the chest wall and LV. During immersion, LV end-diastolic pressure, urine flow, glomerular filtration rate, sodium excretion, and circulating atrial natriuretic peptide (ANP) each increased (P less than 0.05) for intact and denervated monkeys. There were no alterations in free water clearance in either group during immersion, yet fractional excretion of free water increased (P less than 0.05) in the intact monkeys. Plasma renin activity (PRA) decreased (P less than 0.05) during immersion in intact monkeys but not the denervated animals. Plasma vasopressin (PVP) concentration decreased (P less than 0.05) during the first 30 min of immersion in both groups but was not distinguishable from control by 60 min of immersion in denervated monkeys. These data demonstrate that complete cardiac denervation does not block the rise in plasma ANP or prevent the natriuresis associated with head-out water immersion. The suppression of PVP during the first minutes of immersion after complete cardiac denervation suggests that extracardiac sensing mechanisms associated with the induced fluid shifts may be responsible for the findings.

  16. Event-based proactive interference in rhesus monkeys.

    PubMed

    Devkar, Deepna T; Wright, Anthony A

    2016-10-01

    Three rhesus monkeys (Macaca mulatta) were tested in a same/different memory task for proactive interference (PI) from prior trials. PI occurs when a previous sample stimulus appears as a test stimulus on a later trial, does not match the current sample stimulus, and the wrong response "same" is made. Trial-unique pictures (scenes, objects, animals, etc.) were used on most trials, except on trials where the test stimulus matched potentially interfering sample stimulus from a prior trial (1, 2, 4, 8, or 16 trials prior). Greater interference occurred when fewer trials separated interference and test. PI functions showed a continuum of interference. Delays between sample and test stimuli and intertrial intervals were manipulated to test how PI might vary as a function of elapsed time. Contrary to a similar study with pigeons, these time manipulations had no discernable effect on the monkey's PI, as shown by compete overlap of PI functions with no statistical differences or interactions. These results suggested that interference was strictly based upon the number of intervening events (trials with other pictures) without regard to elapsed time. The monkeys' apparent event-based interference was further supported by retesting with a novel set of 1,024 pictures. PI from novel pictures 1 or 2 trials prior was greater than from familiar pictures, a familiar set of 1,024 pictures. Moreover, when potentially interfering novel stimuli were 16 trials prior, performance accuracy was actually greater than accuracy on baseline trials (no interference), suggesting that remembering stimuli from 16 trials prior was a cue that this stimulus was not the sample stimulus on the current trial-a somewhat surprising conclusion particularly given monkeys.

  17. Evidence for kind representations in the absence of language: experiments with rhesus monkeys (Macaca mulatta).

    PubMed

    Phillips, Webb; Santos, Laurie R

    2007-03-01

    How do we come to recognize and represent different kinds of objects in the world? Some developmental psychologists have hypothesized that learning language plays a crucial role in this capacity. If this hypothesis were correct, then non-linguistic animals should lack the capacity to represent objects as kinds. Previous research with rhesus monkeys (Macaca mulatta) has shown that this species can successfully individuate different kinds of objects - monkeys who saw one kind of object hidden inside a box searched longer after finding a different kind of object. However, in these studies and the infant studies on which they were based, the objects to be individuated differed both in kind and in properties. Thus, subjects in these experiments may not be representing the kinds of objects per se, but instead only their immediate perceptual properties. Here, we show that rhesus monkeys successfully individuate different kinds of objects even when their perceptual properties are held constant. Although these data provide the best evidence to date that language is not necessary to represent kinds, we discuss our findings in terms of possible associative hypotheses as well.

  18. Production of rhesus monkey cloned embryos expressing monomeric red fluorescent protein by interspecies somatic cell nuclear transfer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhu, Hai-Ying; Kang, Jin-Dan; Li, Suo

    2014-02-21

    Highlights: • Rhesus monkey cells were electroporated with a plasmid containing mRFP1, and an mRFP1-expressing cell line was generated. • For the first time, mRFP1-expressing rhesus monkey cells were used as donor cells for iSCNT. • The effect of VPA on the development of embryos cloned using iSCNT was determined. - Abstract: Interspecies somatic cell nuclear transfer (iSCNT) is a promising method to clone endangered animals from which oocytes are difficult to obtain. Monomeric red fluorescent protein 1 (mRFP1) is an excellent selection marker for transgenically modified cloned embryos during somatic cell nuclear transfer (SCNT). In this study, mRFP-expressing rhesusmore » monkey cells or porcine cells were transferred into enucleated porcine oocytes to generate iSCNT and SCNT embryos, respectively. The development of these embryos was studied in vitro. The percentage of embryos that underwent cleavage did not significantly differ between iSCNT and SCNT embryos (P > 0.05; 71.53% vs. 80.30%). However, significantly fewer iSCNT embryos than SCNT embryos reached the blastocyst stage (2.04% vs. 10.19%, P < 0.05). Valproic acid was used in an attempt to increase the percentage of iSCNT embryos that developed to the blastocyst stage. However, the percentages of embryos that underwent cleavage and reached the blastocyst stage were similar between untreated iSCNT embryos and iSCNT embryos treated with 2 mM valproic acid for 24 h (72.12% vs. 70.83% and 2.67% vs. 2.35%, respectively). These data suggest that porcine-rhesus monkey interspecies embryos can be generated that efficiently express mRFP1. However, a significantly lower proportion of iSCNT embryos than SCNT embryos reach the blastocyst stage. Valproic acid does not increase the percentage of porcine-rhesus monkey iSCNT embryos that reach the blastocyst stage. The mechanisms underling nuclear reprogramming and epigenetic modifications in iSCNT need to be investigated further.« less

  19. Do you see what I see? A comparative investigation of the Delboeuf illusion in humans (Homo sapiens), rhesus monkeys (Macaca mulatta), and capuchin monkeys (Cebus apella).

    PubMed

    Parrish, Audrey E; Brosnan, Sarah F; Beran, Michael J

    2015-10-01

    Studying visual illusions is critical to understanding typical visual perception. We investigated whether rhesus monkeys (Macaca mulatta) and capuchin monkeys (Cebus apella) perceived the Delboeuf illusion in a similar manner as human adults (Homo sapiens). To test this, in Experiment 1, we presented monkeys and humans with a relative discrimination task that required subjects to choose the larger of 2 central dots that were sometimes encircled by concentric rings. As predicted, humans demonstrated evidence of the Delboeuf illusion, overestimating central dots when small rings surrounded them and underestimating the size of central dots when large rings surrounded them. However, monkeys did not show evidence of the illusion. To rule out an alternate explanation, in Experiment 2, we presented all species with an absolute classification task that required them to classify a central dot as "small" or "large." We presented a range of ring sizes to determine whether the Delboeuf illusion would occur for any dot-to-ring ratios. Here, we found evidence of the Delboeuf illusion in all 3 species. Humans and monkeys underestimated central dot size to a progressively greater degree with progressively larger rings. The Delboeuf illusion now has been extended to include capuchin monkeys and rhesus monkeys, and through such comparative investigations we can better evaluate hypotheses regarding illusion perception among nonhuman animals. (c) 2015 APA, all rights reserved).

  20. Nutritional manipulation of primate retinas, I: effects of lutein or zeaxanthin supplements on serum and macular pigment in xanthophyll-free rhesus monkeys.

    PubMed

    Neuringer, Martha; Sandstrom, Marita M; Johnson, Elizabeth J; Snodderly, D Max

    2004-09-01

    The xanthophylls lutein (L) and zeaxanthin (Z) are the primary components of macular pigment (MP) and may protect the macula from age-related degeneration (AMD). In this study, L or Z was fed to rhesus monkeys reared on xanthophyll-free diets to follow the accumulation of serum carotenoids and MP over time. Eighteen rhesus monkeys were fed xanthophyll-free semipurified diets from birth until 7 to 16 years. The diets of six were then supplemented with pure L and six with pure Z at 3.9 micromol/kg per day (2.2 mg/kg per day) for 24 to 56 weeks. At baseline and 4- to 12-week intervals during supplementation, serum carotenoids were measured by HPLC, and MP density was estimated by two-wavelength reflectometry. Serum carotenoids and MP were also measured in monkeys fed a stock diet. Monkeys fed xanthophyll-free diets had no L or Z in serum and no detectable MP. During supplementation, serum L or Z increased rapidly over the first 4 weeks and from 16 weeks onward maintained similar levels, both several times higher than in stock-diet-fed monkeys. The central peak of MP optical density increased to a relatively steady level by 24 to 32 weeks in both L- and Z-fed groups. Rhesus monkeys fed a stock diet had lower blood concentrations of L than those found in humans and other nonhuman primates. Rhesus monkeys respond to either dietary L or Z supplementation with increases in serum xanthophylls and MP, even after life-long xanthophyll deficiency. These animals provide a potential model to study mechanisms of protection from AMD. Copyright Association for Research in Vision and Ophthalmology

  1. Rhesus Monkey - Miss Sam - Fiberglass Couch - Little Joe (LJ)-1B Flight - Prep

    NASA Image and Video Library

    1959-12-04

    B59-00828 (21 Jan. 1959) --- The test subject, a rhesus monkey named Miss Sam, is seen encased in a model of the Mercury fiberglass contour couch. She is being placed in a container for the Little Joe 1B suborbital test flight of the Mercury Capsule. Photo credit: NASA

  2. Face Pareidolia in the Rhesus Monkey.

    PubMed

    Taubert, Jessica; Wardle, Susan G; Flessert, Molly; Leopold, David A; Ungerleider, Leslie G

    2017-08-21

    Face perception in humans and nonhuman primates is rapid and accurate [1-4]. In the human brain, a network of visual-processing regions is specialized for faces [5-7]. Although face processing is a priority of the primate visual system, face detection is not infallible. Face pareidolia is the compelling illusion of perceiving facial features on inanimate objects, such as the illusory face on the surface of the moon. Although face pareidolia is commonly experienced by humans, its presence in other species is unknown. Here we provide evidence for face pareidolia in a species known to possess a complex face-processing system [8-10]: the rhesus monkey (Macaca mulatta). In a visual preference task [11, 12], monkeys looked longer at photographs of objects that elicited face pareidolia in human observers than at photographs of similar objects that did not elicit illusory faces. Examination of eye movements revealed that monkeys fixated the illusory internal facial features in a pattern consistent with how they view photographs of faces [13]. Although the specialized response to faces observed in humans [1, 3, 5-7, 14] is often argued to be continuous across primates [4, 15], it was previously unclear whether face pareidolia arose from a uniquely human capacity. For example, pareidolia could be a product of the human aptitude for perceptual abstraction or result from frequent exposure to cartoons and illustrations that anthropomorphize inanimate objects. Instead, our results indicate that the perception of illusory facial features on inanimate objects is driven by a broadly tuned face-detection mechanism that we share with other species. Published by Elsevier Ltd.

  3. Caloric restriction improves health and survival of rhesus monkeys.

    PubMed

    Mattison, Julie A; Colman, Ricki J; Beasley, T Mark; Allison, David B; Kemnitz, Joseph W; Roth, George S; Ingram, Donald K; Weindruch, Richard; de Cabo, Rafael; Anderson, Rozalyn M

    2017-01-17

    Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health.

  4. Wave aberrations in rhesus monkeys with vision-induced ametropias

    PubMed Central

    Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Huang, Juan; Roorda, Austin; Smith, Earl L.

    2007-01-01

    The purpose of this study was to investigate the relationship between refractive errors and high-order aberrations in infant rhesus monkeys. Specifically, we compared the monochromatic wave aberrations measured with a Shack-Hartman wavefront sensor between normal monkeys and monkeys with vision-induced refractive errors. Shortly after birth, both normal monkeys and treated monkeys reared with optically induced defocus or form deprivation showed a decrease in the magnitude of high-order aberrations with age. However, the decrease in aberrations was typically smaller in the treated animals. Thus, at the end of the lens-rearing period, higher than normal amounts of aberrations were observed in treated eyes, both hyperopic and myopic eyes and treated eyes that developed astigmatism, but not spherical ametropias. The total RMS wavefront error increased with the degree of spherical refractive error, but was not correlated with the degree of astigmatism. Both myopic and hyperopic treated eyes showed elevated amounts of coma and trefoil and the degree of trefoil increased with the degree of spherical ametropia. Myopic eyes also exhibited a much higher prevalence of positive spherical aberration than normal or treated hyperopic eyes. Following the onset of unrestricted vision, the amount of high-order aberrations decreased in the treated monkeys that also recovered from the experimentally induced refractive errors. Our results demonstrate that high-order aberrations are influenced by visual experience in young primates and that the increase in high-order aberrations in our treated monkeys appears to be an optical byproduct of the vision-induced alterations in ocular growth that underlie changes in refractive error. The results from our study suggest that the higher amounts of wave aberrations observed in ametropic humans are likely to be a consequence, rather than a cause, of abnormal refractive development. PMID:17825347

  5. Personality Structure in Brown Capuchin Monkeys: Comparisons with Chimpanzees, Orangutans, and Rhesus Macaques

    PubMed Central

    Morton, F. Blake; Lee, Phyllis C.; Buchanan-Smith, Hannah M.; Brosnan, Sarah F.; Thierry, Bernard; Paukner, Annika; de Waal, Frans B. M.; Widness, Jane; Essler, Jennifer L.; Weiss, Alexander

    2013-01-01

    Species comparisons of personality structure (i.e. how many personality dimensions and the characteristics of those dimensions) can facilitate questions about the adaptive function of personality in nonhuman primates. Here we investigate personality structure in the brown capuchin monkey (Sapajus apella), a New World primate species, and compare this structure to those of chimpanzees (Pan troglodytes), orangutans (Pongo spp.), and rhesus macaques (Macaca mulatta). Brown capuchins evolved behavioral and cognitive traits that are qualitatively similar to those of great apes, and individual differences in behavior and cognition are closely associated with differences in personality. Thus, we hypothesized that brown capuchin personality structure would overlap more with great apes than with rhesus macaques. We obtained personality ratings from seven sites on 127 brown capuchin monkeys. Principal-components analysis identified five personality dimensions (Assertiveness, Openness, Neuroticism, Sociability, and Attentiveness), which were reliable across raters and, in a subset of subjects, significantly correlated with relevant behaviors up to a year later. Comparisons between species revealed that brown capuchins and great apes overlapped in personality structure, particularly chimpanzees in the case of Neuroticism. However, in some respects (i.e. capuchin Sociability and Openness) the similarities between capuchins and great apes were not significantly greater than those between capuchins and rhesus macaques. We discuss the relevance of our results to brown capuchin behavior, and the evolution of personality structure in primates. PMID:23668695

  6. Competitive control of cognition in rhesus monkeys.

    PubMed

    Kowaguchi, Mayuka; Patel, Nirali P; Bunnell, Megan E; Kralik, Jerald D

    2016-12-01

    The brain has evolved different approaches to solve problems, but the mechanisms that determine which approach to take remain unclear. One possibility is that control progresses from simpler processes, such as associative learning, to more complex ones, such as relational reasoning, when the simpler ones prove inadequate. Alternatively, control could be based on competition between the processes. To test between these possibilities, we posed the support problem to rhesus monkeys using a tool-use paradigm, in which subjects could pull an object (the tool) toward themselves to obtain an otherwise out-of-reach goal item. We initially provided one problem exemplar as a choice: for the correct option, a food item placed on the support tool; for the incorrect option, the food item placed off the tool. Perceptual cues were also correlated with outcome: e.g., red, triangular tool correct, blue, rectangular tool incorrect. Although the monkeys simply needed to touch the tool to register a response, they immediately pulled it, reflecting a relational reasoning process between themselves and another object (R self-other ), rather than an associative one between the arbitrary touch response and reward (A resp-reward ). Probe testing then showed that all four monkeys used a conjunction of perceptual features to select the correct option, reflecting an associative process between stimuli and reward (A stim-reward ). We then added a second problem exemplar and subsequent testing revealed that the monkeys switched to using the on/off relationship, reflecting a relational reasoning process between two objects (R other-other ). Because behavior appeared to reflect R self-other rather than A resp-reward , and A stim-reward prior to R other-other , our results suggest that cognitive processes are selected via competitive control dynamics. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Fetal Neuropathology in Zika Virus-Infected Pregnant Female Rhesus Monkeys.

    PubMed

    Martinot, Amanda J; Abbink, Peter; Afacan, Onur; Prohl, Anna K; Bronson, Roderick; Hecht, Jonathan L; Borducchi, Erica N; Larocca, Rafael A; Peterson, Rebecca L; Rinaldi, William; Ferguson, Melissa; Didier, Peter J; Weiss, Deborah; Lewis, Mark G; De La Barrera, Rafael A; Yang, Edward; Warfield, Simon K; Barouch, Dan H

    2018-05-17

    The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. Movement Limitation and Immune Responses of Rhesus Monkeys

    NASA Technical Reports Server (NTRS)

    Sonnenfeld, Gerald; Morton, Darla S.; Swiggett, Jeanene P.; Hakenewerth, Anne M.; Fowler, Nina A.

    1993-01-01

    The effects of restraint on immunological parameters was determined in an 18 day ARRT (adult rhesus restraint test). The monkeys were restrained for 18 days in the experimental station for the orbiting primate (ESOP), the chair of choice for Space Shuttle experiments. Several immunological parameters were determined using peripheral blood, bone marrow, and lymph node specimens from the monkeys. The parameters included: response of bone marrow cells to GM-CSF (granulocyte-macrophage colony stimulating factor), leukocyte subset distribution, and production of IFN-alpha (interferon-alpha) and IFN-gamma (interferon-gamma). The only parameter changed after 18 days of restraint was the percentage of CDB+ T cells. No other immunological parameters showed changes due to restraint. Handling and changes in housing prior to the restraint period did apparently result in some restraint-independent immunological changes. Handling must be kept to a minimum and the animals allowed time to recover prior to flight. All experiments must be carefully controlled. Restraint does not appear to be a major issue regarding the effects of space flight on immune responses.

  9. Ten-year oral toxicity study with Norlestrin in rhesus monkeys.

    PubMed

    Fitzgerald, J; de la Iglesia, F; Goldenthal, E I

    1982-12-01

    The long term effects of the oral contraceptive, Norlestrin, were evaluated in sexually mature female rhesus (Macaca mulatta) monkeys over a 10 year period. Norlestrin, a combination of norethindrone acetate and ethinylestradiol (50:1) was given orally on a continuous cyclic regimen of 21 d of dosing followed by 7 d without treatment. Groups of 16 monkeys each received the drug at dose levels of 0.05, 0.51, and 2.55 mg/kg representing multiples of 1, 10, and 50 times the human dose, respectively. A comparable group of 16 animals remained untreated and served as controls. Selected clinical and laboratory parameters were monitored throughout the study and all animals were necropsied and evaluated for gross and histopathologic changes. All dose levels were well tolerated and survival was not affected. There were no consistent treatment-related alterations in coagulation or other clinical laboratory parameters. Ophthalmologically, macular pigmentary anomalies were observed in all groups. Treatment-associated pathologic findings, representing exaggerated pharmacological responses with superimposed senile changes, including ovarian and uterine atrophy and dilatation of acini and ducts in the mammary gland. Periodic vaginal cytologic examination and mammary gland palpation did not demonstrate drug related changes. A small number of neoplasms was seen in all groups and a granulosa cell carcinoma of the ovary occurred in a control animal. The benign tumors consisted of three cutaneous papillomas: one in a low dose and one in a high dose animal, a uterine leiomyoma in one high dose animal, and a pancreatic duct adenoma in one low dose animal. The results of this study indicate that Norlestrin had no significant toxic manifestations or tumorigenic potential when administered on a cyclic regimen to female rhesus monkeys at levels up to 50 times the human dose for ten yr.

  10. Amygdala lesions in rhesus monkeys fail to disrupt object choices based on internal context.

    PubMed

    Rhodes, Sarah E V; Charles, David P; Howland, Emily J; Murray, Elisabeth A

    2012-04-01

    We assessed the involvement of the amygdala in a task in which object choices were guided by internal context. Rhesus monkeys were trained on a biconditional discrimination whereby objects associated with food (but not water) were baited when the monkey was hungry, and objects associated with water (but not food) were baited when the monkey was thirsty. To solve this task, monkeys were required to choose objects yielding the reward congruent with their internal motivational state. Lesions of the amygdala did not disrupt learning or performance of this task. We conclude that the involvement of the amygdala in selective-satiation tasks, which depends in part on a change in internal context, is not due to the amygdala playing a general role in representing, or using, internal context. (c) 2012 APA, all rights reserved

  11. Amygdala lesions in rhesus monkeys fail to disrupt object choices based on internal context

    PubMed Central

    Rhodes, Sarah E. V.; Charles, David P.; Howland, Emily J.; Murray, Elisabeth A.

    2012-01-01

    We assessed the involvement of the amygdala in a task in which object choices were guided by internal context. Rhesus monkeys were trained on a biconditional discrimination whereby objects associated with food (but not water) were baited when the monkey was hungry, and objects associated with water (but not food) were baited when the monkey was thirsty. To solve this task monkeys were required to choose objects yielding the reward congruent with their internal motivational state. Lesions of the amygdala did not disrupt learning or performance of this task. We conclude that the involvement of the amygdala in selective-satiation tasks, which depends in part on a change in internal context, is not due to the amygdala playing a general role in representing, or using, internal context. PMID:22352788

  12. Social and nonsocial behaviours of sex- and age-matched enclosed and free-ranging rhesus monkeys (Macaca mulatta).

    PubMed

    Baulu, J; Redmond, D E

    1980-01-01

    The behavioural profiles (time budgeting of social and nonsocial activities) and the frequencies of major social interactions of corral-enclosed rhesus monkeys were compared with sex- and age-matched free-ranging rhesus monkeys on La Cueva Island, Puerto Rico. All animals (n = 32) were provisioned ad libitum at specific feeder sites. The occurrence of 14 behaviours around feeders was compared with their occurrence away from the feeders by noting the location of each monkey relative to the feeder at the time of observation. An analysis of variance between free-ranging versus corral-enclosed groups and within groups by location (around or away from the feeder) revealed significant differences in several behavioural categories, including foraging, lookout, inactive, dominant, submissive, allogrooming, social contact, social initiative, active, and passive behaviours. When the effect of limited food distribution sites was analyzed by comparing data recorded away from the feeding sites, there were remarkably few differences between the groups.

  13. Sterile Protection against Plasmodium knowlesi in Rhesus Monkeys from a Malaria Vaccine: Comparison of Heterologous Prime Boost Strategies

    PubMed Central

    Jiang, George; Shi, Meng; Conteh, Solomon; Richie, Nancy; Banania, Glenna; Geneshan, Harini; Valencia, Anais; Singh, Priti; Aguiar, Joao; Limbach, Keith; Kamrud, Kurt I.; Rayner, Jonathan; Smith, Jonathan; Bruder, Joseph T.; King, C. Richter; Tsuboi, Takafumi; Takeo, Satoru; Endo, Yaeta; Doolan, Denise L.; Richie, Thomas L.; Weiss, Walter R.

    2009-01-01

    Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost. PMID:19668343

  14. Similarity of Bisphenol A Pharmacokinetics in Rhesus Monkeys and Mice: Relevance for Human Exposure

    PubMed Central

    Taylor, Julia A.; vom Saal, Frederick S.; Welshons, Wade V.; Drury, Bertram; Rottinghaus, George; Hunt, Patricia A.; Toutain, Pierre-Louis; Laffont, Céline M.; VandeVoort, Catherine A.

    2011-01-01

    Objective Daily adult human exposure to bisphenol A (BPA) has been estimated at < 1 μg/kg, with virtually complete first-pass conjugation in the liver in primates but not in mice. We measured unconjugated and conjugated BPA levels in serum from adult female rhesus monkeys and adult female mice after oral administration of BPA and compared findings in mice and monkeys with prior published data in women. Methods Eleven adult female rhesus macaques were fed 400 μg/kg deuterated BPA (dBPA) daily for 7 days. Levels of serum dBPA were analyzed by isotope-dilution liquid chromatography–mass spectrometry (0.2 ng/mL limit of quantitation) over 24 hr on day 1 and on day 7. The same dose of BPA was fed to adult female CD-1 mice; other female mice were administered 3H-BPA at doses ranging from 2 to 100,000 μg/kg. Results In monkeys, the maximum unconjugated serum dBPA concentration of 4 ng/mL was reached 1 hr after feeding and declined to low levels by 24 hr, with no significant bioaccumulation after seven daily doses. Mice and monkeys cleared unconjugated serum BPA at virtually identical rates. We observed a linear (proportional) relationship between administered dose and serum BPA in mice. Conclusions BPA pharmacokinetics in women, female monkeys, and mice is very similar. By comparison with approximately 2 ng/mL unconjugated serum BPA reported in multiple human studies, the average 24-hr unconjugated serum BPA concentration of 0.5 ng/mL in both monkeys and mice after a 400 μg/kg oral dose suggests that total daily human exposure is via multiple routes and is much higher than previously assumed. PMID:20855240

  15. Two processes support visual recognition memory in rhesus monkeys.

    PubMed

    Guderian, Sebastian; Brigham, Danielle; Mishkin, Mortimer

    2011-11-29

    A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans.

  16. Caloric restriction improves health and survival of rhesus monkeys

    PubMed Central

    Mattison, Julie A.; Colman, Ricki J.; Beasley, T. Mark; Allison, David B.; Kemnitz, Joseph W.; Roth, George S.; Ingram, Donald K.; Weindruch, Richard; de Cabo, Rafael; Anderson, Rozalyn M.

    2017-01-01

    Caloric restriction (CR) without malnutrition extends lifespan and delays the onset of age-related disorders in most species but its impact in nonhuman primates has been controversial. In the late 1980s two parallel studies were initiated to determine the effect of CR in rhesus monkeys. The University of Wisconsin study reported a significant positive impact of CR on survival, but the National Institute on Aging study detected no significant survival effect. Here we present a direct comparison of longitudinal data from both studies including survival, bodyweight, food intake, fasting glucose levels and age-related morbidity. We describe differences in study design that could contribute to differences in outcomes, and we report species specificity in the impact of CR in terms of optimal onset and diet. Taken together these data confirm that health benefits of CR are conserved in monkeys and suggest that CR mechanisms are likely translatable to human health. PMID:28094793

  17. The Neural Basis of Smooth Pursuit Eye Movements in the Rhesus Monkey Brain

    ERIC Educational Resources Information Center

    Ilg, Uwe J.; Thier, Peter

    2008-01-01

    Smooth pursuit eye movements are performed in order to prevent retinal image blur of a moving object. Rhesus monkeys are able to perform smooth pursuit eye movements quite similar as humans, even if the pursuit target does not consist in a simple moving dot. Therefore, the study of the neuronal responses as well as the consequences of…

  18. Differentiation and characterization of rhesus monkey atrial and ventricular cardiomyocytes from induced pluripotent stem cells.

    PubMed

    Zhang, Xiaoqian; Cao, Henghua; Bai, Shuyun; Huo, Weibang; Ma, Yue

    2017-04-01

    The combination of non-human primate animals and their induced pluripotent stem cell derived cardiomyocytes (iPSC-CMs) provides not only transplantation models for cell-based therapy of heart diseases, but also opportunities for heart-related drug research on both cellular and animal levels. However, the subtypes and electrophysiology properties of non-human primate iPSC-CMs hadn't been detailed characterized. In this study, we generated rhesus monkey induced pluripotent stem cells (riPSCs), and efficiently differentiated them into ventricular or atrial cardiomyocytes by modulating retinoic acid (RA) pathways. Our results revealed that the electrophysiological characteristics and response to canonical drugs of riPSC-CMs were similar with those of human pluripotent stem cell derived CMs. Therefore, rhesus monkeys and their iPSC-CMs provide a powerful and practicable system for heart related biomedical research. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  19. Free-Ranging Rhesus Monkeys Spontaneously Individuate and Enumerate Small Numbers of Non-Solid Portions

    ERIC Educational Resources Information Center

    Wood, Justin N.; Hauser, Marc D.; Glynn, David D.; Barner, David

    2008-01-01

    Fundamental questions in cognitive science concern the origins and nature of the units that compose visual experience. Here, we investigate the capacity to individuate and store information about non-solid portions, asking in particular whether free-ranging rhesus monkeys ("Macaca mulatta") quantify portions of a non-solid substance presented in…

  20. Essentialism in the absence of language? Evidence from rhesus monkeys (Macaca mulatta).

    PubMed

    Phillips, Webb; Shankar, Maya; Santos, Laurie R

    2010-07-01

    We explored whether rhesus monkeys (Macaca mulatta) share one important feature of human essentialist reasoning: the capacity to track category membership across radical featural transformations. Specifically, we examined whether monkeys--like children (Keil, 1989)--expect a transformed object to have the internal properties of its original category. In two experiments, monkeys watched as an experimenter visually transformed a familiar fruit (e.g. apple) into a new kind of fruit (e.g. coconut) either by placing a fruit exterior over the original, or by removing an exterior shell and revealing the inside kind of fruit. The experimenter then pretended to place an inside piece of the transformed fruit into a box which the monkey was allowed to search. Results indicated that monkeys searched the box longer when they found a piece of fruit inconsistent with the inside kind, suggesting that the monkeys expected that the inside of the transformed fruit would taste like the innermost kind they saw. These results suggest that monkeys may share at least one aspect of psychological essentialism: they maintain category-specific expectations about an object's internal properties even when that object's external properties change. These results therefore suggest that some essentialist expectations may emerge in the absence of language, and thus raise the possibility that such tendencies may emerge earlier in human development than has previously been considered.

  1. Vestibuloocular reflex of rhesus monkeys after spaceflight

    NASA Technical Reports Server (NTRS)

    Cohen, Bernard; Kozlovskaia, Inessa; Raphan, Theodore; Solomon, David; Helwig, Denice; Cohen, Nathaniel; Sirota, Mikhail; Iakushin, Sergei

    1992-01-01

    The vestibuloocular reflex (VOR) of two rhesus monkeys was recorded before and after 14 days of spaceflight. The gain (eye velocity/head velocity) of the horizontal VOR, tested 15 and 18 h after landing, was approximately equal to preflight values. The dominant time constant of the animal tested 15 h after landing was equivalent to that before flight. During nystagmus induced by off-vertical axis rotation (OVAR), the latency, rising time constant, steady-state eye velocity, and phase of modulation in eye velocity and eye position with respect to head position were similar in both monkeys before and after flight. There were changes in the amplitude of modulation of horizontal eye velocity during steady-state OVAR and in the ability to discharge stored activity rapidly by tilting during postrotatory nystagmus (tilt dumping) after flight: OVAR modulations were larger, and tilt dumping was lost in the one animal tested on the day of landing and for several days thereafter. If the gain and time constant of the horizontal VOR exchange in microgravity, they must revert to normal soon after landing. The changes that were observed suggest that adaptation to microgravity had caused alterations in way that the central nervous system processes otolith input.

  2. Differences between male and female rhesus monkey erythrocyte acetylcholinesterase and plasma cholinesterase activity before and after exposure to sarin

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Woodard, C.L.; Calamaio, C.A.; Kaminskis, A.

    The female rhesus monkey has a menstrual cycle like the human. Additionally, several differences in enzyme levels between males and females and in the female during the menstrual cycle are present. Therefore we quantitated plasma cholinesterase (ChE/BuChE) and erythrocyte (RBC) acetylcholinesterase (AChE) activity before and after exposure to sarin (GB)(1 5 ug/kg, iv; a 0.75 LD50), in male and female rhesus (Macaca mulatta) monkeys. Twenty-eight-day preexposure baseline plasma ChE and RBC AChE values for six male and six female rhesus monkeys were compared for intra-animal, within sex and between sex differences. After these baseline values were obtained, the organophosphorus (OP)more » compound/Isopropyl methylphosphono-fluoridate (GB) was administered to atropinized monkeys to determine if there was a significant in vivo difference between the sexes in their response to this intoxication in regard to the rate of BuChE /AChE inhibition, pyridine-2-aldoxime methyl chloride (2-PAM) reactivation of the phosphonylated BuChE and the rate of aging of the phosphonylated:BuChE/AChE. In the pre-exposure portion of the protocol; the intra-animal and intra-group BuChE/AChE variations were found to be minimal; but there were significant differences between the male and female monkeys in both plasma BuChE and RBC AChE levels; although probably clinically insignificant in respect to an OP intoxication. No significant cyclic fluctuations were seen during the 28-day study in either sex.« less

  3. Prenatal stress exposure alters postnatal behavioral expression under conditions of novelty challenge in rhesus monkey infants.

    PubMed

    Schneider, M L

    1992-11-01

    This prospective study investigated whether mild maternal stress during pregnancy could alter the behavioral and affective responses in rhesus monkey infants in a complex, novel environment. Twenty-four rhesus monkey infants were tested on three occasions at 6 months of age in a novel environment. Twelve infants were derived from mothers exposed to a daily 10-min mild stressor from Day 90 to Day 145 postconception, while 12 were derived from mothers undisturbed during pregnancy. Prenatally stressed infants demonstrated more disturbance behavior, and lower levels of gross motor/exploratory behavior. Moreover, half of the prenatally stressed infants showed an abnormal response, falling asleep, while none of the control infants displayed this behavior. Males exhibited more clinging to surrogates, while females spent more time in gross motor/exploratory behaviors, with prenatally stressed males tending to spend the least time in gross motor/exploratory activity.

  4. Mother-Infant Attachment, Peer Relationships, and the Development of Social Networks in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Suomi, Stephen J.

    2005-01-01

    The social networks that rhesus monkeys develop in nature are centered around multiple generations of matrilineal kin embedded in larger social groupings that have some degree of distinctiveness and permanence. Within each family, infants initially grow up in the care of their mothers and the close presence of relatives, and they subsequently…

  5. Characterization of glial-restricted precursors from rhesus monkey embryonic stem cells.

    PubMed

    Chen, Hongwei; Mao, Yu; Wang, Shufen; Li, Bin; Wang, Jinhuan; Li, Jian; Ma, Yuanye

    2015-01-01

    Glial-restricted precursor (GRP) cells, the earliest glial progenitors for both astrocytes and oligodendrocytes, have been derived from embryos and embryonic stem cells (ESC) in rodents. However, knowledge regarding the equivalent cell type in primates is limited due to restrictions imposed by ethics and resources. Here we report successful derivation and characterization of primate GRP cells from rhesus monkey ESC. The purified monkey GRP cells were A 2 B 5 -positive and FGF2-dependent for survival and proliferation. The differentiation assays indicated that they were tri-potential in vitro and bi-potential in vivo . These newly purified GRP cells will help to facilitate understanding of the molecular mechanism of glial development in primates as well as provide a source of therapeutic donor cells for use in neuroregenerative medicine.

  6. Pathobiological and Behavioral Effects of Lead Intoxication in the Infant Rhesus Monkey

    PubMed Central

    Allen, J. R.; McWey, P. J.; Suomi, S. J.

    1974-01-01

    When infant rhesus monkeys were exposed to lead via the addition of lead acetate (0.5–9 mg/kg body weight) to their formula or by the consumption of lead particles from lead-based surrogate mothers, they developed symptoms of lead intoxication within 6 weeks. Seizures, muscular tremors, and altered social interaction were the predominant changes. Visual impairment was also apparent in the more severely affected animals. In the animals showing obvious symptoms lead levels varied between 300 to 500 μg/100 ml of blood. Even in those animals having blood lead levels below 100 μg, hyperactivity and insomnia were observed. When the exposure to lead was eliminated, seizures subsided and visual impairment was reduced; however, the abnormal social interaction persisted. These animals also experienced a gradual decline in hematocrit and hemoglobin values during the period of examination. Liver and kidney biopsies obtained from these lead-exposed animals revealed characteristic intranuclear inclusions. When adolescent and adult monkeys were exposed to doses of lead acetate similar to those employed in the infant experiments, lead levels in excess of 200 μg/100 ml of blood were recorded. However, there were no obvious behavioral abnormalities observed. There were, however, numerous lead inclusion bodies in kidney biopsy specimens from these animals. These data suggest that, like man, the infant nonhuman primate is much more susceptible to lead intoxication than is the adult. The clinical and behavioral changes recorded in these infant rhesus monkeys suggest their use as an experimental model to evaluate lead intoxication. ImagesFIGURE 6. PMID:4208658

  7. Age-related alterations of plasma glutathione and oxidation of redox potentials in chimpanzee (Pan troglodytes) and rhesus monkey (Macaca mulatta).

    PubMed

    Paredes, Jamespaul; Jones, Dean P; Wilson, Mark E; Herndon, James G

    2014-04-01

    Chimpanzee (Pan troglodytes) and rhesus macaque (Macaca mulatta) and humans (Homo sapiens) share physiological and genetic characteristics, but have remarkably different life spans, with chimpanzees living 50-60 % and the rhesus living 35-40 % of maximum human survival. Since oxidative processes are associated with aging and longevity, we might expect to see species differences in age-related oxidative processes. Blood and extracellular fluid contain two major thiol redox nodes, glutathione (GSH)/glutathione-disulfide (GSSG) and cysteine (Cys)/cystine (CySS), which are subject to reversible oxidation-reduction reactions and are maintained in a dynamic non-equilibrium state. Disruption of these thiol redox nodes leads to oxidation of their redox potentials (EhGSSG and EhCySS) which affects cellular physiology and is associated with aging and the development of chronic diseases in humans. The purpose of this study was to measure age-related changes in these redox thiols and their corresponding redox potentials (Eh) in chimpanzees and rhesus monkeys. Our results show similar age-related decreases in the concentration of plasma GSH and Total GSH as well as oxidation of the EhGSSG in male and female chimpanzees. Female chimpanzees and female rhesus monkeys also were similar in several outcome measures. For example, similar age-related decreases in the concentration of plasma GSH and Total GSH, as well as age-related oxidation of the EhGSSG were observed. The data collected from chimpanzees and rhesus monkeys corroborates previous reports on oxidative changes in humans and confirms their value as a comparative reference for primate aging.

  8. Real-time bioluminescence imaging of macroencapsulated fibroblasts reveals allograft protection in rhesus monkeys (Macaca mulatta).

    PubMed

    Tarantal, Alice F; Lee, C Chang I; Itkin-Ansari, Pamela

    2009-07-15

    Encapsulation of cells has the potential to eliminate the need for immunosuppression for cellular transplantation. Recently, the TheraCyte device was shown to provide long-term immunoprotection of murine islets in a mouse model of diabetes. In this report, translational studies were undertaken using skin fibroblasts from an unrelated rhesus monkey donor that were transduced with an HIV-1-derived lentiviral vector expressing firefly luciferase permitting the use of bioluminescence imaging (BLI) to monitor cell survival over time and in a noninvasive manner. Encapsulated cells were transplanted subcutaneously (n=2), or cells were injected without encapsulation (n=1) and outcomes compared. BLI was performed to monitor cell survival. The BLI signal from the encapsulated cells remained robust postinsertion and in one animal persisted for up to 1 year. In contrast, the control animal that received unencapsulated cells exhibited a complete loss of cell signal within 14 days. These data demonstrate that TheraCyte encapsulation of allogeneic cells provides robust immune protection in transplanted rhesus monkeys.

  9. Handedness influences intermanual transfer in chimpanzees (Pan troglodytes) but not rhesus monkeys (Macaca mulatta).

    PubMed

    Boeving, Emily R; Lacreuse, Agnès; Hopkins, William D; Phillips, Kimberley A; Novak, Melinda A; Nelson, Eliza L

    2015-03-01

    Intermanual transfer refers to an effect, whereby training one hand to perform a motor task improves performance in the opposite untrained hand. We tested the hypothesis that handedness facilitates intermanual transfer in two nonhuman primate species: rhesus monkeys (N = 13) and chimpanzees (N = 52). Subjects were grouped into one of four conditions: (1) left-handers trained with the left (dominant) hand; (2) left-handers trained with the right (nondominant) hand; (3) right-handers trained with the left (nondominant) hand; and (4) right-handers trained with the right (dominant) hand. Intermanual transfer was measured using a task where subjects removed a Life Savers(®) candy (monkeys) or a washer (chimpanzees) from metal shapes. Transfer was measured with latency by comparing the average time taken to solve the task in the first session with the trained hand compared to the first session with the untrained hand. Hypotheses and predictions were derived from three models of transfer: access: benefit training with nondominant hand; proficiency: benefit training with dominant hand; and cross-activation: benefit irrespective of trained hand. Intermanual transfer (i.e., shorter latency in untrained hand) occurred regardless of whether monkeys trained with the dominant hand or nondominant hand, supporting the cross-activation model. However, transfer was only observed in chimpanzees that trained with the dominant hand. When handedness groups were examined separately, the transfer effect was only significant for right-handed chimpanzees, partially supporting the proficiency model. Findings may be related to neurophysiological differences in motor control as well as differences in handedness patterning between rhesus monkeys and chimpanzees.

  10. Handedness influences intermanual transfer in chimpanzees (Pan troglodytes) but not rhesus monkeys (Macaca mulatta)

    PubMed Central

    Boeving, Emily R.; Lacreuse, Agnès; Hopkins, William D.; Phillips, Kimberley A.; Novak, Melinda A.; Nelson, Eliza L.

    2015-01-01

    Intermanual transfer refers to an effect whereby training one hand to perform a motor task improves performance in the opposite untrained hand. We tested the hypothesis that handedness facilitates intermanual transfer in two nonhuman primate species: rhesus monkeys (N = 13) and chimpanzees (N = 52). Subjects were grouped into one of four conditions: (1) left-handers trained with the left (dominant) hand; (2) left-handers trained with the right (non-dominant) hand; (3) right-handers trained with the left (non-dominant) hand; and (4) right-handers trained with the right (dominant) hand. Intermanual transfer was measured using a task where subjects removed a Life Savers® candy (monkeys) or a washer (chimpanzees) from metal shapes. Transfer was measured with latency by comparing the average time taken to solve the task in the first session with the trained hand compared to the first session with the untrained hand. Hypotheses and predictions were derived from three models of transfer: access: benefit training with non-dominant hand; proficiency: benefit training with dominant hand; and cross-activation: benefit irrespective of trained hand. Intermanual transfer (i.e., shorter latency in untrained hand) occurred regardless of whether monkeys trained with the dominant hand or non-dominant hand, supporting the cross-activation model. However, transfer was only observed in chimpanzees that trained with the dominant hand. When handedness groups were examined separately, the transfer effect was only significant for right-handed chimpanzees, partially supporting the proficiency model. Findings may be related to neurophysiological differences in motor control as well as differences in handedness patterning between rhesus monkeys and chimpanzees. PMID:25466868

  11. Rhesus monkeys (Macaca mulatta) remember agency information from past events and integrate this knowledge with spatial and temporal features in working memory.

    PubMed

    Hoffman, Megan L; Beran, Michael J; Washburn, David A

    2018-01-01

    The purpose of the present study was to examine whether rhesus monkeys remember information about their own agency-along with spatial, temporal and contextual properties-from a previously experienced event. In Experiment 1, rhesus monkeys (n = 4) used symbols to reliably indicate whether they had performed or observed an event on a computer screen. In Experiment 2, naïve and experienced monkeys (n = 8) reported agency information when stringent controls for perceptual and proprioceptive cues were included. In Experiment 3, five of the monkeys completed a task in which they reported agency information along with spatial and temporal features of events. Two monkeys performed this agency discrimination when they could not anticipate which memory test they would receive. There was also evidence that these features were integrated in memory. Implications of this research are discussed in relation to working memory, episodic memory and self-awareness in nonhuman animals.

  12. What interests them in the pictures?--differences in eye-tracking between rhesus monkeys and humans.

    PubMed

    Hu, Ying-Zhou; Jiang, Hui-Hui; Liu, Ci-Rong; Wang, Jian-Hong; Yu, Cheng-Yang; Carlson, Synnöve; Yang, Shang-Chuan; Saarinen, Veli-Matti; Rizak, Joshua D; Tian, Xiao-Guang; Tan, Hen; Chen, Zhu-Yue; Ma, Yuan-Ye; Hu, Xin-Tian

    2013-10-01

    Studies estimating eye movements have demonstrated that non-human primates have fixation patterns similar to humans at the first sight of a picture. In the current study, three sets of pictures containing monkeys, humans or both were presented to rhesus monkeys and humans. The eye movements on these pictures by the two species were recorded using a Tobii eye-tracking system. We found that monkeys paid more attention to the head and body in pictures containing monkeys, whereas both monkeys and humans paid more attention to the head in pictures containing humans. The humans always concentrated on the eyes and head in all the pictures, indicating the social role of facial cues in society. Although humans paid more attention to the hands than monkeys, both monkeys and humans were interested in the hands and what was being done with them in the pictures. This may suggest the importance and necessity of hands for survival. Finally, monkeys scored lower in eye-tracking when fixating on the pictures, as if they were less interested in looking at the screen than humans. The locations of fixation in monkeys may provide insight into the role of eye movements in an evolutionary context.

  13. Rhesus Monkeys (Macaca Mulatta) Demonstrate Robust Memory for What and Where, but Not When, in an Open-Field Test of Memory

    ERIC Educational Resources Information Center

    Hampton, R.R.; Hampstead, B.M.; Murray, E.A.

    2005-01-01

    We adapted a paradigm developed by Clayton and Dickinson (1998), who demonstrated memory for what, where, and when in scrub jays, for use with rhesus monkeys. In the study phase of each trial, monkeys found a preferred and a less-preferred food reward in a trial-unique array of three locations in a large room. After 1h, monkeys returned to the…

  14. Vestibular afferent responses to linear accelerations in the alert squirrel monkey

    NASA Technical Reports Server (NTRS)

    Somps, Christopher J.; Schor, Robert H.; Tomko, David L.

    1994-01-01

    The spontaneous activity of 40 otolith afferents and 44 canal afferents was recorded in 4 alert, intact squirrel monkeys. Polarization vectors and response properties of otolith afferents were determined during static re-orientations relative to gravity and during Earth-horizontal, sinusoidal, linear oscillations. Canal afferents were tested for sensitivity to linear accelerations. For regular otolith afferents, a significant correlation between upright discharge rate and sensitivity to dynamic acceleration in the horizontal plane was observed. This correlation was not present in irregular units. The sensitivity of otolith afferents to both static tilts and dynamic linear acceleration was much greater in irregularly discharging units than in regularly discharging units. The spontaneous activity and static and dynamic response properties of regularly discharging otolith afferents were similar to those reported in barbiturate-anesthetized squirrel monkeys. Irregular afferents also had similar dynamic response properties when compared to anesthetized monkeys. However, this sample of irregular afferents in alert animals had higher resting discharge rates and greater sensitivity to static tilts. The majority of otolith polarization vectors were oriented near the horizontal in the plane of the utricular maculae; however, directions of maximum sensitivity were different during dynamic and static testing. Canal afferents were not sensitive to static tilts or linear oscillations of the head.

  15. Evidence for Motor Planning in Monkeys: Rhesus Macaques Select Efficient Grips when Transporting Spoons

    ERIC Educational Resources Information Center

    Nelson, Eliza L.; Berthier, Neil E.; Metevier, Christina M.; Novak, Melinda A.

    2011-01-01

    McCarty and colleagues (1999) developed the elevated spoon task to measure motor planning in human infants. In this task, a spoon containing food was placed on an elevated apparatus that supported both ends of the spoon. The handle was oriented to the left or right on different trials. We presented naive adult rhesus monkeys (Macaca mulatta) with…

  16. Placental Transport of Zidovudine in the Rhesus Monkey

    PubMed Central

    King, Thomas S.; Henderson, George I.; Schenker, Steven; Schenken, Robert S.

    1993-01-01

    Objective: This study was undertaken to characterize the pharmacokinetics of zidovudine (ZDV) and ZDV-glucuronide (ZDVG) in the material and :fetal circulations of the rhesus monkey. Methods: Cannulas were placed in the maternal external jugular and the fetal internal jugular and carotid artery in 8 pregnant monkeys at .120–130 days gestation. ZDV (3.5 mg/kg) was administered to 5 monkeys and ZDVG (3.5 mg/kg) to 3 monkeys as single intravenous bolus infusions through the maternal catheter. Maternal and fetal blood , samples were collected every 20 min for the first 2 h and then every hour for the next 4 h. Maternal and fetal concentrations of ZDV and ZDVG were determined using high, performance liquid chromatography (HPLC) with ultraviolet (UV) detection. Results: In monkeys who received ZDV, the terminal half-life (T1/2) for ZDV was 37±15 and 33 ± 13 min in the maternal and fetal compartments, respectively. The apparent T1/2 for maternal ZDVG was 124 ± 44 and 142 ± 50 min in the maternal and fetal compartments, respectively. Peak levels of ZDV and ZDVG in the fetal compartment were reached 40 min after injection. The mean fetal/maternal concentration ratios for ZDV and ZDVG ranged from 0.20 ± 0.20 at 20 min to a maximum of 0.74 ± 1.0 at 120 min and from 0.28 ± 0.08 at 20 min to 1.4 ± 1.3 at 180 min, respectively. In monkeys who received ZDVG, the T1/2 for ZDWG in the maternal and fetal compartments was 47 ± 26 and 119 ± 164 min, respectively. ZDVG reached its peak in the fetal compartment at 60 min post-injection. The fetal/maternal rafio ranged from 0.08 ± 0.11 at 20 min to 4.2 ± 4.2 at 180 min post-injection. Conclusions: These data demonstrate that 1) ZDV and ZDVG rapidly cross the placenta to the fetal compartment, 2) ZDV crosses more rapidly than ZDVG, and 3) some metabolism of ZDV to ZDVG occurs in the fetal compartment. PMID:18475334

  17. Two processes support visual recognition memory in rhesus monkeys

    PubMed Central

    Guderian, Sebastian; Brigham, Danielle; Mishkin, Mortimer

    2011-01-01

    A large body of evidence in humans suggests that recognition memory can be supported by both recollection and familiarity. Recollection-based recognition is characterized by the retrieval of contextual information about the episode in which an item was previously encountered, whereas familiarity-based recognition is characterized instead by knowledge only that the item had been encountered previously in the absence of any context. To date, it is unknown whether monkeys rely on similar mnemonic processes to perform recognition memory tasks. Here, we present evidence from the analysis of receiver operating characteristics, suggesting that visual recognition memory in rhesus monkeys also can be supported by two separate processes and that these processes have features considered to be characteristic of recollection and familiarity. Thus, the present study provides converging evidence across species for a dual process model of recognition memory and opens up the possibility of studying the neural mechanisms of recognition memory in nonhuman primates on tasks that are highly similar to the ones used in humans. PMID:22084079

  18. Contextual Factors Explain Risk-Seeking Preferences in Rhesus Monkeys

    PubMed Central

    Heilbronner, Sarah R.; Hayden, Benjamin Y.

    2012-01-01

    In contrast to humans and most other animals, rhesus macaques strongly prefer risky rewards to safe ones with similar expected value. Why macaques prefer risk while other animals typically avoid it remains puzzling and challenges the idea that monkeys provide a model for human economic behavior. Here we argue that monkeys’ risk-seeking preferences are neither mysterious nor unique. Risk-seeking in macaques is possibly induced by specific elements of the tasks that have been used to measure their risk preferences. The most important of these elements are (1) very small stakes, (2) serially repeated gambles with short delays between trials, and (3) task parameters that are learned through experience, not described verbally. Together, we hypothesize that these features will readily induce risk-seeking in monkeys, humans, and rats. Thus, elements of task design that are often ignored when comparing studies of risk attitudes can easily overwhelm basal risk preferences. More broadly, these results highlight the fundamental importance of understanding the psychological basis of economic decisions in interpreting preference data and corresponding neural measures. PMID:23378827

  19. Effects of Aroclor 1254 reg sign on hydrocortisone levels in adult Rhesus monkeys (Macaca mulatta)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Loo, J.C.K.; Tryphonas, H.; Jordan, N.

    Researchers, using female Sprague Dawley rats, reported the effects of chronic (5-7 months) oral dosing with Aroclor 1254{reg sign} (Polychlorinated biphenyls-PCB) on the serum levels of corticosterone, the principle glucocorticoid in rats. Their findings indicated that corticosterone levels were significantly depressed at dose levels of 479 {mu}g/kg bw/day and above. The objective of the present study was to determine the effects of PCB on the hydrocortisone levels in Rhesus monkey (Macaca mulatta) serum. In the monkey the controlling hormone is hydrocortisone which is identical to that of humans.

  20. Topical and intravenous pilocarpine stimulated accommodation in anesthetized rhesus monkeys.

    PubMed

    Wendt, Mark; Glasser, Adrian

    2010-05-01

    Many studies have used pilocarpine to stimulate accommodation in both humans and monkeys. However, the concentrations of pilocarpine used and the methods of administration vary. In this study, three different methods of pilocarpine administration are evaluated for their effectiveness in stimulating accommodation in rhesus monkeys. Experiments were performed in 17 iridectomized, anesthetized rhesus monkeys aged 4-16 years. Maximum accommodation was stimulated in all these monkeys with a 2% pilocarpine solution maintained on the cornea for at least 30 min in a specially designed perfusion lens. In subsequent topical pilocarpine experiments, baseline refraction was measured with a Hartinger coincidence refractometer and then while the monkeys were upright and facing forward, commercially available pilocarpine (2, 4, or 6%) was applied topically to the cornea as 2 or 4 drops in two applications or 6 drops in three applications over a five minute period with the eyelids closed between applications. Alternatively, while supine, 10-12 drops of pilocarpine were maintained on the cornea in a scleral cup for 5 min. Refraction measurements were begun 5 min after the second application of pilocarpine and continued for at least 30 min after initial administration until no further change in refraction occurred. In intravenous experiments, pilocarpine was given either as boluses ranging from 0.1mg/kg to 2mg/kg or boluses followed by a constant infusion at rates between 3.06 mg/kg/h and 11.6 mg/kg/h. Constant 2% pilocarpine solution on the eye in the perfusion lens produced 10.88+/-2.73 D (mean+/-SD) of accommodation. Topically applied pilocarpine produced 3.81 D+/-2.41, 5.49 D+/-4.08, and 5.55 D+/-3.27 using 2%, 4%, and 6% solutions respectively. When expressed as a percentage of the accommodative response amplitude obtained in the same monkey with constant 2% pilocarpine solution on the eye, the responses were 34.7% for 2% pilocarpine, 48.4% for 4% pilocarpine, and 44.6% for 6

  1. Pharmacokinetics and safety in rhesus monkeys of a monoclonal antibody-GDNF fusion protein for targeted blood-brain barrier delivery.

    PubMed

    Pardridge, William M; Boado, Ruben J

    2009-10-01

    Glial-derived neurotrophic factor (GDNF) is a potential therapy for stroke, Parkinson's disease, or drug addiction. However, GDNF does not cross the blood-brain barrier (BBB). GDNF is re-engineered as a fusion protein with a chimeric monoclonal antibody (MAb) to the human insulin receptor (HIR), which acts as a molecular Trojan horse to deliver the GDNF across the BBB. The pharmacokinetics (PK), toxicology, and safety pharmacology of the HIRMAb-GDNF fusion protein were investigated in Rhesus monkeys. The fusion protein was administered as an intravenous injection at doses up to 50 mg/kg over a 60 h period to 56 Rhesus monkeys. The plasma concentration of the HIRMAb-GDNF fusion protein was measured with a 2-site sandwich ELISA. No adverse events were observed in a 2-week terminal toxicology study, and no neuropathologic changes were observed. The PK analysis showed a linear relationship between plasma AUC and dose, a large systemic volume of distribution, as well as high clearance rates of 8-10 mL/kg/min. A no-observable-adverse-effect level is established in the Rhesus monkey for the acute administration of the HIRMAb-GDNF fusion protein. The fusion protein targeting the insulin receptor has a PK profile similar to a classical small molecule.

  2. Behavioral consequences of developmental iron deficiency in infant rhesus monkeys

    PubMed Central

    Golub, Mari S.; Hogrefe, Casey E.; Germann, Stacey L.; Capitanio, John P.; Lozoff, Betsy

    2006-01-01

    Human studies have shown that iron deficiency and iron deficiency anemia in infants are associated with behavioral impairment, but the periods of brain development most susceptible to iron deficiency have not been established. In the present study, rhesus monkeys were deprived of iron by dietary iron restriction during prenatal (n = 14, 10 μg Fe/g diet) or early postnatal (n = 12, 1.5 mg Fe/L formula) brain development and compared to controls (n = 12, 100 μg Fe/g diet, 12 mg Fe/L formula) in behavioral evaluations conducted during the first four months of life in the nonhuman primate nursery. Iron deficiency anemia was detected in the pregnant dams in the third trimester and compromised iron status was seen in the prenatally iron-deprived infants at birth, but no iron deficiency was seen in either the prenatally or postnatally iron-deprived infants during the period of behavioral evaluation. Neither prenatal nor postnatal iron deprivation led to significant delays in growth, or gross or fine motor development. Prenatally deprived infants demonstrated a 20% reduced spontaneous activity level, lower inhibitory response to novel environments, and more changes from one behavior to another in weekly observation sessions. Postnatally deprived infants demonstrated poorer performance of an object concept task, and greater emotionality relative to controls. This study indicates that different syndromes of behavioral effects are associated with prenatal and postnatal iron deprivation in rhesus monkey infants and that these effects can occur in the absence of concurrent iron deficiency as reflected in hematological measures. PMID:16343844

  3. Intranasal oxytocin selectively attenuates rhesus monkeys' attention to negative facial expressions.

    PubMed

    Parr, Lisa A; Modi, Meera; Siebert, Erin; Young, Larry J

    2013-09-01

    Intranasal oxytocin (IN-OT) modulates social perception and cognition in humans and could be an effective pharmacotherapy for treating social impairments associated with neuropsychiatric disorders, like autism. However, it is unknown how IN-OT modulates social cognition, its effect after repeated use, or its impact on the developing brain. Animal models are urgently needed. This study examined the effect of IN-OT on social perception in monkeys using tasks that reveal some of the social impairments seen in autism. Six rhesus macaques (Macaca mulatta, 4 males) received a 48 IU dose of OT or saline placebo using a pediatric nebulizer. An hour later, they performed a computerized task (the dot-probe task) to measure their attentional bias to social, emotional, and nonsocial images. Results showed that IN-OT significantly reduced monkeys' attention to negative facial expressions, but not neutral faces or clip art images and, additionally, showed a trend to enhance monkeys' attention to direct vs. averted gaze faces. This study is the first to demonstrate an effect of IN-OT on social perception in monkeys, IN-OT selectively reduced monkey's attention to negative facial expressions, but not neutral social or nonsocial images. These findings complement several reports in humans showing that IN-OT reduces the aversive quality of social images suggesting that, like humans, monkey social perception is mediated by the oxytocinergic system. Importantly, these results in monkeys suggest that IN-OT does not dampen the emotional salience of social stimuli, but rather acts to affect the evaluation of emotional images during the early stages of information processing. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. Rhesus Monkeys Behave As If They Perceive the Duncker Illusion

    PubMed Central

    Zivotofsky, A. Z.; Goldberg, M. E.; Powell, K. D.

    2008-01-01

    The visual system uses the pattern of motion on the retina to analyze the motion of objects in the world, and the motion of the observer him/herself. Distinguishing between retinal motion evoked by movement of the retina in space and retinal motion evoked by movement of objects in the environment is computationally difficult, and the human visual system frequently misinterprets the meaning of retinal motion. In this study, we demonstrate that the visual system of the Rhesus monkey also misinterprets retinal motion. We show that monkeys erroneously report the trajectories of pursuit targets or their own pursuit eye movements during an epoch of smooth pursuit across an orthogonally moving background. Furthermore, when they make saccades to the spatial location of stimuli that flashed early in an epoch of smooth pursuit or fixation, they make large errors that appear to take into account the erroneous smooth eye movement that they report in the first experiment, and not the eye movement that they actually make. PMID:16102233

  5. Population density-dependent hair cortisol concentrations in rhesus monkeys (Macaca mulatta)

    PubMed Central

    Dettmer, A.M.; Novak, M.A.; Meyer, J.S.; Suomi, S.J.

    2014-01-01

    Summary Population density is known to influence acute measures of hypothalamic-pituitary-adrenal (HPA) axis activity in a variety of species, including fish, deer, birds, and humans. However, the effects of population density on levels of chronic stress are unknown. Given the fact that exposure to chronically elevated levels of circulating glucocorticoids results in a host of health disparities in animals and humans alike, it is important to understand how population density may impact chronic stress. We assessed hair cortisol concentrations (HCCs), which are reliable indicators of chronic HPA axis activity, in rhesus monkeys (Macaca mulatta) to determine the influence of population density on these values. In Experiment 1, we compared HCCs of monkeys living in high-density (HD; 1 monkey/0.87m2) and low-density (LD; 1 monkey/63.37m2) environments (N=236 hair samples) and found that HD monkeys exhibited higher hair cortisol across all age categories (infant, juvenile, young adult, adult, and aged) except infancy and aged (F(5)=4.240, p=0.001), for which differences were nearly significant. HD monkeys also received more severe fight wounds than LD monkeys (χ2=26.053, p<0.001), though no effects of dominance status emerged. In Experiment 2, we examined how HCCs change with fluctuating population levels across five years in the adult LD monkeys (N=155 hair samples) and found that increased population density was significantly positively correlated with HCCs in this semi-naturalistic population (r(s)=0.975, p=0.005). These are the first findings to demonstrate that increased population density is associated with increased chronic, endogenous glucocorticoid exposure in a nonhuman primate species. We discuss the implications of these findings with respect to laboratory research, population ecology, and human epidemiology. PMID:24636502

  6. Population density-dependent hair cortisol concentrations in rhesus monkeys (Macaca mulatta).

    PubMed

    Dettmer, A M; Novak, M A; Meyer, J S; Suomi, S J

    2014-04-01

    Population density is known to influence acute measures of hypothalamic-pituitary-adrenal (HPA) axis activity in a variety of species, including fish, deer, birds, and humans. However, the effects of population density on levels of chronic stress are unknown. Given the fact that exposure to chronically elevated levels of circulating glucocorticoids results in a host of health disparities in animals and humans alike, it is important to understand how population density may impact chronic stress. We assessed hair cortisol concentrations (HCCs), which are reliable indicators of chronic HPA axis activity, in rhesus monkeys (Macaca mulatta) to determine the influence of population density on these values. In Experiment 1, we compared HCCs of monkeys living in high-density (HD; 1 monkey/0.87m(2)) and low-density (LD; 1 monkey/63.37m(2)) environments (N=236 hair samples) and found that HD monkeys exhibited higher hair cortisol across all age categories (infant, juvenile, young adult, adult, and aged) except infancy and aged (F(5)=4.240, p=0.001), for which differences were nearly significant. HD monkeys also received more severe fight wounds than LD monkeys (χ(2)=26.053, p<0.001), though no effects of dominance status emerged. In Experiment 2, we examined how HCCs change with fluctuating population levels across 5 years in the adult LD monkeys (N=155 hair samples) and found that increased population density was significantly positively correlated with HCCs in this semi-naturalistic population (r(s)=0.975, p=0.005). These are the first findings to demonstrate that increased population density is associated with increased chronic, endogenous glucocorticoid exposure in a nonhuman primate species. We discuss the implications of these findings with respect to laboratory research, population ecology, and human epidemiology. Published by Elsevier Ltd.

  7. Thermoregulatory responses of rhesus monkeys during spaceflight

    NASA Technical Reports Server (NTRS)

    Sulzman, F. M.; Ferraro, J. S.; Fuller, C. A.; Moore-Ede, M. C.; Klimovitsky, V.; Magedov, V.; Alpatov, A. M.

    1992-01-01

    This study examines the activity, axillary temperature (T(ax)), and ankle skin temperature (Tsk) of two male Rhesus monkeys exposed to microgravity in space. The animals were flown on a Soviet biosatellite mission (COSMOS 1514). Measurements on the flight animals, as well as synchronous flight controls, were performed in the Soviet Union. Additional control studies were performed in the United States to examine the possible role of metabolic heat production in the T(ax) response observed during the spaceflight. All monkeys were exposed to a 24-h light-dark cycle (LD 16:8) throughout these studies. During weightlessness, T(ax) in both flight animals was lower than on earth. The largest difference (0.75 degree C) occurred during the night. There was a reduction in mean heart rate and Tsk during flight. This suggests a reduction in both heat loss and metabolic rate during spaceflight. Although the circadian rhythms in all variables were present during flight, some differences were noted. For example, the amplitude of the rhythms in Tsk and activity were attenuated. Furthermore, the T(ax) and activity rhythms did not have precise 24.0 hour periods and may have been externally desynchronized from the 24-h LD cycle. These data suggest a weakening of the coupling between the internal circadian pacemaker and the external LD synchronizer.

  8. EVIDENCE FOR MOTOR PLANNING IN MONKEYS: RHESUS MACAQUES SELECT EFFICIENT GRIPS WHEN TRANSPORTING SPOONS

    PubMed Central

    Nelson, Eliza L.; Berthier, Neil E.; Metevier, Christina M.; Novak, Melinda A.

    2014-01-01

    McCarty and colleagues (1999) developed the elevated spoon task to measure motor planning in human infants. In this task, a spoon containing food was placed on an elevated apparatus that supported both ends of the spoon. The handle was oriented to the left or right on different trials. We presented naïve adult rhesus monkeys (Macaca mulatta) with the elevated spoon problem, and observed how monkeys learned the affordances of spoons over sessions. Strikingly, monkeys developed two different strategies for efficient spoon transport in just 12 to 36 trials. In subsequent testing with a novel double bowl spoon approximately 1 year later, monkeys demonstrated that they were attending to the baited spoon bowl and continued to select efficient grips for transporting the spoon. Monkey data were contrasted with previous studies in human infants using a perception-action perspective in an effort to understand the fundamentals of tool use and motor planning that may be common in the development of these abilities across species and their origins in human behavior. PMID:21676101

  9. Peer social interaction is facilitated in juvenile rhesus monkeys treated with fluoxetine.

    PubMed

    Golub, Mari S; Hogrefe, Casey E; Bulleri, Alicia M

    2016-06-01

    Fluoxetine improves social interactions in children with autism, social anxiety and social phobia. It is not known whether this effect is mediated directly or indirectly by correcting the underlying pathology. Genetics may also influence the drug effect. Polymorphisms of the MAOA (monoamine oxidase A) gene interact with fluoxetine to influence metabolic profiles in juvenile monkeys. Juvenile nonhuman primates provide an appropriate model for studying fluoxetine effects and drug*gene interactions in children. Male rhesus monkeys 1-3 years of age living in permanent social pairs were treated daily with a therapeutic dose of fluoxetine or vehicle (n = 16/group). Both members of each social pair were assigned to the same treatment group. They were observed for social interactions with their familiar cagemate over a 2-year dosing period. Subjects were genotyped for MAOA variable number of tandem repeats (VNTR) polymorphisms categorized for high or low transcription rates (hi-MAOA, low-MAOA). Fluoxetine-treated animals spent 30% more time in social interaction than vehicle controls. Fluoxetine significantly increased the duration of quiet interactions, the most common type of interaction, and also of immature sexual behavior typical of rhesus in this age group. Specific behaviors affected depended on MAOA genotype of the animal and its social partner. When given fluoxetine, hi-MOAO monkeys had more social invitation and initiation behaviors and low-MAOA subjects with low-MAOA partners had more grooming and an increased frequency of some facial and vocal expressive behaviors. Fluoxetine may facilitate social interaction in children independent of remediation of psychopathology. Common genetic variants may modify this effect. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Peer social interaction is facilitated in juvenile rhesus monkeys treated with fluoxetine

    PubMed Central

    Golub, Mari S.; Hogrefe, Casey E.; Bulleri, Alicia M.

    2016-01-01

    Background Fluoxetine improves social interactions in children with autism, social anxiety and social phobia. It is not known whether this effect is mediated directly or indirectly by correcting the underlying pathology. Genetics may also influence the drug effect. Polymorphisms of the MAOA (monoamine oxidase A) gene interact with fluoxetine to influence metabolic profiles in juvenile monkeys. Juvenile nonhuman primates provide an appropriate model for studying fluoxetine effects and drug*gene interactions in children. Methods Male rhesus monkeys 1–3 years of age living in permanent social pairs were treated daily with a therapeutic dose of fluoxetine or vehicle (n=16/group). Both members of each social pair were assigned to the same treatment group. They were observed for social interactions with their familiar cagemate over a 2-year dosing period. Subjects were genotyped for MAOA variable number of tandem repeats (VNTR) polymorphisms categorized for high or low transcription rates (hi-MAOA, low-MAOA). Results Fluoxetine-treated animals spent 30% more time in social interaction than vehicle controls. Fluoxetine significantly increased the duration of quiet interactions, the most common type of interaction, and also of immature sexual behavior typical of rhesus in this age group. Specific behaviors affected depended on MAOA genotype of the animal and its social partner. When given fluoxetine, hi-MOAO monkeys had more social invitations and initiation behaviors and low-MAOA subjects with low-MAOA partners had more grooming and an increased frequency of some facial and vocal expressive behaviors. Conclusions Fluoxetine may facilitate social interaction in children independent of remediation of psychopathology. Common genetic variants may modify this effect. PMID:26905291

  11. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys.

    PubMed

    Xu, Ning; Kwon, Soonil; Abbott, David H; Geller, David H; Dumesic, Daniel A; Azziz, Ricardo; Guo, Xiuqing; Goodarzi, Mark O

    2011-01-01

    The pathogenesis of polycystic ovary syndrome (PCOS) is poorly understood. PCOS-like phenotypes are produced by prenatal androgenization (PA) of female rhesus monkeys. We hypothesize that perturbation of the epigenome, through altered DNA methylation, is one of the mechanisms whereby PA reprograms monkeys to develop PCOS. Infant and adult visceral adipose tissues (VAT) harvested from 15 PA and 10 control monkeys were studied. Bisulfite treated samples were subjected to genome-wide CpG methylation analysis, designed to simultaneously measure methylation levels at 27,578 CpG sites. Analysis was carried out using Bayesian Classification with Singular Value Decomposition (BCSVD), testing all probes simultaneously in a single test. Stringent criteria were then applied to filter out invalid probes due to sequence dissimilarities between human probes and monkey DNA, and then mapped to the rhesus genome. This yielded differentially methylated loci between PA and control monkeys, 163 in infant VAT, and 325 in adult VAT (BCSVD P<0.05). Among these two sets of genes, we identified several significant pathways, including the antiproliferative role of TOB in T cell signaling and transforming growth factor-β (TGF-β) signaling. Our results suggest PA may modify DNA methylation patterns in both infant and adult VAT. This pilot study suggests that excess fetal androgen exposure in female nonhuman primates may predispose to PCOS via alteration of the epigenome, providing a novel avenue to understand PCOS in humans.

  12. Action Categorization in Rhesus Monkeys: discrimination of grasping from non-grasping manual motor acts.

    PubMed

    Nelissen, Koen; Vanduffel, Wim

    2017-11-08

    The ability to recognize others' actions is an important aspect of social behavior. While neurophysiological and behavioral research in monkeys has offered a better understanding of how the primate brain processes this type of information, further insight with respect to the neural correlates of action recognition requires tasks that allow recording of brain activity or perturbing brain regions while monkeys simultaneously make behavioral judgements about certain aspects of observed actions. Here we investigated whether rhesus monkeys could actively discriminate videos showing grasping or non-grasping manual motor acts in a two-alternative categorization task. After monkeys became proficient in this task, we tested their ability to generalize to a number of untrained, novel videos depicting grasps or other manual motor acts. Monkeys generalized to a wide range of novel human or conspecific grasping and non-grasping motor acts. They failed, however, for videos showing unfamiliar actions such as a non-biological effector performing a grasp, or a human hand touching an object with the back of the hand. This study shows the feasibility of training monkeys to perform active judgements about certain aspects of observed actions, instrumental for causal investigations into the neural correlates of action recognition.

  13. Visual Short-Term Memory Compared in Rhesus Monkeys and Humans

    PubMed Central

    Elmore, L. Caitlin; Ma, Wei Ji; Magnotti, John F.; Leising, Kenneth J.; Passaro, Antony D.; Katz, Jeffrey S.; Wright, Anthony A.

    2011-01-01

    Summary Change detection is a popular task to study visual short-term memory (STM) in humans [1–4]. Much of this work suggests that STM has a fixed capacity of 4 ± 1 items [1–6]. Here we report the first comparison of change detection memory between humans and a species closely related to humans, the rhesus monkey. Monkeys and humans were tested in nearly identical procedures with overlapping display sizes. Although the monkeys’ STM was well fit by a 1-item fixed-capacity memory model, other monkey memory tests with 4-item lists have shown performance impossible to obtain with a 1-item capacity [7]. We suggest that this contradiction can be resolved using a continuous-resource approach more closely tied to the neural basis of memory [8,9]. In this view, items have a noisy memory representation whose noise level depends on display size due to distributed allocation of a continuous resource. In accord with this theory, we show that performance depends on the perceptual distance between items before and after the change, and d′ depends on display size in an approximately power law fashion. Our results open the door to combining the power of psychophysics, computation, and physiology to better understand the neural basis of STM. PMID:21596568

  14. Behavioral responses of trained squirrel and rhesus monkeys during oculomotor tasks

    PubMed Central

    Heiney, Shane A.; Blazquez, Pablo M.

    2018-01-01

    The oculomotor system is the motor system of choice for many neuroscientists studying motor control and learning because of its simplicity, easy control of inputs (e.g., visual stimulation), and precise control and measurement of motor outputs (eye position). This is especially true in primates, which are easily trained to perform oculomotor tasks. Here we provide the first detailed characterization of the oculomotor performance of trained squirrel monkeys, primates used extensively in oculomotor physiology, during saccade and smooth pursuit tasks, and compare it to that of the rhesus macaque. We found that both primates have similar oculomotor behavior but the rhesus shows a larger oculomotor range, better performance for horizontal saccades above 10 degrees, and better horizontal smooth pursuit gain to target velocities above 15 deg/s. These results are important for interspecies comparisons and necessary when selecting the best stimuli to study motor control and motor learning in the oculomotor systems of these primates. PMID:21656216

  15. Real-time Bioluminescence Imaging of Macroencapsulated Fibroblasts Reveals Allograft Protection in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Tarantal, Alice F.; Lee, C. Chang I.; Itkin-Ansari, Pamela

    2009-01-01

    Background Encapsulation of cells has the potential to eliminate the need for immunosuppression for cellular transplantation. Recently, the TheraCyte® device was shown to provide long-term immunoprotection of murine islets in the NOD/SCID mouse model of diabetes. In this report, translational studies were undertaken using skin fibroblasts from an unrelated rhesus monkey donor that were transduced with an HIV-1-derived lentiviral vector expressing firefly luciferase permitting the use of bioluminescence imaging (BLI) to monitor cell survival over time and in a noninvasive manner. Methods Encapsulated cells were transplanted subcutaneously (N=2) or cells were injected without encapsulation (N=1) and outcomes compared. BLI was performed to monitor cell survival. Results The BLI signal from the encapsulated cells remained robust post-insertion, and in one animal persisted for up to 1 year. In contrast, the control animal that received unencapsulated cells exhibited a complete loss of cell signal within 14 days. Conclusions These data demonstrate that TheraCyte® encapsulation of allogeneic cells provides robust immune protection in transplanted rhesus monkeys. PMID:19584678

  16. Mitigation of septic shock in mice and rhesus monkeys by human chorionic gonadotrophin-related oligopeptides

    PubMed Central

    Khan, N A; Vierboom, M P M; van Holten – Neelen, C; Breedveld, E; Zuiderwijk-Sick, E; Khan, A; Kondova, I; Braskamp, G; Savelkoul, H F J; Dik, W A; ‘t Hart, B A; Benner, R

    2010-01-01

    The marked improvement of several immune-mediated inflammatory diseases during pregnancy has drawn attention to pregnancy hormones as potential therapeutics for such disorders. Low molecular weight fractions derived from the pregnancy hormone human chorionic gonadotrophin (hCG) have remarkable potent immunosuppressive effects in mouse models of diabetes and septic shock. Based on these data we have designed a set of oligopeptides related to the primary structure of hCG and tested these in models of septic shock in mice and rhesus monkeys. We demonstrate that mice exposed to lipopolysaccharide (LPS) and treated subsequently with selected tri-, tetra-, penta- and hepta-meric oligopeptides (i.e. MTR, VVC, MTRV, LQGV, AQGV, VLPALP, VLPALPQ) are protected against fatal LPS-induced septic shock. Moreover, administration of a cocktail of three selected oligopeptides (LQGV, AQGV and VLPALP) improved the pathological features markedly and nearly improved haemodynamic parameters associated with intravenous Escherichia coli-induced septic shock in rhesus monkeys. These data indicate that the designed hCG-related oligopeptides may present a potential treatment for the initial hyperdynamic phase of septic shock in humans. PMID:20345979

  17. Challenges to maternal wellbeing during pregnancy impact temperament, attention, and neuromotor responses in the infant rhesus monkey.

    PubMed

    Coe, Christopher L; Lubach, Gabriele R; Crispen, Heather R; Shirtcliff, Elizabeth A; Schneider, Mary L

    2010-11-01

    The relative maturity, alertness, and reactivity of an infant at birth are sensitive indices of the neonate's health, the quality of the pregnancy, and the mother's wellbeing. Even when fetal growth and gestation length have been normal, the maturing fetus can still be adversely impacted by both physical events and psychological challenges to the mother during the prenatal period. The following research evaluated 413 rhesus monkeys from 7 different types of pregnancies to determine which conditions significantly influenced the behavioral responsiveness and state of the young infant. A standardized test battery modeled after the Neonatal Behavioral Assessment Scale for human newborns was employed. The largest impairments in orientation and increases in infant emotional reactivity were seen when female monkeys drank alcohol, even though consumed at only moderate levels during part of the pregnancy. The infants' ability to focus and attend to visual and auditory cues was also affected when the gravid female's adrenal hormones were transiently elevated for 2 weeks by ACTH administration. In addition, responses to tactile and vestibular stimulation were altered by both this ACTH treatment and psychological disturbance during gestation. Conversely, a 2-day course of antenatal corticosteroids 1 month before term resulted in infants with lower motor activity and reactivity. These findings highlight several pregnancy conditions that can affect a young infant's neurobehavioral status, even when otherwise healthy, and demonstrate that alterations or deficits are specific to the type of insult experienced by the mother and fetus. © 2010 Wiley Periodicals, Inc.

  18. Causal prophylactic efficacy of primaquine, tafenoquine, and atovaquone-proguanil against Plasmodium cynomolgi in a rhesus monkey model.

    PubMed

    DiTusa, Charles; Kozar, Michael P; Pybus, Brandon; Sousa, Jason; Berman, Jonathan; Gettayacamin, Montip; Im-erbsin, Rawiwan; Tungtaeng, Anchalee; Ohrt, Colin

    2014-10-01

    Since the 1940s, the large animal model to assess novel causal prophylactic antimalarial agents has been the Plasmodium cynomolgi sporozoite-infected Indian-origin rhesus monkey. In 2009 the model was reassessed with 3 clinical standards: primaquine (PQ), tafenoquine (TQ), and atovaquone-proguanil. Both control monkeys were parasitemic on day 8 post-sporozoite inoculation on day 0. Primaquine at 1.78 mg base/kg/day on days (-1) to 8 protected 1 monkey and delayed parasitemia patency of the other monkey to day 49. Tafenoquine at 6 mg base/kg/day on days (-1) to 1 protected both monkeys. However, atovaquone-proguanil at 10 mg atovaquone/kg/day on days (-1) to 8 did not protect either monkey and delayed patency only to days 18-19. Primaquine and TQ at the employed regimens are proposed as appropriate doses of positive control drugs for the model at present.

  19. Effects of short-term oral dosing of polychlorotrifluoroethylene (polyCTFE) on the rhesus monkey.

    PubMed

    Jones, C E; Ballinger, M B; Mattie, D R; DelRaso, N J; Seckel, C; Vinegar, A

    1991-02-01

    Polychlorotrifluoroethylene (polyCTFE--primarily oligomers with 3-4 monomer units), a non-flammable hydraulic fluid for aircraft, was given daily for 15 days by oral gavage to four Rhesus monkeys at a concentration of 0.725 g kg-1. The administered dose was at a level that had caused toxicity in rats. Steady-state blood and liver concentrations reached were the same in both species. In monkeys, polyCTFE did not cause the electrolyte, serum protein, liver enzyme and anemic disturbances previously seen in rats. Liver sections taken at 15 days, analyzed for palmitoyl Co-A beta-oxidation rates or by electron microscopy, showed no significant indication of peroxisomal proliferation. An increased blood urea nitrogen (BUN) at 15 days was the only clinical pathological abnormality seen in both monkeys and rats. Previously unobserved effects were increased triglycerides and glycogen depletion.

  20. Intermittent convection-enhanced delivery of GDNF into rhesus monkey putamen: absence of local or cerebellar toxicity.

    PubMed

    Luz, Matthias; Allen, Philip C; Bringas, John; Boiko, Chris; Stockinger, Diane E; Nikula, Kristen J; Lewis, Owen; Woolley, Max; Fibiger, H Christian; Bankiewicz, Krystof; Mohr, Erich

    2018-05-22

    Glial cell line-derived neurotrophic factor (GDNF) has demonstrated neurorestorative and neuroprotective effects in rodent and nonhuman primate models of Parkinson's disease. However, continuous intraputamenal infusion of GDNF (100 µg/day) resulted in multifocal cerebellar Purkinje cell loss in a 6-month toxicity study in rhesus monkeys. It was hypothesized that continuous leakage of GDNF into the cerebrospinal fluid compartment during the infusions led to down-regulation of GDNF receptors on Purkinje cells, and that subsequent acute withdrawal of GDNF then mediated the observed cerebellar lesions. Here we present the results of a 9-month toxicity study in which rhesus monkeys received intermittent intraputamenal infusions via convection-enhanced delivery. Animals were treated with GDNF (87.1 µg; N = 14) or vehicle (N = 6) once every 4 weeks for a total of 40 weeks (11 treatments). Four of the GDNF-treated animals were utilized in a satellite study assessing the impact of concomitant catheter repositioning prior to treatment. In the main study, eight animals (5 GDNF, 3 control) were euthanized at the end of the treatment period, along with the four satellite study animals, while the remaining eight animals (5 GDNF, 3 control) were euthanized at the end of a 12-week recovery period. There were no GDNF-related adverse effects and in particular, no GDNF-related microscopic findings in the brain, spinal cord, dorsal root ganglia, or trigeminal ganglia. Therefore, 87.1 µg/4 weeks is considered the no observed adverse effect level for GDNF in rhesus monkeys receiving intermittent, convection-enhanced delivery of GDNF for 9 months.

  1. Therapeutic Efficacy of the Small Molecule GS-5734 against Ebola virus in Rhesus Monkeys

    DTIC Science & Technology

    2016-03-02

    distribution to sanctuary sites for viral 46 replication including testes, eye , and brain. In a rhesus monkey model of EVD, once daily 47...including respiratory syncytial virus (RSV), Junin virus (JUNV), Lassa fever virus 121 (LASV) and Middle East respiratory syndrome virus (MERS), with...yellow fever virus, dengue virus type 2), parainfluenza type 3, and severe 124 acute respiratory syndrome (SARS) associated coronavirus but little or

  2. Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.

    PubMed

    Wu, XuJun; Zhao, Ning; Bai, Fan; Li, ChuanYu; Liu, CiRong; Wei, JingKuan; Zong, Wei; Yang, LiXin; Ryabinin, Andrey E; Ma, YuanYe; Wang, JianHong

    2016-05-01

    Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction

  3. Elastic properties of external cortical bone in the craniofacial skeleton of the rhesus monkey.

    PubMed

    Wang, Qian; Dechow, Paul C

    2006-11-01

    Knowledge of elastic properties and of their variation in the cortical bone of the craniofacial skeleton is indispensable for creating accurate finite-element models to explore the biomechanics and adaptation of the skull in primates. In this study, we measured elastic properties of the external cortex of the rhesus monkey craniofacial skeleton, using an ultrasonic technique. Twenty-eight cylindrical cortical specimens were removed from each of six craniofacial skeletons of adult Macaca mulatta. Thickness, density, and a set of longitudinal and transverse ultrasonic velocities were measured on each specimen to allow calculation of the elastic properties in three dimensions, according to equations derived from Newton's second law and Hooke's law. The axes of maximum stiffness were determined by fitting longitudinal velocities measured along the perimeter of each cortical specimen to a sinusoidal function. Results showed significant differences in elastic properties between different functional areas of the rhesus cranium, and that many sites have a consistent orientation of maximum stiffness among specimens. Overall, the cortical bones of the rhesus monkey skull can be modeled as orthotropic in many regions, and as transversely isotropic in some regions, e.g., the supraorbital region. There are differences from human crania, suggesting that structural differences in skeletal form relate to differences in cortical material properties across species. These differences also suggest that we require more comparative data on elastic properties in primate craniofacial skeletons to explore effectively the functional significance of these differences, especially when these differences are elucidated through modeling approaches, such as finite-element modeling. (c) 2006 Wiley-Liss, Inc.

  4. Calorie restriction in rhesus monkeys.

    PubMed

    Mattison, Julie A; Lane, Mark A; Roth, George S; Ingram, Donald K

    2003-01-01

    Calorie restriction (CR) extends lifespan and reduces the incidence and age of onset of age-related disease in several animal models. To determine if this nutritional intervention has similar actions in a long-lived primate species, the National Institute on Aging (NIA) initiated a study in 1987 to investigate the effects of a 30% CR in male and female rhesus macaques (Macaca mulatta) of a broad age range. We have observed physiological effects of CR that parallel rodent studies and may be predictive of an increased lifespan. Specifically, results from the NIA study have demonstrated that CR decreases body weight and fat mass, improves glucoregulatory function, decreases blood pressure and blood lipids, and decreases body temperature. Juvenile males exhibited delayed skeletal and sexual maturation. Adult bone mass was not affected by CR in females nor were several reproductive hormones or menstrual cycling. CR attenuated the age-associated decline in both dehydroepiandrosterone (DHEA) and melatonin in males. Although 81% of the monkeys in the study are still alive, preliminary evidence suggests that CR will have beneficial effects on morbidity and mortality. We are now preparing a battery of measures to provide a thorough and relevant analysis of the effectiveness of CR at delaying the onset of age-related disease and maintaining function later into life.

  5. Social subordination produces distinct stress-related phenotypes in female rhesus monkeys

    PubMed Central

    Michopoulos, Vasiliki; Higgins, Melinda; Toufexis, Donna; Wilson, Mark E

    2012-01-01

    Social subordination in female macaques is imposed by harassment and the threat of aggression and produces reduced control over one's social and physical environment and a dysregulation of the limbic-hypothalamic-pituitary-adrenal axis resembling that observed in people suffering from psychopathologies. These effects support the contention that this particular animal model is an ethologically relevant paradigm in which to investigate the etiology of stress-induced psychological illness related to women. Here, we sought to expand this model by performing a discriminate analysis (DA) on 33 variables within three domains; behavioral, metabolic/anthropomorphic, and neuroendocrine, collected from socially housed female rhesus monkeys in order to assess whether exposure to social subordination produces a distinct phenotype. A receiver operating characteristic (ROC) curve was also calculated to determine each domain's classification accuracy. DA found significant markers within each domain that differentiated dominant and subordinate females. Subordinate females received more aggression, showed more submissive behavior, and received less of affiliation from others than did dominant females. Metabolic differences included increased leptin, and reduced adiponectin in dominant compared to subordinate females. Dominant females exhibited increased sensitivity to hormonal stimulation with higher serum LH in response to estradiol, cortisol in response to ACTH, and increased glucocorticoid negative feedback. Serum oxytocin, CSF DOPAC and serum PACAP were all significantly higher in dominant females. ROC curve analysis accurately predicted social status in all three domains. Results suggest that socially house rhesus monkeys represent a cogent animal model in which to study the physiology and behavioral consequences of chronic psychosocial stress in humans. PMID:22244748

  6. A 75-Year Pictorial History of the Cayo Santiago Rhesus Monkey Colony

    PubMed Central

    KESSLER, MATTHEW J.; RAWLINS, RICHARD G.

    2015-01-01

    This article presents a pictorial history of the free-ranging colony of rhesus monkeys (Macaca mulatta) on Cayo Santiago, Puerto Rico, in commemoration of the 75th anniversary of its establishment by Clarence R. Carpenter in December 1938. It is based on a presentation made by the authors at the symposium, Cayo Santiago: 75 Years of Leadership in Translational Research, held at the 36th Annual Meeting of the American Society of Primatologists in San Juan, Puerto Rico, on 20 June 2013. PMID:25764995

  7. Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey.

    PubMed

    Weininger, J; King, J C

    1982-06-01

    Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.

  8. Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Hill, F. S.; Cox, A. B.; Salmon, Y. L.; Cantu, A. O.; Lucas, J. N.

    1994-01-01

    The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.

  9. Mu/Kappa Opioid Interactions in Rhesus Monkeys: Implications for Analgesia and Abuse Liability

    PubMed Central

    Negus, S. Stevens; Katrina Schrode, KA; Stevenson, Glenn W.

    2008-01-01

    Mu opioid receptor agonists are clinically valuable as analgesics; however, their use is limited by high abuse liability. Kappa opioid agonists also produce antinociception, but they do not produce mu agonist-like abuse-related effects, suggesting that they may enhance the antinociceptive effects and/or attenuate the abuse-related effects of mu agonists. To evaluate this hypothesis, the present study examined interactions between the mu agonist fentanyl and the kappa agonist U69,593 in three behavioral assays in rhesus monkeys. In an assay of schedule-controlled responding, monkeys responded under a fixed-ratio 30 (FR 30) schedule of food presentation. Fentanyl and U69,593 each produced rate-decreasing effects when administered alone, and mixtures of 0.22:1, 0.65:1 and 1.96:1 U69,593/fentanyl usually produced subadditive effects. In an assay of thermal nociception, tail withdrawal latencies were measured from water heated to 50°C. Fentanyl and U69,593 each produced dose-dependent antinociception, and effects were additive for all mixtures. In an assay of drug self-administration, rhesus monkeys responded for i.v. drug injection, and both dose and FR values were manipulated. Fentanyl maintained self-administration, whereas U69,593 did not. Addition of U69,593 to fentanyl produced a proportion-dependent decrease in both rates of fentanyl self-administration and behavioral economic measures of the reinforcing efficacy of fentanyl. Taken together, these results suggest that simultaneous activation of mu and kappa receptors, either with a mixture of selective drugs or with a single drug that targets both receptors, may reduce abuse liability without reducing analgesic effects relative to selective mu agonists administered alone. PMID:18837635

  10. Comparison between carbachol iontophoresis and intravenous pilocarpine stimulated accommodation in anesthetized rhesus monkeys.

    PubMed

    Wendt, Mark; He, Lin; Glasser, Adrian

    2013-10-01

    Rhesus monkeys are an animal model for human accommodation and presbyopia and consistent and repeatable methods are needed to stimulate and measure accommodation in anesthetized rhesus monkeys. Accommodation has typically been pharmacologically stimulated with topical pilocarpine or carbachol iontophoresis. Intravenous (i.v.) pilocarpine has recently been shown to produce more natural, rapid and reproducible accommodative responses compared to topical pilocarpine. Here, i.v. pilocarpine was compared to carbachol iontophoresis stimulated accommodation. Experiments were performed under anaesthesia on five previously iridectomized monkeys aged 10-16 years. In three monkeys, accommodation was stimulated with carbachol iontophoresis in five successive experiments and refraction measured with a Hartinger coincidence refractometer. In separate experiments, accommodation was stimulated using a 5 mg/kg bolus of i.v. pilocarpine given over 30 s followed by a continuous infusion of 20 mg/kg/hr for 5.5 min in three successive experiments with the same monkeys as well as in single experiments with two additional monkeys. Refraction was measured continuously using photorefraction with baseline and accommodated refraction also measured with the Hartinger. In subsequent i.v. pilocarpine experiments with each monkey, accommodative changes in lens equatorial diameter were measured in real-time with video-image analysis. Maximum accommodation of three monkeys with carbachol iontophoresis (five repeats) was (mean ± SD; range) 14.0 ± 3.5; 9.9-20.3 D and with i.v. pilocarpine stimulation (three repeats) was 11.1 ± 1.1; 9.9-13.0 D. The average of the standard deviations of maximum accommodation from each monkey was 0.8 ± 0.3 D from carbachol iontophoresis and 0.3 ± 0.2 from i.v. pilocarpine. The average latency to the start of the response after carbachol iontophoresis was 2.5 ± 3.9; 0.0-12.0 min with a time constant of 12.7 ± 9.5; 2.3-29.2 min. The average

  11. Homogeneous immunoglobulins in sera of Rhesus monkeys after lethal irradiation and bone marrow transplantation

    PubMed Central

    Rádl, J.; van den Berg, P.; Voormolen, M.; Hendriks, W. D. H.; Schaefer, U. W.

    1974-01-01

    The immunoglobulin pattern in the sera of lethally irradiated and bone marrow transplanted Rhesus monkeys was studied during the reconstitution of their immune system. All of the irradiated monkeys which survived longer than 30 days, and in which reconstitution of their immune system took place, also developed homogeneous immunoglobulins (HI) in their sera. These homogeneous, sometimes multiple, immunoglobulins were transient. However, they persisted frequently in the sera for several months. In two monkeys which were additionally immunized with a complex antigen (normal human serum), clear-cut M-components appeared in the serum about 10 days later. These HI of IgG class did not precipitate the antigen in immunodiffusion techniques; however, when passing the serum through an immunoadsorbent prepared from normal human serum, only the HI were specifically retained on the column and afterwards isolated by elution. ImagesFIG. 1FIG. 2 PMID:4143277

  12. Blood schizontocidal activity of WR 238605 (Tafenoquine) against Plasmodium cynomolgi and Plasmodium fragile infections in rhesus monkeys.

    PubMed

    Puri, S K; Dutta, G P

    2003-04-01

    A new 8-aminoquinoline antimalarial WR 238605 (Tafenoquine), developed initially as a primaquine alternative for prevention of Plasmodium vivax relapses was evaluated for blood schizontocidal activity against two simian malaria infections namely Plasmodium cynomolgi B and Plasmodium fragile in rhesus monkeys. Treatment with WR 238605 at a dose of 3.16 mg(base)/kg/day x 7 days cured established trophozoite induced infections in monkeys with both these parasites. The lower dose of 1.00 mg/kg/day cured 9 out of 12 monkeys infected with P. cynomolgi B and 10 out of 11 monkeys infected with P. fragile. Primaquine was only partially curative at 10.0 mg(base)/kg/day x 7 dose regimen against both these infections. The potent blood schizontocidal activity of tafenoquine adds to the armoury of antimalarial drugs.

  13. Comparative Metabolism Study of Five Protoberberine Alkaloids in Liver Microsomes from Rat, Rhesus Monkey, and Human.

    PubMed

    Li, Yan; Zhou, Yanyan; Si, Nan; Han, Lingyu; Ren, Wei; Xin, Shaokun; Wang, Hongjie; Zuo, Ran; Wei, Xiaolu; Yang, Jian; Zhao, Haiyu; Bian, Baolin

    2017-11-01

    Protoberberine alkaloids including berberine, palmatine, jatrorrhizine, coptisine, and epiberberine are major components in many medicinal plants. They have been widely used for the treatment of cancer, inflammation, diabetes, depression, hypertension, and various infectious areas. However, the metabolism of five protoberberine alkaloids among different species has not been clarified previously. In order to elaborate on the in vitro metabolism of them, a comparative analysis of their metabolic profile in rat, rhesus monkey, and human liver microsomes was carried out using ultrahigh-performance liquid chromatography coupled with a high-resolution linear trap quadrupole-Orbitrap mass spectrometer (UHPLC-electrospray ionization-Orbitrap MS) for the first time. Each metabolite was identified and semiquantified by its accurate mass data and peak area. Fifteen metabolites were characterized based on accurate MS/MS spectra and the proposed MS/MS fragmentation pathways including demethylation, hydroxylation, and methyl reduction. Among them, the content of berberine metabolites in human liver microsomes was similar with those in rhesus monkey liver microsomes, whereas berberine in rat liver microsomes showed no demethylation metabolites and the content of metabolites showed significant differences with that in human liver microsomes. On the contrary, the metabolism of palmatine in rat liver microsomes resembled that in human liver microsomes. The content of jatrorrhizine metabolites presented obvious differences in all species. The HR-ESI-MS/MS fragmentation behavior of protoberberine alkaloids and their metabolic profile in rat, rhesus monkey, and human liver microsomes were investigated for the first time. The results demonstrated that the biotransformation characteristics of protoberberine alkaloids among different species had similarities as well differences that would be beneficial for us to better understand the pharmacological activities of protoberberine alkaloids

  14. Effect of rotopositioning on the growth and maturation of mandibular bone in immobilized Rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Simmons, D. J.; Parvin, C.; Smith, K. C.; France, P.; Kazarian, L.

    1986-01-01

    The rates of bone formation and mineralization in the mandibular cortex of juvenile Rhesus monkeys exposed to immobilization/rotopositioning are evaluated. The monkeys were restrained in a supine position and rotated 90 deg every 30 minutes through a full 360 deg for 14 days. The microscopic distribution of mineral densities in osteonal bone and the porosity of cortical bone are studied using microradiographs, and osteon closure rates are assessed using tetracycline labeling; normal distributions of osteons of different mineral density and cortical bone porosity values are observed. It is concluded that 14 days of immobilization/rotopositioning did not cause abnormal changes in osteon mineralization, cortical porosity, and osteon closure rates.

  15. Hypocretin/orexin antagonists decrease cocaine self-administration by female rhesus monkeys.

    PubMed

    Foltin, Richard W; Evans, Suzette M

    2018-07-01

    The hypocretin/orexin system is involved in regulating arousal, and much recent work demonstrates that decreasing hypocretin receptor-1 (HCRTr1) activity using antagonists decreases appetitive behavior, including stimulant drug self-administration and reinstatement. The present study determined the effects of hypocretin-1 and HCRTr1 antagonists on responding reinforced by intravenous (i.v.) cocaine self-administration (0.0125 - 0.05 mg/kg/infusion) in 5 female rhesus monkeys. Responding was examined using 3 schedules of reinforcement: 1) a Fixed interval 1 min, Fixed ratio 10 Chain schedule [FI 1-min (FR10:S)], 2) a Progressive Ratio (PR) schedule, and 3) a cocaine vs. candy. Choice schedule: the HCRTr1 antagonist SB-334867 (8-24 mg/kg, i.m.) decreased cocaine taking under the Chain schedule and PR schedule in all 5 monkeys and in 4 of the 5 monkeys under the Choice schedule. d- Amphetamine (0.06 - 0.25 mg/kg, i.m.), tested as a control manipulation, decreased cocaine taking in all 5 monkeys under the Chain schedule. The peptide hypocretin-1 (0.072 mg/kg, i.v.) increased cocaine taking in the monkeys with low rates of cocaine taking under the Chain (3/4) and Choice (4/5) schedules. Reinstatement of extinguished cocaine responding following response-independent delivery of a large dose of cocaine (0.3 mg/kg) was attenuated in 3 of the 5 monkeys by the HCRTr1 antagonist SB-334867. These data expand upon work accomplished in predominantly male rodents suggesting that the hypocretin system modulates the response to appetitive stimuli. A better understanding of this system offers promise as a novel approach in medication development for appetitive disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. The relationship between refractive and biometric changes during Edinger–Westphal stimulated accommodation in rhesus monkeys

    PubMed Central

    Vilupuru, Abhiram S.; Glasser, Adrian

    2010-01-01

    Experiments were undertaken to understand the relationship between dynamic accommodative refractive and biometric (lens thickness (LT), anterior chamber depth (ACD) and anterior segment length (ASL=ACD+LT)) changes during Edinger–Westphal stimulated accommodation in rhesus monkeys. Experiments were conducted on three rhesus monkeys (aged 11·5, 4·75 and 4·75 years) which had undergone prior, bilateral, complete iridectomies and implantation of a stimulating electrode in the Edinger–Westphal (EW) nucleus. Accommodative refractive responses were first measured dynamically with video-based infrared photorefraction and then ocular biometric responses were measured dynamically with continuous ultrasound biometry (CUB) during EW stimulation. The same stimulus amplitudes were used for the refractive and biometric measurements to allow them to be compared. Main sequence relationships (ratio of peak velocity to amplitude) were calculated. Dynamic accommodative refractive changes are linearly correlated with the biometric changes and accommodative biometric changes in ACD, ASL and LT show systematic linear correlations with increasing accommodative amplitudes. The relationships are relatively similar for the eyes of the different monkeys. Dynamic analysis showed that main sequence relationships for both biometry and refraction are linear. Although accommodative refractive changes in the eye occur primarily due to changes in lens surface curvature, the refractive changes are well correlated with A-scan measured accommodative biometric changes. Accommodative changes in ACD, LT and ASL are all well correlated over the full extent of the accommodative response. PMID:15721617

  17. Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?

    PubMed

    Fantegrossi, William E

    2007-01-01

    Many animal models relevant to the persistent effects of drugs of abuse necessitate the application of interspecies dose scaling procedures to approximate drug administration regimens in humans, but drug self-administration procedures differ in that they allow animal subjects to control their own drug intake. This report reviews the reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA), its enantiomers, and several structural analogs in rhesus monkeys, paying particular attention to the pharmacological mechanisms of such reinforcing effects, the development of structure activity relationships among these compounds, the stability of MDMA self-administration behavior over time, and the persistent effects of self-administered MDMA on monoamines. The methylenedioxy amphetamine congeners MDMA, 3,4-methylenedioxyamphetamine, N-ethyl-3,4-methylenedioxyamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine function as reinforcers in rhesus monkeys, maintaining self-administration behavior greater than that engendered by contingent saline but less than that engendered by traditional psychostimulants. These findings are remarkable as structurally distinct serotonergic hallucinogen-like drugs do not maintain reliable self-administration in laboratory animals. During prolonged MDMA self-administration, MDMA-maintained responding progressively weakens, and MDMA eventually fails to maintain significant self-administration. The neurochemical correlates of this effect have not yet been identified. Procedures in which MDMA and related compounds are self-administered can be established in rhesus monkeys. These techniques can be used to engender contingent MDMA exposure without resorting to controversial methods of interspecies dose scaling. As such, further application of self-administration methods may provide important new insights into the persistent effects of MDMA on brain and behavior in nonhuman primates.

  18. Impaired performance from brief social isolation of rhesus monkeys (Macaca mulatta) - A multiple video-task assessment

    NASA Technical Reports Server (NTRS)

    Washburn, David A.; Rumbaugh, Duane M.

    1991-01-01

    Social isolation has been demonstrated to produce profound and lasting psychological effects in young primates. In the present investigation, two adult rhesus monkeys (Macaca mulatta) were isolated from one another for up to 6 days and tested on 7 video tasks designed to assess psychomotor and cognitive functioning. Both the number and quality (i.e., speed and accuracy) of responses were significantly compromised in the social isolation condition relative to levels in which the animals were tested together. It is argued that adult rhesus are susceptible to performance disruption by even relatively brief social isolation, and that these effects can best be assessed by a battery of complex and sensitive measures.

  19. Recognition errors suggest fast familiarity and slow recollection in rhesus monkeys

    PubMed Central

    Basile, Benjamin M.; Hampton, Robert R.

    2013-01-01

    One influential model of recognition posits two underlying memory processes: recollection, which is detailed but relatively slow, and familiarity, which is quick but lacks detail. Most of the evidence for this dual-process model in nonhumans has come from analyses of receiver operating characteristic (ROC) curves in rats, but whether ROC analyses can demonstrate dual processes has been repeatedly challenged. Here, we present independent converging evidence for the dual-process model from analyses of recognition errors made by rhesus monkeys. Recognition choices were made in three different ways depending on processing duration. Short-latency errors were disproportionately false alarms to familiar lures, suggesting control by familiarity. Medium-latency responses were less likely to be false alarms and were more accurate, suggesting onset of a recollective process that could correctly reject familiar lures. Long-latency responses were guesses. A response deadline increased false alarms, suggesting that limiting processing time weakened the contribution of recollection and strengthened the contribution of familiarity. Together, these findings suggest fast familiarity and slow recollection in monkeys, that monkeys use a “recollect to reject” strategy to countermand false familiarity, and that primate recognition performance is well-characterized by a dual-process model consisting of recollection and familiarity. PMID:23864646

  20. Differential Antagonism of Cocaine Self-Administration and Cocaine-Induced Disruptions of Learning by Haloperidol in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Winsauer, Peter J.; Moerschbaecher, Joseph M.; Roussell, Alison M.

    2008-01-01

    Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032 - 0.032 mg/kg/infusion of cocaine increased response…

  1. Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations

    PubMed Central

    Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

    2014-01-01

    Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 108, 2 × 109 and 2 × 1010 colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 109 CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 1010 CFU). The challenge dose, 2 × 1010 CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. PMID:24028276

  2. Pit-1/growth hormone factor 1 splice variant expression in the rhesus monkey pituitary gland and the rhesus and human placenta.

    PubMed

    Schanke, J T; Conwell, C M; Durning, M; Fisher, J M; Golos, T G

    1997-03-01

    We have examined the expression of Pit-1 messenger RNA (mRNA) splice variants in the nonhuman primate pituitary and in rhesus and human placenta. Full-length complementary DNAs (cDNAs) representing Pit-1 and the Pit-1 beta splice variants were cloned from a rhesus monkey pituitary cDNA library and were readily detectable by RT-PCR with rhesus pituitary gland RNA. The Pit-1T variant previously reported in mouse pituitary tumor cell lines was not detectable in normal rhesus pituitary tissue, although two novel splice variants were detected. A cDNA approximating the rat Pit-1 delta 4 variant was cloned but coded for a truncated and presumably nonfunctional protein. Only by using a nested RT-PCR approach were Pit-1 and Pit-1 beta variants consistently detectable in both human and rhesus placental tissue. The Pit-1 beta variant mRNA was not detectable in JEG-3 choriocarcinoma cells unless the cells were stimulated with 8-Br-cAMP. Immunoblot studies with nuclear extracts from primary rhesus syncytiotrophoblast cultures or JEG-3 choriocarcinoma cells indicated that although mRNA levels were very low, Pit-1 protein was detectable in differentiated cytotrophoblasts, and levels increased after treatment with 8-Br-cAMP. Two major species of Pit-1 protein were detected that corresponded to the two major bands in rat pituitary GH3 cell nuclear extracts. Low levels of slightly larger bands also were seen, which may represent Pit-1 beta protein or phosphorylated species. We conclude that Pit-1 splice variants expressed in the primate pituitary gland differ from those in the rodent gland and that the Pit-1 and Pit-1 beta mRNAs expressed in the placenta give rise to a pattern of protein expression similar to that seen in pituitary cells, which is inducible by treatment with 8-Br-cAMP.

  3. Eruption of Permanent Dentition in Rhesus Monkeys Exposed to ELF (extremely Low Frequency) Fields.

    DTIC Science & Technology

    1983-04-01

    Medical Research and Development Commaiid M0096.001-1022 Reviewed by: Approved and Released by: Ashton Graybiel, M.D. Captain W. M. Houk , MC, USN...Chief Scientific Advisor Commanding Officer April 1983 NAVAL AEROSPACE MEDICAL RESEARCH LABORATORY NAVAL AIR S rATION PENSACOLA, FLuRIDA 32508 ii L ½.-- 1...significance level of .05, the calculated a E is .001. 2 V ! -A----;--! PROCEDURE Sixty rhesus monkeys (Macaca mulatta) were introduced into the ELF

  4. Therapeutic and protective efficacy of a dengue antibody against Zika infection in rhesus monkeys.

    PubMed

    Abbink, Peter; Larocca, Rafael A; Dejnirattisai, Wanwisa; Peterson, Rebecca; Nkolola, Joseph P; Borducchi, Erica N; Supasa, Piyada; Mongkolsapaya, Juthathip; Screaton, Gavin R; Barouch, Dan H

    2018-06-01

    Strategies to treat Zika virus (ZIKV) infection in dengue virus (DENV)-endemic areas are urgently needed. Here we show that a DENV-specific antibody against the E-dimer epitope (EDE) potently cross-neutralizes ZIKV and provides robust therapeutic efficacy as well as prophylactic efficacy against ZIKV in rhesus monkeys. Viral escape was not detected, suggesting a relatively high bar to escape. These data demonstrate the potential for antibody-based therapy and prevention of ZIKV.

  5. Pharmacokinetics of bisphenol A in neonatal and adult rhesus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Doerge, Daniel R., E-mail: daniel.doerge@fda.hhs.go; Twaddle, Nathan C.; Woodling, Kellie A.

    Bisphenol A (BPA) is a high-production volume industrial chemical used in the manufacture of polycarbonate plastic products and epoxy resin-based food can liners. The presence of BPA in urine of > 90% of Americans aged 6-60 is controversial because of the potential for endocrine disruption, particularly during perinatal development, as suggested by in vitro, experimental animal, and epidemiological studies. The current study used LC/MS/MS to measure serum pharmacokinetics of aglycone (active) and conjugated (inactive) BPA in adult and neonatal rhesus monkeys by oral (PND 5, 35, 70) and intravenous injection (PND 77) routes using d6-BPA to avoid sample contamination. Themore » concentration-time profiles observed in adult monkeys following oral administration of 100 {mu}g/kg bw were remarkably similar to those previously reported in human volunteers given a similar dose; moreover, minimal pharmacokinetic differences were observed between neonatal and adult monkeys for the receptor-active aglycone form of BPA. Circulating concentrations of BPA aglycone were quite low following oral administration (< 1% of total), which reflects the redundancy of active UDP-glucuronosyl transferase isoforms in both gut and liver. No age-related changes were seen in internal exposure metrics for aglycone BPA in monkeys, a result clearly different from developing rats where significant inverse age-related changes, based on immaturity of Phase II metabolism and renal excretion, were recently reported. These observations imply that any toxicological effect observed in rats from early postnatal exposures to BPA could over-predict those possible in primates of the same age, based on significantly higher internal exposures and overall immaturity at birth.« less

  6. Endovascular ischemic stroke models of adult rhesus monkeys: a comparison of two endovascular methods.

    PubMed

    Wu, Di; Chen, Jian; Wang, Bincheng; Zhang, Mo; Shi, Jingfei; Ma, Yanhui; Zhu, Zixin; Yan, Feng; He, Xiaoduo; Li, Shengli; Dornbos Iii, David; Ding, Yuchuan; Ji, Xunming

    2016-08-18

    To further investigate and improve upon current stroke models in nonhuman primates, infarct size, neurologic function and survival were evaluated in two endovascular ischemic models in sixteen rhesus monkeys. The first method utilized a micro-catheter or an inflatable balloon to occlude the M1 segment in six monkeys. In the second model, an autologous clot was injected via a micro-catheter into the M1 segment in ten monkeys. MRI scanning was performed on all monkeys both at baseline and 3 hours after the onset of ischemia. Spetzler neurologic functions were assessed post-operatively, and selective perfusion deficits were confirmed by DSA and MRI in all monkeys. Animals undergoing micro-catheter or balloon occlusion demonstrated more profound hemiparesis, larger infarct sizes, lower Spetzler neurologic scores and increased mortality compared to the thrombus occlusion group. In animals injected with the clot, there was no evidence of dissolution, and the thrombus was either near the injection site (M1) or flushed into the superior division of the MCA (M2). All animals survived the M2 occlusion. M1 occlusion with thrombus generated 50% mortality. This study highlighted clinically important differences in these two models, providing a platform for further study of a translational thromboembolic model of acute ischemic stroke.

  7. Lack of dose dependent kinetics of methyl salicylate-2-O-β-D-lactoside in rhesus monkeys after oral administration.

    PubMed

    He, Yangyang; Yan, Yu; Zhang, Tiantai; Ma, Yinzhong; Zhang, Wen; Wu, Ping; Song, Junke; Wang, Shuang; Du, Guanhua

    2015-04-22

    Methyl salicylate-2-O-β-d-lactoside (MSL) is one of the main active components isolated from Gaultheria yunnanensis, which is a traditional Chinese medicine used to treat arthritis and various aches and pains. Pharmacological researches showed that MSL had various effective activities in both in vivo and in vitro experiments. However, the pharmacokinetics features and oral bioavailability of MSL in primates were not studied up to now. To study the pharmacokinetics of different doses of MSL in rhesus monkeys and investigate the absolute bioavailability of MSL after oral administration. Male and female rhesus monkeys were either orally administrated with MSL 200, 400 and 800 mg/kg or received an intravenous dose of 20mg/kg randomly. The levels of MSL and salicylic acid (SA) in plasma were simultaneous measured by a simple, sensitive and reproducible high performance liquid chromatography method. Mean peak plasma concentration values for groups treated with 200, 400 and 800 mg/kg doses ranged from 48.79 to 171.83 μg/mL after single-dose oral administration of MSL, and mean area under the concentration-time curve values ranged from 195.16 to 1107.76 μg/mL h. Poor linearity of the kinetics of SA after oral administration of MSL was observed in the regression analysis of the Cmax-dose plot (r(2)=0.812), CL-dose plot (r(2)=0.225) and AUC(0-t)-dose plot (r(2)=0.938). Absolute bioavailability of MSL was assessed to be 118.89 ± 57.50, 213.54 ± 58.98 and 168.72 ± 76.58%, respectively. Bioavailability of MSL after oral administration in rhesus monkeys was measured for the first time. Pharmacokinetics parameters did not appear to be dose proportional among the three oral doses of treatments, and MSL showed an apparent absolute bioavailability in excess of 100% in rhesus monkeys based on the present study. In addition, a rapid, sensitive and reliable HPLC method was established and demonstrated for the research of traditional Chinese medicine in this study. Copyright

  8. Serological reactions in Rhesus monkeys inoculated with the 17D strain of yellow fever virus.

    PubMed

    GROOT, H

    1962-01-01

    Haemagglutination-inhibition tests, which depend on the appearance of haemagglutination-inhibiting antibodies in the serum in virus infections, are in common use in the study of arthropod-borne diseases. This paper contains the results of an investigation into the appearance and pattern of haemagglutination-inhibiting antibodies in the serum of rhesus monkeys inoculated intracerebrally with the 17D strain of yellow fever virus during the testing of seed lots of yellow fever vaccine. These antibodies appeared on the tenth day after inoculation, and were still demonstrable four years later. In all of the eight monkeys tested complement-fixing and neutralizing antibodies against yellow fever antigens also developed, and in six out of the eight heterologous antigens developed.

  9. Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys

    PubMed Central

    Abbott, David H; Tarantal, Alice F; Dumesic, Daniel A

    2010-01-01

    Old World monkeys provide naturally-occurring and experimentally-induced phenotypes closely resembling the highly prevalent polycystic ovary syndrome (PCOS) in women. In particular, experimentally-induced fetal androgen excess in female rhesus monkeys produces a comprehensive adult PCOS-like phenotype that includes both reproductive and metabolic dysfunction found in PCOS women. Such a reliable experimental approach enables the use of the prenatally androgenized (PA) female rhesus monkey model to (1) examine fetal, infant and adolescent antecedents of adult pathophysiology, gaining valuable insight into early phenotypic expression of PCOS, and (2) to understand adult pathophysiology from a mechanistic perspective. Elevated circulating luteinizing hormone (LH) levels are the earliest indication of reproductive dysfunction in late gestation nonhuman primate fetuses and infants exposed to androgen excess during early (late first to second trimester) gestation. Such early gestation-exposed PA infants also are hyperandrogenic, with both LH hypersecretion and hyperandrogenism persisting in early gestation-exposed PA adults. Similarly, subtle metabolic abnormalities appearing in young nonhuman primate infants and adolescents precede the abdominal adiposity, hyperliplidemia, and increased incidence of type 2 diabetes that characterize early gestated-exposed PA adults. These new insights into the developmental origins of PCOS, and progression of the pathophysiology from infancy to adulthood, provide opportunities for clinical intervention to ameliorate the PCOS phenotype thus providing a preventive health care approach to PCOS-related abnormalities. For example, PCOS-like traits in PA monkeys, as in PCOS women, can improve with better insulin-glucose homeostasis, suggesting that lifestyle interventions preventing increased adiposity in adolescent daughters of PCOS mothers also may reduce their risk of acquiring many PCOS-related metabolic abnormalities in adulthood. PMID

  10. Rhesus monkeys (Macaca mulatta), video tasks, and implications for stimulus-response spatial contiguity

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.; Richardson, W. Kirk; Washburn, David A.; Hopkins, William D.; Savage-Rumbaugh, E. Sue

    1989-01-01

    Recent reports support the argument that the efficiency of primate learning is compromised to the degree that there is spatial discontiguity between discriminands and the locus of response. Experiments are reported here in which two rhesus monkeys easily mastered precise control of a joystick to respond to a variety of computer-generated targets despite the fact that the joystick was located 9 to 18 cm from the video screen. It is argued that stimulus-response contiguity is a significant parameter of learning only to the degree that the monkey visually attends to the directional movements of its hand in order to displace discriminands. If attention is focused on the effects of the hand's movement rather than on the hand itself, stimulus-response contiguity is no longer a primary parameter of learning. The implications of these results for mirror-guided studies are discussed.

  11. Wild rhesus monkeys generate causal inferences about possible and impossible physical transformations in the absence of experience

    PubMed Central

    Hauser, Marc; Spaulding, Bailey

    2006-01-01

    Human infants and adults generate causal inferences about the physical world from observations of single, novel events, thereby violating Hume's thesis that spatiotemporal cooccurrence from prior experience drives causal perception in our species. Is this capacity unique or shared with other animals? We address this question by presenting the results of three experiments on free-ranging rhesus monkeys (Macaca mulatta), focusing specifically on their capacity to generate expectations about the nature of completely unfamiliar physical transformations. By using an expectancy violation looking-time method, each experiment presented subjects with either physically possible or impossible transformations of objects (e.g., a knife, as opposed to a glass of water, appears to cut an apple in half). In both experiments, subjects looked longer when the transformation was impossible than when it was possible. Follow up experiments ruled out that these patterns could be explained by association. These results show that in the absence of training or direct prior experience, rhesus monkeys generate causal inferences from single, novel events, using their knowledge of the physical world to guide such expectations. PMID:16641097

  12. Global gene expression analysis of peripheral blood mononuclear cells in rhesus monkey infants with CA16 infection-induced HFMD.

    PubMed

    Song, Jie; Hu, Yajie; Hu, Yunguang; Wang, Jingjing; Zhang, Xiaolong; Wang, Lichun; Guo, Lei; Wang, Yancui; Ning, Ruotong; Liao, Yun; Zhang, Ying; Zheng, Huiwen; Shi, Haijing; He, Zhanlong; Li, Qihan; Liu, Longding

    2016-03-02

    Coxsackievirus A16 (CA16) is a dominant pathogen that results in hand, foot, and mouth disease and causes outbreaks worldwide, particularly in the Asia-Pacific region. However, the underlying molecular mechanisms remain unclear. Our previous study has demonstrated that the basic CA16 pathogenic process was successfully mimicked in rhesus monkey infant. The present study focused on the global gene expression changes in peripheral blood mononuclear cells of rhesus monkey infants with hand, foot, and mouth disease induced by CA16 infection at different time points. Genome-wide expression analysis was performed with Agilent whole-genome microarrays and established bioinformatics tools. Nine hundred and forty-eight significant differentially expressed genes that were associated with 5 gene ontology categories, including cell communication, cell cycle, immune system process, regulation of transcription and metabolic process were identified. Subsequently, the mapping of genes related to the immune system process by PANTHER pathway analysis revealed the predominance of inflammation mediated by chemokine and cytokine signaling pathways and the interleukin signaling pathway. Ultimately, co-expressed genes and their networks were analyzed. The results revealed the gene expression profile of the immune system in response to CA16 in rhesus monkey infants and suggested that such an immune response was generated as a result of the positive mobilization of the immune system. This initial microarray study will provide insights into the molecular mechanism of CA16 infection and will facilitate the identification of biomarkers for the evaluation of vaccines against this virus. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Activation of the maternal immune system during pregnancy alters behavioral development of rhesus monkey offspring.

    PubMed

    Bauman, Melissa D; Iosif, Ana-Maria; Smith, Stephen E P; Bregere, Catherine; Amaral, David G; Patterson, Paul H

    2014-02-15

    Maternal infection during pregnancy is associated with an increased risk of schizophrenia and autism in the offspring. Supporting this correlation, experimentally activating the maternal immune system during pregnancy in rodents produces offspring with abnormal brain and behavioral development. We have developed a nonhuman primate model to bridge the gap between clinical populations and rodent models of maternal immune activation (MIA). A modified form of the viral mimic, synthetic double-stranded RNA (polyinosinic:polycytidylic acid stabilized with poly-L-lysine) was delivered to two separate groups of pregnant rhesus monkeys to induce MIA: 1) late first trimester MIA (n = 6), and 2) late second trimester MIA (n = 7). Control animals (n = 11) received saline injections at the same first or second trimester time points or were untreated. Sickness behavior, temperature, and cytokine profiles of the pregnant monkeys confirmed a strong inflammatory response to MIA. Behavioral development of the offspring was studied for 24 months. Following weaning at 6 months of age, MIA offspring exhibited abnormal responses to separation from their mothers. As the animals matured, MIA offspring displayed increased repetitive behaviors and decreased affiliative vocalizations. When evaluated with unfamiliar conspecifics, first trimester MIA offspring deviated from species-typical macaque social behavior by inappropriately approaching and remaining in immediate proximity of an unfamiliar animal. In this rhesus monkey model, MIA yields offspring with abnormal repetitive behaviors, communication, and social interactions. These results extended the findings in rodent MIA models to more human-like behaviors resembling those in both autism and schizophrenia. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  14. Do primates see the solitaire illusion differently? A comparative assessment of humans (Homo sapiens), chimpanzees (Pan troglodytes), rhesus monkeys (Macaca mulatta), and capuchin monkeys (Cebus apella).

    PubMed

    Agrillo, Christian; Parrish, Audrey E; Beran, Michael J

    2014-11-01

    An important question in comparative psychology is whether human and nonhuman animals share similar principles of perceptual organization. Despite much empirical research, no firm conclusion has been drawn. The Solitaire illusion is a numerosity illusion in humans that occurs when one misperceives the relative number of 2 types of items presented in intermingled sets. To date, no study has investigated whether nonhuman animals perceive the Solitaire illusion as humans do. Here, we compared the perception of the Solitaire illusion in human and nonhuman primates in 3 experiments. We first observed (Experiment 1) the spontaneous behavior of chimpanzees when presented with 2 arrays composed of a different number of preferred and nonpreferred food items. In probe trials, preferred items were presented in the Solitaire pattern in 2 different spatial arrangements (either clustered centrally or distributed on the perimeter). Chimpanzees did not show any misperception of quantity in the Solitaire pattern. Next, humans, chimpanzees, rhesus monkeys, and capuchin monkeys underwent the same testing of relative quantity judgments in a computerized task that also presented the Solitaire illusion (Experiments 2 and 3). Unlike humans, chimpanzees did not appear to perceive the illusion, in agreement with Experiment 1. The performance of rhesus monkeys and capuchin monkeys was also different from that of humans, but was slightly more indicative of a potential Solitaire illusion. On the whole, our results suggest a potential discontinuity in the visual mechanisms underlying the Solitaire illusion between human and nonhuman primates. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

  15. Evaluation of an intragastric challenge model for Shigella dysenteriae 1 in rhesus monkeys (Macaca mulatta) for the pre-clinical assessment of Shigella vaccine formulations.

    PubMed

    Islam, Dilara; Ruamsap, Nattaya; Khantapura, Patchariya; Aksomboon, Ajchara; Srijan, Apichai; Wongstitwilairoong, Boonchai; Bodhidatta, Ladaporn; Gettayacamin, Montip; Venkatesan, Malabi M; Mason, Carl J

    2014-06-01

    Shigellosis is a worldwide disease, characterized by abdominal pain, fever, vomiting, and the passage of blood- and mucus-streaked stools. Rhesus monkeys and other primates are the only animals that are naturally susceptible to shigellosis. A suitable animal model is required for the pre-clinical evaluation of vaccines candidates. In this study, the minimal dose of Shigella dysenteriae1 1617 strain required to produce dysentery in four of five (80% attack rate) monkeys using an escalating dose range for three groups [2 × 10(8) , 2 × 10(9) and 2 × 10(10) colony forming unit (CFU)] was determined. In addition, the monkeys were re-infected. The identified optimal challenge dose was 2 × 10(9) CFU; this dose elicited 60% protection in monkeys when they were re-challenged with a one log higher dose (2 × 10(10) CFU). The challenge dose, 2 × 10(10) CFU, produced severe dysentery in all monkeys, with one monkey dying within 24 h, elicited 100% protection when re-challenged with the same dose. All monkeys exhibited immune responses. This study concludes that the rhesus monkey model closely mimics the disease and immune response seen in humans and is a suitable animal model for the pre-clinical evaluation of Shigella vaccine candidates. Prior infection with the 1617 strain can protect monkeys against subsequent re-challenges with homologous strains. © 2013 The Authors. APMIS published by John Wiley & Sons Ltd.

  16. Simian hepatitis A virus derived from a captive rhesus monkey in India is similar to the strain isolated from wild African green monkeys in Kenya.

    PubMed

    Arankalle, V A; Ramakrishnan, J

    2009-03-01

    A simian hepatitis A virus (HAV) was identified retrospectively in a faecal sample from a rhesus monkey in India, inoculated in 1995 with a faecal suspension from a suspected patient of non-A to E hepatitis. The monkey was in captivity for 2 years in one of the experimental primate facilities in western India before being moved to the National Institute of Virology, Pune for experimentation. Phylogenetic analysis based on a partial sequence of the 5' noncoding region placed this virus in genotype V, the only other member being the AGM-27 strain recovered in 1986 from African green monkeys in Kenya. The source of infection of the monkey remains unclear. The full genome was amplified in nine fragments and sequenced. The genome of the Indian simian HAV (IND-SHAV) is 7425 nucleotides long including the poly-A tail of 14 nucleotides at the 3' end. At the nucleotide and amino acid levels, IND-SHAV was 99.8 and 100% identical with AGM27, respectively.

  17. Inferential Learning of Serial Order of Perceptual Categories by Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    2017-01-01

    Category learning in animals is typically trained explicitly, in most instances by varying the exemplars of a single category in a matching-to-sample task. Here, we show that male rhesus macaques can learn categories by a transitive inference paradigm in which novel exemplars of five categories were presented throughout training. Instead of requiring decisions about a constant set of repetitively presented stimuli, we studied the macaque's ability to determine the relative order of multiple exemplars of particular stimuli that were rarely repeated. Ordinal decisions generalized both to novel stimuli and, as a consequence, to novel pairings. Thus, we showed that rhesus monkeys could learn to categorize on the basis of implied ordinal position, without prior matching-to-sample training, and that they could then make inferences about category order. Our results challenge the plausibility of association models of category learning and broaden the scope of the transitive inference paradigm. SIGNIFICANCE STATEMENT The cognitive abilities of nonhuman animals are of enduring interest to scientists and the general public because they blur the dividing line between human and nonhuman intelligence. Categorization and sequence learning are highly abstract cognitive abilities each in their own right. This study is the first to provide evidence that visual categories can be ordered serially by macaque monkeys using a behavioral paradigm that provides no explicit feedback about category or serial order. These results strongly challenge accounts of learning based on stimulus–response associations. PMID:28546309

  18. Evaluation in Rhesus Monkeys of a Bivalent Live Attenuated Dengue Vaccine Containing Types 2 and 4 Viruses.

    DTIC Science & Technology

    1984-06-01

    previous reports,(1) antibody levels of most of the vaccinated animals declined markedly on or before post vacination day 150. PR13s showed that the EM-4...V.H., Gould, D.J., Chapple, F.E., and Russell, P.K.: Dengue 2 vacine , viremia and Inmune response in rhesus monkeys. Infect. Immun. 27, 181-186, 1980. 2

  19. Urinary excretion of cortisol from rhesus monkeys (Macaca mulatta) habituated to restraint

    NASA Technical Reports Server (NTRS)

    Wade, C. E.; Ortiz, R. M.

    1997-01-01

    Use of monkeys in research has often required that they be restrained in a chair. However, chair restraint can elicit an initial neuroendocrine stress response. Also, inactivity associated with restraint can induce muscular atrophy. We proposed that prior habituation of monkeys to chair restraint would attenuate these neuroendocrine responses without causing substantial muscle wasting. Four rhesus monkeys (Macaca mulatta) were trained and habituated to a restraint chair specifically designed for spaceflight. During the study, monkeys were placed in metabolic cages for 7 days (prerestraint, Phase I), placed in a chair restraint for 18 days (Phase II), and then returned to their metabolic cages for 5 days (postrestraint, Phase III). Urine was collected between 0700-1100 daily, and measurements of cortisol, creatinine, and electrolyte concentrations were adjusted for hourly excretion rates. Body weights of the monkeys did not change between start of the prerestraint and postrestraint phases (10.3 +/- 0.8 vs. 10.3 +/- 0.9 kg, respectively). During the 3 phases, mean excretion rate of cortisol did not change (24.1 +/- 10.3, 26.7 +/- 7.7, and 19.3 +/- 5.8 microg/h, respectively). Mean excretion rate of creatinine (37.3 +/- 7.5, 37.5 +/- 12.2, and 36.9 +/- 17.1 mg/h, respectively), Na+ (3.3 +/- 1.2, 3.2 +/- 1.2, 2.2 +/- 1.8 mmol/h, respectively), and K+ (5.3 +/- 1.8, 5.4 +/- 1.6, and 4.3 +/- 2.8 mmol/h, respectively) were also not altered. Lack of an increase in excreted urinary cortisol suggested that prior habituation to chair restraint attenuated neuroendocrine responses reported previously. Also, the chair restraint method used appeared to allow adequate activity, because the monkeys did not have indices of muscle wasting.

  20. Attenuation of cocaine self-administration by chronic oral phendimetrazine in rhesus monkeys.

    PubMed

    Czoty, P W; Blough, B E; Fennell, T R; Snyder, R W; Nader, M A

    2016-06-02

    Chronic treatment with the monoamine releaser d-amphetamine has been consistently shown to decrease cocaine self-administration in laboratory studies and clinical trials. However, the abuse potential of d-amphetamine is an obstacle to widespread clinical use. Approaches are needed that exploit the efficacy of the agonist approach but avoid the abuse potential associated with dopamine releasers. The present study assessed the effectiveness of chronic oral administration of phendimetrazine (PDM), a pro-drug for the monoamine releaser phenmetrazine (PM), to decrease cocaine self-administration in four rhesus monkeys. Each day, monkeys pressed a lever to receive food pellets under a 50-response fixed-ratio (FR) schedule of reinforcement and self-administered cocaine (0.003-0.56 mg/kg per injection, i.v.) under a progressive-ratio (PR) schedule in the evening. After completing a cocaine self-administration dose-response curve, sessions were suspended and PDM was administered (1.0-9.0 mg/kg, p.o., b.i.d.). Cocaine self-administration was assessed using the PR schedule once every 7 days while food-maintained responding was studied daily. When a persistent decrease in self-administration was observed, the cocaine dose-effect curve was re-determined. Daily PDM treatment decreased cocaine self-administration by 30-90% across monkeys for at least 4 weeks. In two monkeys, effects were completely selective for cocaine. Tolerance developed to initial decreases in food-maintained responding in the third monkey and in the fourth subject, fluctuations were observed that were lower in magnitude than effects on cocaine self-administration. Cocaine dose-effect curves were shifted down and/or rightward in three monkeys. These data provide further support for the use of agonist medications for cocaine abuse, and indicate that the promising effects of d-amphetamine extend to a more clinically viable pharmacotherapy. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Exposure to Sunlight Reduces the Risk of Myopia in Rhesus Monkeys

    PubMed Central

    Wang, Yong; Ding, Hui; Stell, William K.; Liu, Liangping; Li, Saiqun; Liu, Hongshan; Zhong, Xingwu

    2015-01-01

    Exposure to sunlight has recently been postulated as responsible for the effect that more time spent outdoors protects children from myopia, while early life exposure to natural light was reported to be possibly related to onset of myopia during childhood. In this study, we had two aims: to determine whether increasing natural light exposure has a protective effect on hyperopic defocus-induced myopia, and to observe whether early postnatal exposure to natural light causes increased risk of refractive error in adolescence. Eight rhesus monkeys (aged 20-30 days) were treated monocularly with hyperopic-defocus (-3.0D lens) and divided randomly into two groups: AL group (n=4), reared under Artificial (indoor) Lighting (08:00-20:00); and NL group (n=4), exposed to Natural (outdoor) Light for 3 hours per day (11:00-14:00), and to indoor lighting for the rest of the light phase. After being reared with lenses for ca. 190 days, all monkeys were returned to unrestricted vision until the age of 3 years. Another eight age-matched monkeys, reared with unrestricted vision under artificial lighting since birth, were employed as controls. The ocular refraction, corneal curvature and axial dimensions were measured before lens-wearing (at 23±3 days of age), monthly during the light phase, and at the age of puberty (at 1185+3 days of age). During the lens-wearing treatment, infant monkeys in the NL group were more hyperopic than those in the AL group (F=5.726, P=0.032). Furthermore, the two eyes of most NL monkeys remained isometropic, whereas 3 of 4 AL monkeys developed myopic anisometropia more than -2.0D. At adolescence, eyes of AL monkeys showed significant myopic anisometropia compared with eyes of NL monkeys (AL vs NL: -1.66±0.87D vs -0.22±0.44D; P=0.002) and controls (AL vs Control: -1.66±0.87D vs -0.05±0.85D; P<0.0001). All differences in refraction were associated with parallel changes in axial dimensions. Our results suggest that exposure to natural outdoor light

  2. Reinforcing and discriminative stimulus effects of RTI 111, a 3-phenyltropane analog, in rhesus monkeys: interaction with methamphetamine.

    PubMed

    Ranaldi, R; Anderson, K G; Carroll, F I; Woolverton, W L

    2000-12-01

    The neuronal actions of methamphetamine (MA) include an increase in extracellular levels of monoamines, presumably via reverse transport involving the monoamine transporters. This action is thought to play an important role in the effects of MA. Therefore, in the present experiment, it was hypothesized that a monoamine uptake blocker would block behavioral effects of MA related to its abuse. RTI 111, a newly synthesized 3-phenyltropane analog with high affinity for the dopamine, norepinephrine, and serotonin transporters, was evaluated alone and in combination with MA for its ability to block the reinforcing and discriminative stimulus effects of MA in rhesus monkeys. RTI 111 (0.0003-0.03 mg/kg, i.v.) was made available to four rhesus monkeys for self-administration under a fixed-ratio 25 (FR 25) schedule of reinforcement. RTI 111 (0.01-0.1 mg/kg, i.m.) was also administered as a pretreatment (15 min prior) to four monkeys self-administering MA (0.0-0.3 mg/kg per injection, i.v.) on a progressive-ratio schedule of reinforcement. MA (0.01-1.0 mg/kg, i.m.), RTI 111 (0.001-0.1 mg/kg, i.m.), or the combination of MA and RTI 111 were administered to four monkeys trained to discriminate (+)-amphetamine (AMPH; 1.0 or 1.7 mg/kg, intragastric) from saline. When RTI 111 was made available for self-administration under an FR 25 schedule it functioned as a positive reinforcer in all four monkeys tested. When RTI 111 was given as a pretreatment to monkeys self-administering MA under a progressive-ratio schedule, the MA dose-response function shifted to the left and down. When RTI 111 or MA were given to monkeys trained to discriminate AMPH from saline, full AMPH-like responding was observed for both drugs. Given in combination, RTI 111 shifted the MA dose-response function to the left. These data suggest that RTI 111 is behaviorally similar to traditional psychomotor stimulants that act at the DA transporter and that it increases, rather than blocks, the behavioral potency of

  3. Experience-dependent changes in the development of face preferences in infant rhesus monkeys.

    PubMed

    Parr, Lisa A; Murphy, Lauren; Feczko, Eric; Brooks, Jenna; Collantes, Marie; Heitz, Thomas R

    2016-12-01

    It is well known that early experience shapes the development of visual perception for faces in humans. However, the effect of experience on the development of social attention in non-human primates is unknown. In two studies, we examined the effect of cumulative social experience on developmental changes in attention to the faces of unfamiliar conspecifics or heterospecifics, and mom versus an unfamiliar female. From birth, infant rhesus monkeys preferred to look at conspecific compared to heterospecific faces, but this pattern reversed over time. In contrast, no consistent differences were found for attention to mom's face compared to an unfamiliar female. These results suggest differential roles of social experience in shaping the development of face preferences in infant monkeys. Results have important implications for establishing normative trajectories for the development of face preferences in an animal model of human social behavior. © 2016 Wiley Periodicals, Inc.

  4. Effect of electromagnetic pulse on avoidance behavior and electroencephalogram of a rhesus monkey.

    PubMed

    Mattsson, J L; Oliva, S A

    1976-06-01

    A 12-kg male rhesus monkey was exposed to electromagnetic pulse (EMP) at 266 kv/m, 5 pulses/s, for 1 h (18,700 pulses). The effects of EMP on Sidman avoidance behavior and on post-exposure electroencephalogram were evaluated, and no significant changes were detected. An analysis of an EMP showed that it contained various frequency components extending from 0 Hz to 10(9) Hz. However, the pulse configuration was such that its power was mainly confined to the longer wave-lengths (less than 30 MHz). The lack of biologic effect was attributed to the fact that the wavelengths were long relative to the size of the monkey, and little energy deposition was likely to occur. In addition, the electric field was evenly distributed across all lower frequencies so that only a very small electric field component existed at any specific low frequency.

  5. Attentional biases and memory for emotional stimuli in men and male rhesus monkeys.

    PubMed

    Lacreuse, Agnès; Schatz, Kelly; Strazzullo, Sarah; King, Hanna M; Ready, Rebecca

    2013-11-01

    We examined attentional biases for social and non-social emotional stimuli in young adult men and compared the results to those of male rhesus monkeys (Macaca mulatta) previously tested in a similar dot-probe task (King et al. in Psychoneuroendocrinology 37(3):396-409, 2012). Recognition memory for these stimuli was also analyzed in each species, using a recognition memory task in humans and a delayed non-matching-to-sample task in monkeys. We found that both humans and monkeys displayed a similar pattern of attentional biases toward threatening facial expressions of conspecifics. The bias was significant in monkeys and of marginal significance in humans. In addition, humans, but not monkeys, exhibited an attentional bias away from negative non-social images. Attentional biases for social and non-social threat differed significantly, with both species showing a pattern of vigilance toward negative social images and avoidance of negative non-social images. Positive stimuli did not elicit significant attentional biases for either species. In humans, emotional content facilitated the recognition of non-social images, but no effect of emotion was found for the recognition of social images. Recognition accuracy was not affected by emotion in monkeys, but response times were faster for negative relative to positive images. Altogether, these results suggest shared mechanisms of social attention in humans and monkeys, with both species showing a pattern of selective attention toward threatening faces of conspecifics. These data are consistent with the view that selective vigilance to social threat is the result of evolutionary constraints. Yet, selective attention to threat was weaker in humans than in monkeys, suggesting that regulatory mechanisms enable non-anxious humans to reduce sensitivity to social threat in this paradigm, likely through enhanced prefrontal control and reduced amygdala activation. In addition, the findings emphasize important differences in

  6. Looking ahead? Computerized maze task performance by chimpanzees (Pan troglodytes), rhesus monkeys (Macaca mulatta), capuchin monkeys (Cebus apella), and human children (Homo sapiens).

    PubMed

    Beran, Michael J; Parrish, Audrey E; Futch, Sara E; Evans, Theodore A; Perdue, Bonnie M

    2015-05-01

    Human and nonhuman primates are not mentally constrained to the present. They can remember the past and-at least to an extent-anticipate the future. Anticipation of the future ranges from long-term prospection such as planning for retirement to more short-term future-oriented cognition such as planning a route through a maze. Here we tested a great ape species (chimpanzees), an Old World monkey species (rhesus macaques), a New World monkey species (capuchin monkeys), and human children on a computerized maze task. All subjects had to move a cursor through a maze to reach a goal at the bottom of the screen. For best performance on the task, subjects had to "plan ahead" to the end of the maze to move the cursor in the correct direction, avoid traps, and reverse directions if necessary. Mazes varied in difficulty. Chimpanzees were better than both monkey species, and monkeys showed a particular deficit when moving away from the goal or changing directions was required. Children showed a similar pattern to monkeys regarding the effects of reversals and moves away from the goal, but their overall performance in terms of correct maze completion was similar to the chimpanzees. The results highlight similarities as well as differences in planning across species and the role that inhibitory control may play in future-oriented cognition in primates. (c) 2015 APA, all rights reserved).

  7. The calcium endocrine system of adolescent rhesus monkeys and controls before and after spaceflight

    NASA Technical Reports Server (NTRS)

    Arnaud, Sara B.; Navidi, Meena; Deftos, Leonard; Thierry-Palmer, Myrtle; Dotsenko, Rita; Bigbee, Allison; Grindeland, Richard E.

    2002-01-01

    The calcium endocrine system of nonhuman primates can be influenced by chairing for safety and the weightless environment of spaceflight. The serum of two rhesus monkeys flown on the Bion 11 mission was assayed pre- and postflight for vitamin D metabolites, parathyroid hormone, calcitonin, parameters of calcium homeostasis, cortisol, and indexes of renal function. Results were compared with the same measures from five monkeys before and after chairing for a flight simulation study. Concentrations of 1,25-dihydroxyvitamin D were 72% lower after the flight than before, and more than after chairing on the ground (57%, P < 0.05). Decreases in parathyroid hormone did not reach significance. Calcitonin showed modest decreases postflight (P < 0.02). Overall, effects of spaceflight on the calcium endocrine system were similar to the effects of chairing on the ground, but were more pronounced. Reduced intestinal calcium absorption, losses in body weight, increases in cortisol, and higher postflight blood urea nitrogen were the changes in flight monkeys that distinguished them from the flight simulation study animals.

  8. Tetanus antibody titers and duration of immunity to clinical tetanus infections in free-ranging rhesus monkeys (Macaca mulatta).

    PubMed

    Kessler, Matthew J; Berard, John D; Rawlins, Richard G; Bercovitch, Fred B; Gerald, Melissa S; Laudenslager, Mark L; Gonzalez-Martinez, Janis

    2006-07-01

    Prior to 1985 tetanus was a major cause of mortality in the free-ranging colony of rhesus monkeys on Cayo Santiago, accounting for almost a quarter of annual deaths. In 1985 and 1986 all animals (except infants) received primary and booster doses, respectively, of tetanus toxoid. In subsequent years primary immunizations were given to all yearlings, and boosters were administered to all 2-year-old animals during the annual capture of the colony. The main objectives of the tetanus immunization program were to reduce the pain and suffering caused by tetanus infections and to decrease mortality in the colony. Other objectives were to evaluate the efficacy of the two-dose tetanus toxoid immunization protocol and to determine whether additional boosters might be required to provide adequate long-term protection against tetanus infections. The immediate effect of the mass immunization program was the elimination of clinical tetanus infections in the population and a 42.2% reduction in the overall mortality rate. Since the immunization program began, no cases of tetanus have been observed in the colony, except in two unimmunized infants, and it has not been necessary to give tertiary injections of tetanus toxoid to maintain protection against infection. A sample collected in 2004 of the original cohort of monkeys immunized in 1985 and 1986 showed that 93.3% (14/15) had protective tetanus antibody titers (>0.01 IU/ml) at the ages of 20-23 years, which is close to the life expectancy of the Cayo Santiago rhesus macaques. Two intramuscular doses of tetanus toxoid provided long-term, if not lifelong, protection against tetanus for rhesus monkeys living in a tropical clime where tetanus is enzootic and the risk of infection is great. (c) 2005 Wiley-Liss, Inc.

  9. Pharmacologically and Edinger-Westphal stimulated accommodation in rhesus monkeys does not rely on changes in anterior chamber pressure.

    PubMed

    He, Lin; Wendt, Mark; Glasser, Adrian

    2014-08-01

    This study was undertaken to understand the role of anterior chamber pressure (ACP) during pharmacological and Edinger-Westphal (EW) stimulated accommodation in anesthetized monkeys. Experiments were performed on one iridectomized eye each of 7 anesthetized adolescent rhesus monkeys. Accommodation was induced by EW stimulation (n = 2) and intravenous administration of 0.25-4.0 mg/kg pilocarpine (n = 6). Accommodative refractive and biometric changes were measured with continuous 60 Hz infrared photorefraction (n = 6) and 100 Hz A-scan ultrasound biometry (n = 1). An ocular perfusion system was used to measure and manipulate ACP. Pressure was recorded via a 27-gauge needle in the anterior chamber connected to a pressure transducer (n = 7). The needle was also connected to a fluid reservoir to allow ACP to be manipulated and clamped (n = 4) by raising or lowering the fluid reservoir. In all six pharmacologically stimulated monkeys ACP increased during accommodation, from 0.70 to 2.38 mmHg, four of which showed pressure decreases preceding the pressure increases. Two eyes also showed increases in ACP during EW-stimulated accommodation of 2.8 and 7.2 mmHg. ACP increased with increasing EW stimulus amplitudes (n = 2). Clamping or externally manipulating ACP had no effect on resting refraction or on EW and pharmacologically stimulated accommodation in four eyes. The results show that EW stimulated and pharmacologically stimulated accommodation do not rely on ACP in rhesus monkeys. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. On the nature of directed behavior to drug-associated light cues in rhesus monkeys (Macaca mulatta).

    PubMed

    Reilly, Mark P; Berndt, Sonja I; Woods, James H

    2016-11-01

    The present study investigated the role of drug-paired stimuli in controlling the behavior of rhesus monkeys. Systematic observations were made with nine monkeys who had a history of drug self-administration; they had been lever pressing to produce intravenous infusions of various drugs. These observations revealed that the stimulus light co-occurring with drug infusion produced robust and cue-directed behavior such as orienting, touching and biting. Experiment 1 showed that this light-directed behavior would occur in naïve monkeys exposed to a Pavlovian pairing procedure. Four monkeys were given response-independent injections of cocaine. In two monkeys, a red light preceded cocaine injections by 5 s, and a green light co-occurred with the 5-s cocaine injections. In the other two monkeys, the light presentations and cocaine injections occurred independently. Light-directed behavior occurred in all four monkeys within the first couple of trials and at high levels but decreased across sessions. The cocaine-paired stimulus maintained behavior longer and at higher levels than the uncorrelated stimuli. Furthermore, light-directed behavior was not maintained when cocaine was replaced with saline. Light-directed behavior did not occur in the absence of the lights. When these monkeys were subsequently trained to lever press for cocaine, light-directed behavior increased to levels higher than previously observed. Behavior directed towards drug-paired stimuli is robust, reliable and multiply determined; the mechanisms underlying this activity likely include Pavlovian conditioning, stimulus novelty, habituation and operant conditioning.

  11. Comparison between Surrogate Indexes of Insulin Sensitivity/Resistance and Hyperinsulinemic Euglycemic Glucose Clamps in Rhesus Monkeys

    PubMed Central

    Lee, Ho-Won; Muniyappa, Ranganath; Yan, Xu; Yue, Lilly Q.; Linden, Ellen H.; Chen, Hui; Hansen, Barbara C.

    2011-01-01

    The euglycemic glucose clamp is the reference method for assessing insulin sensitivity in humans and animals. However, clamps are ill-suited for large studies because of extensive requirements for cost, time, labor, and technical expertise. Simple surrogate indexes of insulin sensitivity/resistance including quantitative insulin-sensitivity check index (QUICKI) and homeostasis model assessment (HOMA) have been developed and validated in humans. However, validation studies of QUICKI and HOMA in both rats and mice suggest that differences in metabolic physiology between rodents and humans limit their value in rodents. Rhesus monkeys are a species more similar to humans than rodents. Therefore, in the present study, we evaluated data from 199 glucose clamp studies obtained from a large cohort of 86 monkeys with a broad range of insulin sensitivity. Data were used to evaluate simple surrogate indexes of insulin sensitivity/resistance (QUICKI, HOMA, Log HOMA, 1/HOMA, and 1/Fasting insulin) with respect to linear regression, predictive accuracy using a calibration model, and diagnostic performance using receiver operating characteristic. Most surrogates had modest linear correlations with SIClamp (r ≈ 0.4–0.64) with comparable correlation coefficients. Predictive accuracy determined by calibration model analysis demonstrated better predictive accuracy of QUICKI than HOMA and Log HOMA. Receiver operating characteristic analysis showed equivalent sensitivity and specificity of most surrogate indexes to detect insulin resistance. Thus, unlike in rodents but similar to humans, surrogate indexes of insulin sensitivity/resistance including QUICKI and log HOMA may be reasonable to use in large studies of rhesus monkeys where it may be impractical to conduct glucose clamp studies. PMID:21209021

  12. Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys.

    PubMed

    Johnson, Amy R; Banks, Matthew L; Blough, Bruce E; Lile, Joshua A; Nicholson, Katherine L; Negus, S Stevens

    2016-08-01

    Homologous cocaine self-administration procedures in laboratory animals and humans may facilitate translational research for medications development to treat cocaine dependence. This study, therefore, sought to establish choice between cocaine and an alternative reinforcer in rhesus monkeys responding under a procedure back-translated from previous human studies and homologous to a human laboratory procedure described in a companion paper. Four rhesus monkeys with chronic indwelling intravenous catheters had access to cocaine injections (0, 0.043, 0.14, or 0.43mg/kg/injection) and food (0, 1, 3, or 10 1g banana-flavored food pellets). During daily 5h sessions, a single cocaine dose and a single food-reinforcer magnitude were available in 10 30-min trials. During the initial "sample" trial, the available cocaine and food reinforcer were delivered non-contingently. During each of the subsequent nine "choice" trials, responding could produce either the cocaine or food reinforcer under an independent concurrent progressive-ratio schedule. Preference was governed by the cocaine dose and food-reinforcer magnitude, and increasing cocaine doses produced dose-dependent increases in cocaine choice at all food-reinforcer magnitudes. Effects of the candidate medication lisdexamfetamine (0.32-3.2mg/kg/day) were then examined on choice between 0.14mg/kg/injection cocaine and 10 pellets. Under baseline conditions, this reinforcer pair maintained an average of approximately 6 cocaine and 3 food choices. Lisdexamfetamine dose-dependently decreased cocaine choice in all monkeys, but food choice was not significantly altered. These results support utility of this procedure in rhesus monkeys as one component of a platform for translational research on medications development to treat cocaine use disorder. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Task switching in rhesus macaques (Macaca mulatta) and tufted capuchin monkeys (Cebus apella) during computerized categorization tasks.

    PubMed

    Smith, Travis R; Beran, Michael J

    2018-05-31

    The present experiments extended to monkeys a previously used abstract categorization procedure (Castro & Wasserman, 2016) where pigeons had categorized arrays of clipart icons based upon two task rules: the number of clipart objects in the array or the variability of objects in the array. Experiment 1 replicated Castro and Wasserman by using capuchin monkeys and rhesus monkeys and reported that monkeys' performances were similar to pigeons' in terms of acquisition, pattern of errors, and the absence of switch costs. Furthermore, monkeys' insensitivity to the added irrelevant information suggested that an associative (rather than rule-based) categorization mechanism was dominant. Experiment 2 was conducted to include categorization cue reversals to determine (a) whether the monkeys would quickly adapt to the reversals and inhibit interference from a prereversal task rule (consistent with a rule-based mechanism) and (b) whether the latency to make a response prior to a correct or incorrect outcome was informative about the presence of a cognitive mechanism. The cue reassignment produced profound and long-lasting performance deficits, and a long reacquisition phase suggested the involvement of associative learning processes; however, monkeys also displayed longer latencies to choose prior to correct responses on challenging trials, suggesting the involvement of nonassociative processes. Together these performances suggest a mix of associative and cognitive-control processes governing monkey categorization judgments. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  14. Clustering of PCOS-like traits in naturally hyperandrogenic female rhesus monkeys.

    PubMed

    Abbott, D H; Rayome, B H; Dumesic, D A; Lewis, K C; Edwards, A K; Wallen, K; Wilson, M E; Appt, S E; Levine, J E

    2017-04-01

    Do naturally occurring, hyperandrogenic (≥1 SD of population mean testosterone, T) female rhesus monkeys exhibit traits typical of women with polycystic ovary syndrome (PCOS)? Hyperandrogenic female monkeys exhibited significantly increased serum levels of androstenedione (A4), 17-hydroxyprogesterone (17-OHP), estradiol (E2), LH, antimullerian hormone (AMH), cortisol, 11-deoxycortisol and corticosterone, as well as increased uterine endometrial thickness and evidence of reduced fertility, all traits associated with PCOS. Progress in treating women with PCOS is limited by incomplete knowledge of its pathogenesis and the absence of naturally occurring PCOS in animal models. A female macaque monkey, however, with naturally occurring hyperandrogenism, anovulation and polyfollicular ovaries, accompanied by insulin resistance, increased adiposity and endometrial hyperplasia, suggests naturally occurring origins for PCOS in nonhuman primates. As part of a larger study, circulating serum concentrations of selected pituitary, ovarian and adrenal hormones, together with fasted insulin and glucose levels, were determined in a single, morning blood sample obtained from 120 apparently healthy, ovary-intact, adult female rhesus monkeys (Macaca mulatta) while not pregnant or nursing. The monkeys were then sedated for somatometric and ultrasonographic measurements. Female monkeys were of prime reproductive age (7.2 ± 0.1 years, mean ± SEM) and represented a typical spectrum of adult body weight (7.4 ± 0.2 kg; maximum 12.5, minimum 4.6 kg). Females were defined as having normal (n = 99) or high T levels (n = 21; ≥1 SD above the overall mean, 0.31 ng/ml). Electronic health records provided menstrual and fecundity histories. Steroid hormones were determined by tandem LC-MS-MS; AMH was measured by enzymeimmunoassay; LH, FSH and insulin were determined by radioimmunoassay; and glucose was read by glucose meter. Most analyses were limited to 80 females (60 normal T, 20 high T) in

  15. An experimental vestibular neural prosthesis: design and preliminary results with rhesus monkeys stimulated with modulated pulses.

    PubMed

    Nie, Kaibao; Ling, Leo; Bierer, Steven M; Kaneko, Chris R S; Fuchs, Albert F; Oxford, Trey; Rubinstein, Jay T; Phillips, James O

    2013-06-01

    A vestibular neural prosthesis was designed on the basis of a cochlear implant for treatment of Meniere's disease and other vestibular disorders. Computer control software was developed to generate patterned pulse stimuli for exploring optimal parameters to activate the vestibular nerve. Two rhesus monkeys were implanted with the prototype vestibular prosthesis and they were behaviorally evaluated post implantation surgery. Horizontal and vertical eye movement responses to patterned electrical pulse stimulations were collected on both monkeys. Pulse amplitude modulated (PAM) and pulse rate modulated (PRM) trains were applied to the lateral canal of each implanted animal. Robust slow-phase nystagmus responses following the PAM or PRM modulation pattern were observed in both implanted monkeys in the direction consistent with the activation of the implanted canal. Both PAM and PRM pulse trains can elicit a significant amount of in-phase modulated eye velocity changes and they could potentially be used for efficiently coding head rotational signals in future vestibular neural prostheses.

  16. Postpyloric regulation of gastric emptying in rhesus monkeys.

    PubMed

    McHugh, P R; Moran, T H; Wirth, J B

    1982-09-01

    Saline (0.9% NaCl) empties rapidly and exponentially from the stomach of the rhesus monkey, but glucose solutions empty at a calorie-constant rate of 0.4 kcal/min. By means of indwelling intragastric and intraduodenal cannulae we can demonstrate an inhibition on the delivery of saline from the stomach provoked by glucose placed beyond the pylorus. The inhibition varies directly with the glucose calories in the intestine and averages 2.5 min/kcal. That these two results (0.4 kcal/min and 2.5 min/kcal) are reciprocals suggests a feedback inhibition on the gastric emptying of nutrients arising from beyond the pylorus and adequate to explain the rate of glucose delivery to the intestine. A control theory description of gastric emptying that includes such feedback regulation can be derived from these data to explain the different gastric emptying patterns of nutrients and nonnutrient solutions. These patterns give this visceral system a precision in its management of nutrients that can provide information crucial to preabsorptive satiety.

  17. Comparative Infectivity Determinations of Dengue Virus Vaccine Candidates in Rhesus Monkeys, Mosquitoes, and Cell Cultures

    DTIC Science & Technology

    1993-01-28

    34 are required for the evaluation of these vaccine candidates. RE: DAMDI7-89-C-9175 Page 16 REFERENCES 1. Sabin AB, Sclesinger RW, 1945. Production of...AD-A261 892 CONTRACT NO: DAMD17-89-C-9 175 \\II\\IllI\\I\\I1\\\\~il\\ TITLE: COMPARATIVE INFECTIVITY DETERMINATIONS OF DENGUE VIRUS VACCINE CANDIDATES IN... Vaccine Candidates in Rhesus Monkeys, 63002A Mosquitoes, and Cell Cultures 3M263002D870 AC 6. AUTHOR(S) DA335475 Edmundo Kraiselburd 7. PERFORMING

  18. Short-term testosterone manipulations modulate visual recognition memory and some aspects of emotional reactivity in male rhesus monkeys.

    PubMed

    Lacreuse, Agnès; Gore, Heather E; Chang, Jeemin; Kaplan, Emily R

    2012-05-15

    The role of testosterone (T) in modulating cognitive function and emotion in men remains unclear. The paucity of animal studies has likely contributed to the slow progress in this area. In particular, studies in nonhuman primates have been lacking. Our laboratory has begun to address this issue by pharmacologically manipulating T levels in intact male rhesus monkeys, using blind, placebo-controlled, crossover designs. We previously found that T-suppressed monkeys receiving supraphysiological T for 4 weeks had lower visual recognition memory for long delays and enhanced attention to videos of negative social stimuli (Lacreuse et al., 2009, 2010) compared to when treated with oil. To further delineate the conditions under which T affects cognition and emotion, the present study focused on the short-term effects of physiological T. Six intact males were treated with the gonadotropin-releasing hormone antagonist degarelix (3 mg/kg) for 7 days and received one injection of T enanthate (5 mg/kg) followed by one injection of oil vehicle 7 days later (n=3), or the reverse treatment (n=3). Performance on two computerized tasks, the Delayed-non-matching-to-sample (DNMS) with random delays and the object-Delayed Recognition Span test (object-DRST) and one task of emotional reactivity, an approach/avoidance task of negative, familiar and novel objects, was examined at baseline and 3-5 days after treatment. DNMS performance was significantly better when monkeys were treated with T compared to oil, independently of the delay duration or the nature (emotional or neutral) of the stimuli. Performance on the object-DRST was unaffected. Interestingly, subtle changes in emotional reactivity were also observed: T administration was associated with fewer object contacts, especially on negative objects, without overt changes in anxious behaviors. These results may reflect increased vigilance and alertness with high T. Altogether, the data suggest that changes in general arousal may

  19. Exploring the extent and function of higher-order auditory cortex in rhesus monkeys.

    PubMed

    Poremba, Amy; Mishkin, Mortimer

    2007-07-01

    Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques, cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left-hemisphere "dominance" during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole "dominance" appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys.

  20. Exploring the extent and function of higher-order auditory cortex in rhesus monkeys

    PubMed Central

    Mishkin, Mortimer

    2009-01-01

    Just as cortical visual processing continues far beyond the boundaries of early visual areas, so too does cortical auditory processing continue far beyond the limits of early auditory areas. In passively listening rhesus monkeys examined with metabolic mapping techniques, cortical areas reactive to auditory stimulation were found to include the entire length of the superior temporal gyrus (STG) as well as several other regions within the temporal, parietal, and frontal lobes. Comparison of these widespread activations with those from an analogous study in vision supports the notion that audition, like vision, is served by several cortical processing streams, each specialized for analyzing a different aspect of sensory input, such as stimulus quality, location, or motion. Exploration with different classes of acoustic stimuli demonstrated that most portions of STG show greater activation on the right than on the left regardless of stimulus class. However, there is a striking shift to left hemisphere “dominance” during passive listening to species-specific vocalizations, though this reverse asymmetry is observed only in the region of temporal pole. The mechanism for this left temporal pole “dominance” appears to be suppression of the right temporal pole by the left hemisphere, as demonstrated by a comparison of the results in normal monkeys with those in split-brain monkeys. PMID:17321703

  1. Behavioral asymmetries of psychomotor performance in rhesus monkeys (Macaca mulatta) - A dissociation between hand preference and skill

    NASA Technical Reports Server (NTRS)

    Hopkins, William D.; Washburn, David A.; Berke, Leslie; Williams, Mary

    1992-01-01

    Hand preferences were recorded for 35 rhesus monkeys (Macaca mulatta) as they manipulated a joystick in response to 2 computerized tasks. These preferences were then used to contrast 8 left- and 10 right-handed subjects on performance measures of hand skill. Individual hand preferences were found, but no significant population asymmetry was observed across the sample. However, the performance data reveal substantial benefits of right-handedness for joystick manipulation, as this group of monkeys mastered the 2 psychomotor tasks significantly faster than did their left-handed counterparts. The data support earlier reports of a right-hand advantage for joystick manipulation and also support the importance of distinguishing between hand preference and manual performance in research on functional asymmetries.

  2. Suppression of bone resorption by miR-141 in aged rhesus monkeys.

    PubMed

    Yang, Shihua; Zhang, Wenhui; Cai, Mingxiang; Zhang, Yuanxu; Jin, Fujun; Yan, Sen; Baloch, Zulqurain; Fang, Zhihao; Xue, Senren; Tang, Rongping; Xiao, Jia; Huang, Qunshan; Sun, Yao; Wang, Xiaogang

    2018-05-31

    Aging-related osteoporosis is considered as serious public health concern. Approximately 30% of postmenopausal women suffer from osteoporosis, and more than 40% of them risk fragility fractures. Multiple types of drugs have been applied to treat osteoporosis, but they are not ideal due to insufficient curing and adverse side effects. miRNA-based gene therapy is a rapidly developed strategy in disease treatment that presents certain advantages, such as large-scale production, genetic safety and rapid effects. Until now, miRNA drugs have been used in investigations of cancer treatments. However, in primates, miRNA drugs have not yet been reported as candidates for osteoclast-targeting osteoporosis treatment. In addition, the therapeutic efficacy was limited by several shortcomings, such as low efficiency of selective delivery, insufficient expression levels in targeting cells, and unexpected side effects. Here, we identify miR-141 as a critical suppressor of osteoclastogenesis and bone resorption. The expression levels of miR-141 are positively correlated with bone mineral density and negatively correlated with aging of bones in both aged rhesus monkeys (Macaca mulatta) and osteoporotic patients. Selective delivery of miR-141 into osteoclasts of aged rhesus monkeys via a nucleic acid delivery system allowed for a gradual increase in bone mass without significant effects on health behavior and function of primary organs. Furthermore, we found that the functional mechanism of miR-141 is targeting two osteoclast differentiation players, Calcr (calcitonin receptors) and EphA2 (Ephrin type-A receptor 2 precursor). Our study suggests that miRNAs such as miR-141 could play a crucial role in suppressing bone resorption in primates and provide reliable experimental evidence for the clinical application of miRNA in osteoporosis treatment. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  3. Impaired preadipocyte differentiation into adipocytes in subcutaneous abdominal adipose of PCOS-like female rhesus monkeys.

    PubMed

    Keller, Erica; Chazenbalk, Gregorio D; Aguilera, Paul; Madrigal, Vanessa; Grogan, Tristan; Elashoff, David; Dumesic, Daniel A; Abbott, David H

    2014-07-01

    Metabolic characteristics of polycystic ovary syndrome women and polycystic ovary syndrome-like, prenatally androgenized (PA) female monkeys worsen with age, with altered adipogenesis of sc abdominal adipose potentially contributing to age-related adverse effects on metabolism. This study examines whether adipocyte morphology and gene expression in sc abdominal adipose differ between late reproductive-aged PA female rhesus monkeys compared with age-matched controls (C). Subcutaneous abdominal adipose of both groups was obtained for histological imaging and mRNA determination of zinc finger protein 423 (Zfp423) as a marker of adipose stem cell commitment to preadipocytes, and CCAAT/enhancer binding protein (C/EBP)α/peroxisome proliferator-activated receptor (PPAR)δ as well as C/EBPα/PPARγ as respective markers of early- and late-stage differentiation of preadipocytes to adipocytes. In all females combined, serum testosterone (T) levels positively correlated with fasting serum levels of total free fatty acid (r(2) = 0.73, P < .002). PA females had a greater population of small adipocytes vs C (P < .001) in the presence of increased Zfp423 (P < .025 vs C females) and decreased C/EBPα (P < .003, vs C females) mRNA expression. Moreover, Zfp423 mRNA expression positively correlated with circulating total free fatty acid levels during iv glucose tolerance testing (P < .004, r(2) = 0.66), whereas C/EBPα mRNA expression negatively correlated with serum T levels (P < .02, r(2) = 0.43). Gene expression of PPARδ and PPARγ were comparable between groups (P = .723 and P = .18, respectively). Early-to-mid gestational T excess in female rhesus monkeys impairs adult preadipocyte differentiation to adipocytes in sc abdominal adipose and may constrain the ability of this adipose depot to safely store fat with age.

  4. Isolation, molecular cloning and in vitro expression of rhesus monkey (Macaca mulatta) prominin-1.s1 complementary DNA encoding a potential hematopoietic stem cell antigen.

    PubMed

    Husain, S M; Shou, Y; Sorrentino, B P; Handgretinger, R

    2006-10-01

    Human prominin-1 (CD133 or AC133) is an important cell surface marker used to isolate primitive hematopoietic stem cells. The commercially available antibody to human prominin-1 does not recognize rhesus prominin-1. Therefore, we isolated, cloned and characterized the complementary DNA (cDNA) of rhesus prominin-1 gene and determined its coding potential. Following the nomenclature of prominin family of genes, we named this cDNA as rhesus prominin-1.s1. The amino acid sequence data of the putative rhesus prominin-1.s1 could be used in designing antigenic peptides to raise antibodies for use in isolation of pure populations of rhesus prominin-1(+) hematopoietic cells. To the best of our knowledge, there has been no previously published report about the isolation of a prominin-1 cDNA from rhesus monkey (Macaca mulatta).

  5. Performing monkeys of Bangladesh: characterizing their source and genetic variation

    PubMed Central

    Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Akhtar, Sharmin; Kanthaswamy, Sree; Smith, David Glenn

    2016-01-01

    The acquisition and training of monkeys to perform is a century's old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations and may escape from their owners or be released into other populations. In order to determine whether this tradition, that involves the acquisition and movement of animals, has influenced the population structure of free-ranging rhesus macaques in Bangladesh we first characterized the source of these monkeys. Biological samples from 65 performing macaques, collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16%) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89%) were transitions and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise difference for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. Collection of performing monkeys from India was also evident. PMID:26758818

  6. Estrogen Restores Multisynaptic Boutons in the Dorsolateral Prefrontal Cortex while Promoting Working Memory in Aged Rhesus Monkeys.

    PubMed

    Hara, Yuko; Yuk, Frank; Puri, Rishi; Janssen, William G M; Rapp, Peter R; Morrison, John H

    2016-01-20

    Humans and nonhuman primates are vulnerable to age- and menopause- related decline in working memory, a cognitive function reliant on area 46 of the dorsolateral prefrontal cortex (dlPFC). We showed previously that presynaptic mitochondrial number and morphology in monkey dlPFC neurons correlate with working memory performance. The current study tested the hypothesis that the types of synaptic connections these boutons form are altered with aging and menopause in rhesus monkeys and that these metrics may be coupled with mitochondrial measures and working memory. Using serial section electron microscopy, we examined the frequencies and characteristics of nonsynaptic, single-synaptic, and multisynaptic boutons (MSBs) in the dlPFC. In contrast to our previous observations in the monkey hippocampal dentate gyrus, where MSBs comprised ∼40% of boutons, the vast majority of dlPFC boutons were single-synaptic, whereas MSBs constituted a mere 10%. The frequency of MSBs was not altered by normal aging, but decreased by over 50% with surgical menopause induced by ovariectomy in aged monkeys. Cyclic estradiol treatment in aged ovariectomized animals restored MSB frequencies to levels comparable to young and aged premenopausal monkeys. Notably, the frequency of MSBs positively correlated with working memory scores, as measured by the average accuracy on the delayed response (DR) test. Furthermore, MSB incidence positively correlated with the number of healthy straight mitochondria in dlPFC boutons and inversely correlated with the number of pathological donut-shaped mitochondria. Together, our data suggest that MSBs are coupled to cognitive function and mitochondrial health and are sensitive to estrogen. Significance statement: Many aged menopausal individuals experience deficits in working memory, an executive function reliant on recurrent firing of prefrontal cortex (PFC) neurons. However, little is known about the organization of presynaptic inputs to these neurons and how

  7. Shallow discounting of delayed cocaine by male rhesus monkeys when immediate food is the choice alternative.

    PubMed

    Huskinson, Sally L; Myerson, Joel; Green, Leonard; Rowlett, James K; Woolverton, William L; Freeman, Kevin B

    2016-12-01

    Huskinson et al. (2015) recently examined delay discounting in monkeys choosing between an immediate drug (cocaine) reinforcer and a delayed nondrug (food) reinforcer. The present experiment examined the reverse situation: choice between immediate nondrug (food) and delayed drug (cocaine) reinforcers. Whereas the former choice situation exemplifies drug abuse from a delay-discounting perspective, our interest in the latter choice situation is derived from the observation that drug abusers, who characteristically are associated with impulsive choice, typically must devote considerable time to procuring drugs, often at the expense of immediate nondrug alternatives. Accordingly, we analyzed 3 male rhesus monkeys' choices between immediate food and delayed cocaine (0.1 and 0.2 mg/kg/injection) using a hyperbolic model that allowed us to compare discounting rates between qualitatively different reinforcers. Choice of immediate food increased with food amount, and choice functions generally shifted leftward as delay to cocaine increased, indicating a decrease in the subjective value of cocaine. Compared with our previous delay-discounting experiment with immediate cocaine versus delayed food, both doses of delayed cocaine were discounted at a shallow rate. The present results demonstrate that rhesus monkeys will tolerate relatively long delays in an immediate-food versus delayed-drug situation, suggesting that in intertemporal choices between cocaine and food, the subjective value of cocaine is less affected by the delay until reinforcement than is the subjective value of delayed food. More generally, the present findings suggest that although drug abusers may choose impulsively when immediate drug reinforcement is available, they exercise self-control in the acquisition of a highly preferred, delayed drug reinforcer. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  8. Remote and chronic access to the third cerebral ventricle of the unrestrained prepubertal rhesus monkey.

    PubMed

    Gay, V L; Mikuma, N; Plant, T M

    1993-03-01

    One channel of a commercially available standard-size three-channel fluid swivel was modified to permit continuous access to the brain of unrestrained prepubertal rhesus monkeys via a continuous length of small-bore Teflon tube originating from a swivel device on top of the animal's cage and terminating in the third cerebral ventricle. This system was employed to achieve continuous access to the third cerebroventricle in four monkeys for periods of up to 12 mo. The value of the system for studies of the neurochemical control of hypothalamic-releasing factor secretion was established by monitoring adenohypophysial responses to neurotransmitter receptor agonists infused into the third ventricle. Specifically, repetitive infusions of morphine (30 micrograms/infusion) elicited a robust train of prolactin discharges, and third ventricular administration of N-methyl-DL-aspartic acid (NMA; 20 micrograms) resulted in striking discharges of LH.

  9. The effects of horizontal body casting on blood volume, drug responsiveness, and +Gz tolerance in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Dickey, D. T.; Billman, G. E.; Teoh, K.; Sandler, H.; Stone, H. L.

    1982-01-01

    To simulate the weightless condition, eight rhesus monkeys, instrumented with solid-state pressure transducers, were horizontally restrained in body casts for 28 days. Blood volume decreased an average of 13% after 14 days of restraint, due mainly to a drop in plasma volume. Aortic pressure and heart rate responses to norepinephrine and phenylephrine decreased after 14 days of restraint. The monkeys did not show a statistically significant decreased tolerance to a 90 deg sudden upright tilt after horizontal restraint. During the fifth week of casting, four animals were subjected to +Gz acceleration tests on a centrifuge. The acceleration tolerance of the casted monkeys was significantly reduced compared to four similarly instrumented control animals. These findings indicate that the cardiovascular deconditioning associated with simulated weightlessness results from an inability to maintain central blood volume during orthostatic stress.

  10. Prenatal iron deficiency and monoamine oxidase A (MAOA) polymorphisms: combined risk for later cognitive performance in rhesus monkeys.

    PubMed

    Golub, Mari; Hogrefe, Casey

    2014-03-01

    Monoamine oxidase A (MAOA) gene polymorphisms resulting in high and low transcription rates are associated with individual differences in reward efficacy and response inhibition. Iron deficiency (ID) is the most frequent single-nutrient deficiency worldwide, and prenatal ID has recently been shown to carry a risk for lower mental development scores in infants. In this study, a potential interaction of MAOA genotype and prenatal ID was studied in young male rhesus monkeys. Cognitive tasks, including problem solving, responsiveness to reward and attention, were used to characterize the potential interaction of these two fetal risks. ID was induced by feeding rhesus monkey dams an iron-deficient (10 ppm, ID) or an iron-sufficient (100 ppm, IS) diet during gestation (n = 10/group). Subgroups of the ID and IS diet offspring had low-MAOA or high-MAOA transcription rate polymorphisms. ID combined with low-MAOA genotype showed distinctive effects on reward preference and problem solving while ID in hi-MAOA juveniles modified response inhibition. Given the incidence of ID and MAOA polymorphisms in humans, this interaction could be a significant determinant of cognitive performance.

  11. Repeated episodes of ozone inhalation amplifies the effects of allergen sensitization and inhalation on airway immune and structural development in Rhesus monkeys.

    PubMed

    Schelegle, Edward S; Miller, Lisa A; Gershwin, Laurel J; Fanucchi, Michelle V; Van Winkle, Laura S; Gerriets, Joan E; Walby, William F; Mitchell, Valerie; Tarkington, Brian K; Wong, Viviana J; Baker, Gregory L; Pantle, Lorraine M; Joad, Jesse P; Pinkerton, Kent E; Wu, Reen; Evans, Michael J; Hyde, Dallas M; Plopper, Charles G

    2003-08-15

    Twenty-four infant rhesus monkeys (30 days old) were exposed to 11 episodes of filtered air (FA), house dust mite allergen aerosol (HDMA), ozone (O3), or HDMA + O3 (5 days each followed by 9 days of FA). Ozone was delivered for 8 h/day at 0.5 ppm. Twelve of the monkeys were sensitized to house dust mite allergen (Dermatophagoides farinae) at ages 14 and 28 days by subcutaneous inoculation (SQ) of HDMA in alum and intraperitoneal injection of heat-killed Bordetella pertussis cells. Sensitized monkeys were exposed to HDMA aerosol for 2 h/day on days 3-5 of either FA (n = 6) or O3 (n = 6) exposure. Nonsensitized monkeys were exposed to either FA (n = 6) or O3 (n = 6). During the exposure regimen, parameters of allergy (i.e., serum IgE, histamine, and eosinophilia), airways resistance, reactivity, and structural remodeling were evaluated. Eleven repeated 5-day cycles of inhaling 0.5 ppm ozone over a 6-month period had only mild effects on the airways of nonsensitized infant rhesus monkeys. Similarly, the repeated inhalation of HDMA by HDMA-sensitized infant monkeys resulted in only mild airway effects, with the exception of a marked increase in proximal airway and terminal bronchiole content of eosinophils. In contrast, the combined cyclic inhalation of ozone and HDMA by HDMA sensitized infants monkeys resulted in a marked increase in serum IgE, serum histamine, and airways eosinophilia. Furthermore, combined cyclic inhalation of ozone and HDMA resulted in even greater alterations in airway structure and content that were associated with a significant elevation in baseline airways resistance and reactivity. These results suggest that ozone can amplify the allergic and structural remodeling effects of HDMA sensitization and inhalation.

  12. Effects of chronic copper exposure during early life in rhesus monkeys.

    PubMed

    Araya, Magdalena; Kelleher, Shannon L; Arredondo, Miguel A; Sierralta, Walter; Vial, María Teresa; Uauy, Ricardo; Lönnerdal, Bo

    2005-05-01

    Whether infants regulate copper absorption and the potential effects of excess copper in early life remain poorly defined. The objective of the study was to assess copper retention, liver copper content, and liver function in infant rhesus monkeys fed infant formula containing 6.6 mg Cu/L. From birth to 5 mo of age, infant rhesus monkeys were fed formula that was supplemented with copper (0.6 mg Cu/L; n = 5) or not supplemented (n = 4). In all animals, weight and crown-rump length (by anthropometry), hemoglobin, hematocrit, plasma ceruloplasmin activity, and zinc and copper concentrations were measured monthly (birth to 6 mo) and at 8 and 12 mo. When the animals were 1, 5, and 8 mo old, liver copper and metallothionein concentrations, liver histology (by light and electron microscopy), and the number of Kupffer cells were assessed, and 67Cu retention was measured. Liver function was assessed by measurement of plasma alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, and alkaline phosphatase activities and protein, albumin, bilirubin, and blood urea nitrogen concentrations. 67Cu retention was 19.2% and 10.9% after 1 and 5 mo of copper treatment, respectively, compared with approximately 75% in controls at age 2 mo. At age 8 mo, 67Cu retention was 22.9% in copper-treated animals and 31.5% in controls. Liver histology remained normal by light microscopy, with mild ultrastructural signs of cell damage at 5 mo. Liver copper concentration was 4711, 1139, and 498 microg/g dry tissue at 1, 5, and 8 mo, respectively, in copper-treated animals and 250 microg/g at 2 mo in controls. Measurements could not be completed in all animals. No clinical evidence of copper toxicity was observed. Copper absorption was down-regulated; increases in liver copper content at ages 1 and 5 mo did not result in histologic damage. Ultrastructural changes at age 5 mo could signal early cellular damage.

  13. Performing monkeys of Bangladesh: characterizing their source and genetic variation.

    PubMed

    Hasan, M Kamrul; Feeroz, M Mostafa; Jones-Engel, Lisa; Engel, Gregory A; Akhtar, Sharmin; Kanthaswamy, Sree; Smith, David Glenn

    2016-04-01

    The acquisition and training of monkeys to perform is a centuries-old tradition in South Asia, resulting in a large number of rhesus macaques kept in captivity for this purpose. The performing monkeys are reportedly collected from free-ranging populations, and may escape from their owners or may be released into other populations. In order to determine whether this tradition involving the acquisition and movement of animals has influenced the population structure of free-ranging rhesus macaques in Bangladesh, we first characterized the source of these monkeys. Biological samples from 65 performing macaques collected between January 2010 and August 2013 were analyzed for genetic variation using 716 base pairs of mitochondrial DNA. Performing monkey sequences were compared with those of free-ranging rhesus macaque populations in Bangladesh, India and Myanmar. Forty-five haplotypes with 116 (16 %) polymorphic nucleotide sites were detected among the performing monkeys. As for the free-ranging rhesus population, most of the substitutions (89 %) were transitions, and no indels (insertion/deletion) were observed. The estimate of the mean number of pair-wise differences for the performing monkey population was 10.1264 ± 4.686, compared to 14.076 ± 6.363 for the free-ranging population. Fifteen free-ranging rhesus macaque populations were identified as the source of performing monkeys in Bangladesh; several of these populations were from areas where active provisioning has resulted in a large number of macaques. The collection of performing monkeys from India was also evident.

  14. THE EFFECT OF IONIZING RADIATION ON ACETYLCHOLINE METABOLISM IN MACACA- RHESUS MONKEYS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Demin, N.N.; Korneeva, N.V.; Shaternikov, V.A.

    1961-11-01

    In macaca-rhesus monkeys the normal content of free acetylcholine in the mucosa of the small intestine was higher, as it was in brain and liver, than bound acetyl choline. The total cholinesterase activity and, particularly, the activity of acetylcholinesterase and non-specific cholinesterase in control monkeys is highest in brain, followed by intestinal mucosa and liver. One to three days after gamma -irradiation of the monkey at a dose of 600 r the amount of free and bound acetylcholine in the mucosa of the small intestine increased, while it decreased in liver. The total cholinesterase activity in the mucosa of themore » small intestine during this period increased, in general because of the increase in the activity of non-specific cholinesterase. In the liver the increase in total cholinesterase activity also occurred because of an increase in non-specific cholinesterase activity, but was less clear-cut and occurred later (the third day after irradiation). In animals irradiated 2 to 3 years before the investigation, an increased concentration of free acetylcholine in brain, liver, and mucosa of the small intestine was noted; but there were no ehanges in bound acetylcholine. The total cholinesterase activity increased in liver as a result of acetyl cholinesterase increase and non-specific enzymes, and in mucosa of the small intestine only as a result of acetylcholinesterase activity. In brain the total cholinesterase activity decreased as a consequence of a decrease in acetylcholinesterase activity. (auth)« less

  15. Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys.

    PubMed

    Collins, Gregory T; Gerak, Lisa R; Javors, Martin A; France, Charles P

    2016-01-01

    Cocaine abuse and obesity are serious public health problems, and studies suggest that both dopamine and serotonin systems are involved in regulating the consumption of drugs and food. Lorcaserin has serotonin (5-HT)2C receptor agonist actions, is approved by the U.S. Food and Drug Administration for treating obesity, and might be effective for treating cocaine abuse. These studies characterized the pharmacokinetic and behavioral profiles of lorcaserin (intragastric administration) and determined the effectiveness of lorcaserin to alter discriminative stimulus and reinforcing effects of cocaine (intravenous administration) in rhesus monkeys. Administered acutely, lorcaserin dose-dependently increased the occurrence of yawning while decreasing spontaneous activity and operant responding for food. These effects appeared within 30-60 minutes of administration and began to dissipate by 240 minutes, a time course closely matching plasma concentrations of lorcaserin. In monkeys discriminating cocaine from saline, lorcaserin alone did not occasion cocaine-appropriate responding but shifted the cocaine dose-response curve to the right and down in two of three monkeys. When administered acutely, lorcaserin dose-dependently decreased the rate at which monkeys responded for infusions of cocaine. When administered chronically, 3.2 mg/kg lorcaserin reduced the rate of cocaine-maintained responding by 50% for the duration of a 14-day treatment period. Together, these results show that lorcaserin attenuates the discriminative stimulus effects of cocaine after acute administration and the reinforcing effects of cocaine after acute and repeated administration, consistent with the view that it might have utility in treating cocaine abuse. Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics.

  16. Lorcaserin Reduces the Discriminative Stimulus and Reinforcing Effects of Cocaine in Rhesus Monkeys

    PubMed Central

    Collins, Gregory T.; Gerak, Lisa R.; Javors, Martin A.

    2016-01-01

    Cocaine abuse and obesity are serious public health problems, and studies suggest that both dopamine and serotonin systems are involved in regulating the consumption of drugs and food. Lorcaserin has serotonin (5-HT)2C receptor agonist actions, is approved by the U.S. Food and Drug Administration for treating obesity, and might be effective for treating cocaine abuse. These studies characterized the pharmacokinetic and behavioral profiles of lorcaserin (intragastric administration) and determined the effectiveness of lorcaserin to alter discriminative stimulus and reinforcing effects of cocaine (intravenous administration) in rhesus monkeys. Administered acutely, lorcaserin dose-dependently increased the occurrence of yawning while decreasing spontaneous activity and operant responding for food. These effects appeared within 30–60 minutes of administration and began to dissipate by 240 minutes, a time course closely matching plasma concentrations of lorcaserin. In monkeys discriminating cocaine from saline, lorcaserin alone did not occasion cocaine-appropriate responding but shifted the cocaine dose-response curve to the right and down in two of three monkeys. When administered acutely, lorcaserin dose-dependently decreased the rate at which monkeys responded for infusions of cocaine. When administered chronically, 3.2 mg/kg lorcaserin reduced the rate of cocaine-maintained responding by 50% for the duration of a 14-day treatment period. Together, these results show that lorcaserin attenuates the discriminative stimulus effects of cocaine after acute administration and the reinforcing effects of cocaine after acute and repeated administration, consistent with the view that it might have utility in treating cocaine abuse. PMID:26534942

  17. Establishment of a rhesus monkey model of chronic temporal lobe epilepsy using repetitive unilateral intra-amygdala kainic acid injections.

    PubMed

    Chi, Yajie; Wu, Bolin; Guan, Jianwei; Xiao, Kuntai; Lu, Ziming; Li, Xiao; Xu, Yuting; Xue, Shan; Xu, Qiang; Rao, Junhua; Guo, Yanwu

    2017-09-01

    Temporal lobe epilepsy (TLE) is a common type of acquired epilepsy refractory to medical treatment. As such, establishing animal models of this disease is critical to developing new and effective treatment modalities. Because of their small head size, rodents are not suitable for comprehensive electroencephalography (EEG) evaluation via scalp or subdural electrodes. Therefore, a larger primate model that closely recapitulates signs of TLE is needed; here we describe a rhesus monkey model resembling chronic TLE. Eight monkeys were divided into two groups: kainic acid (KA) group (n=6) and saline control group (n=2). Intra-amygdala KA injections were performed biweekly via an Ommaya device until obvious epileptiform discharges were recorded. Video-EEG recording was conducted intermittently throughout the experiment using both scalp and subdural electrodes. Brains were then analyzed for Nissl and glial fibrillary acid protein (GFAP) immunostaining. After 2-4 injections of KA (approximately 1.2-2.4mg, 0.12-0.24mg/kg), interictal epileptiform discharges (IEDs) were recorded in all KA-treated animals. Spontaneous recurrent seizures (SRSs) accompanied by symptoms mimicking temporal lobe absence (undetectable without EEG recording), but few mild motor signs, were recorded in 66.7% (four of six) KA-treated animals. Both IEDs and seizures indicated a primary epileptic zone in the right temporal region and contralateral discharges were later detected. Segmental pyramidal cell loss and gliosis were detected in the brain of a KA-treated monkey. Through a modified protocol of unilateral repetitive intra-amygdala KA injections, a rhesus monkey model with similar behavioral and brain electrical features as TLE was developed. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Effects of spatial training on transitive inference performance in humans and rhesus monkeys

    PubMed Central

    Gazes, Regina Paxton; Lazareva, Olga F.; Bergene, Clara N.; Hampton, Robert R.

    2015-01-01

    It is often suggested that transitive inference (TI; if A>B and B>C then A>C) involves mentally representing overlapping pairs of stimuli in a spatial series. However, there is little direct evidence to unequivocally determine the role of spatial representation in TI. We tested whether humans and rhesus monkeys use spatial representations in TI by training them to organize seven images in a vertical spatial array. Then, we presented subjects with a TI task using these same images. The implied TI order was either congruent or incongruent with the order of the trained spatial array. Humans in the congruent condition learned premise pairs more quickly, and were faster and more accurate in critical probe tests, suggesting that the spatial arrangement of images learned during spatial training influenced subsequent TI performance. Monkeys first trained in the congruent condition also showed higher test trial accuracy when the spatial and inferred orders were congruent. These results directly support the hypothesis that humans solve TI problems by spatial organization, and suggest that this cognitive mechanism for inference may have ancient evolutionary roots. PMID:25546105

  19. Comparison of kappa opioids in rhesus monkeys: behavioral effects and receptor binding affinities.

    PubMed

    France, C P; Medzihradsky, F; Woods, J H

    1994-01-01

    Bremazocine, [5R-(5,7,8 beta)]-N-methyl-N-[7-(1-pyrrolidinyl)1-oxaspiro [4,5]dec-8-yl]-4-benzofuranacetamide (Cl-977), (+-)-trans-3,4-dichloro-N- methyl-(2-(pyrrolidin-1-yl)-5-methoxy-1,2,3,4-tetrahydronapth++ +-1-yl benzeneacetamide methanesulfonate (DUP 747), ethylketocyclazocine (EKC), nalorphine, (+/-)-trans-N-methyl-N-[2-(1- pyrrolidnyl)-cyclohexyl]benzo[b]thiophene-4-acetamide (PD117302), trans-(+/-)-3,4-dichloro-N-methyl-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide (U-50,488), (5,7,8 beta)-N-methyl-N[2-(1- pyrrolidinyl), 1-oxaspiro[4,5]dec-8-yl benzeneacetamide (U-69,593) and spiradoline were compared in rhesus monkeys for their discriminative stimulus, analgesic and respiratory effects. Selected compounds also were studied for their binding affinities at mu [[3H](D-Ala2-Me-Phe4,Glyol5)enkephalin], kappa ([3H]U-69,593) and delta [[3H](D-Pen2-D-Pen5) enkephalin], opioid receptors in monkey brain membranes. All compounds substituted completely (> or = 90%) for EKC in monkeys discriminating between EKC and saline, with the exception that DUP 747 produced a maximum of 74% EKC responding. None of the compounds reversed naltrexone responding in morphine-abstinent monkeys; all of the compounds substituted for naltrexone in morphine-treated monkeys discriminating between naltrexone and saline, with the exception that spiradoline produced a maximum of 68% naltrexone responding. Eight compounds produced maximum analgesic effects in a tail withdrawal procedure and quadazocine antagonized these effects; nalorphine did not have analgesic effects, but it antagonized analgesic effects of several other compounds. U-50,488 did not decrease respiratory function, whereas U-69,593 decreased frequency of respiration and volume of respiration to less than 40% of control values; Cl-977, DUP 747, PD117302 and spiradoline had limited effects on respiratory function. Larger doses of each compound increased both respiration and motor activity.

  20. A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments.

    PubMed

    Khachaturian, Mark Haig

    2010-01-01

    Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4-8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic).

  1. A 4-channel 3 Tesla phased array receive coil for awake rhesus monkey fMRI and diffusion MRI experiments

    PubMed Central

    Khachaturian, Mark Haig

    2010-01-01

    Awake monkey fMRI and diffusion MRI combined with conventional neuroscience techniques has the potential to study the structural and functional neural network. The majority of monkey fMRI and diffusion MRI experiments are performed with single coils which suffer from severe EPI distortions which limit resolution. By constructing phased array coils for monkey MRI studies, gains in SNR and anatomical accuracy (i.e., reduction of EPI distortions) can be achieved using parallel imaging. The major challenges associated with constructing phased array coils for monkeys are the variation in head size and space constraints. Here, we apply phased array technology to a 4-channel phased array coil capable of improving the resolution and image quality of full brain awake monkey fMRI and diffusion MRI experiments. The phased array coil is that can adapt to different rhesus monkey head sizes (ages 4–8) and fits in the limited space provided by monkey stereotactic equipment and provides SNR gains in primary visual cortex and anatomical accuracy in conjunction with parallel imaging and improves resolution in fMRI experiments by a factor of 2 (1.25 mm to 1.0 mm isotropic) and diffusion MRI experiments by a factor of 4 (1.5 mm to 0.9 mm isotropic). PMID:21243106

  2. Short-term fasting attenuates the response of the HPG axis to kisspeptin challenge in the adult male rhesus monkey (Macaca mulatta).

    PubMed

    Wahab, Fazal; Aziz, Farzana; Irfan, Shahzad; Zaman, Waheed-Uz; Shahab, Muhammad

    2008-11-07

    In primates, changes in nutritional status affect the hypothalamic-pituitary-gonadal (HPG) axis by still poorly understood mechanisms. Recently, hypothalamic kisspeptin-GPR54 signaling has emerged as a significant regulator of this neuroendocrine axis. The present study was designed to examine whether suppression of the reproductive function by acute food-restriction in a non-human primate is mediated by decreased responsiveness of the HPG axis to endogenous kisspeptin drive. Five intact adult male rhesus monkeys habituated to chair-restraint, received intravenous boli of human kisspeptin-10 (KP10, 50 microg), hCG (50 IU), and vehicle (1 ml) in both fed and 48-h fasting conditions. Plasma concentrations of glucose, cortisol and testosterone (T) were measured by using enzymatic and specific RIAs, respectively. The acute 48-h fasting decreased plasma glucose (P<0.01) and T (P<0.005) levels, and increased cortisol levels (P<0.05). KP10 administration caused a robust stimulation of T secretion in both fed and fasted monkeys. However, mean T concentration and T AUC after KP10 administration were significantly (P<0.01-0.005) reduced in fasted monkeys. Likewise, the time of the first significant increase in post-KP10 T levels was also significantly (P<0.01) delayed. T response to hCG stimulation was similar in fed and fasted monkeys. The present results indicate that under fasting conditions the KP10 induced T response is delayed and suppressed. These data support the notion that fasting-induced suppression of the HPG axis in the adult male rhesus monkey may involve, at least in part, a reduction in the sensitivity of the GnRH neuronal network to endogenous kisspeptin stimulation.

  3. Temporal Discounting and Inter-Temporal Choice in Rhesus Monkeys

    PubMed Central

    Hwang, Jaewon; Kim, Soyoun; Lee, Daeyeol

    2009-01-01

    Humans and animals are more likely to take an action leading to an immediate reward than actions with delayed rewards of similar magnitudes. Although such devaluation of delayed rewards has been almost universally described by hyperbolic discount functions, the rate of this temporal discounting varies substantially among different animal species. This might be in part due to the differences in how the information about reward is presented to decision makers. In previous animal studies, reward delays or magnitudes were gradually adjusted across trials, so the animals learned the properties of future rewards from the rewards they waited for and consumed previously. In contrast, verbal cues have been used commonly in human studies. In the present study, rhesus monkeys were trained in a novel inter-temporal choice task in which the magnitude and delay of reward were indicated symbolically using visual cues and varied randomly across trials. We found that monkeys could extract the information about reward delays from visual symbols regardless of the number of symbols used to indicate the delay. The rate of temporal discounting observed in the present study was comparable to the previous estimates in other mammals, and the animal's choice behavior was largely consistent with hyperbolic discounting. Our results also suggest that the rate of temporal discounting might be influenced by contextual factors, such as the novelty of the task. The flexibility furnished by this new inter-temporal choice task might be useful for future neurobiological investigations on inter-temporal choice in non-human primates. PMID:19562091

  4. Effects of the Monoamine Uptake Inhibitors RTI-112 and RTI-113 on Cocaine- and Food-Maintained Responding in Rhesus Monkeys

    PubMed Central

    SS, Negus; NK, Mello; HL, Kimmel; LL, Howell; FI, Carroll

    2009-01-01

    Cocaine blocks uptake of the monoamines dopamine, serotonin and norepinephrine, and monoamine uptake inhibitors constitute one class of drugs under consideration as candidate “agonist” medications for the treatment of cocaine abuse and dependence. The pharmacological selectivity of monoamine uptake inhibitors to block uptake of dopamine, serotonin and norepinephrine is one factor that may influence the efficacy and/or safety of these compounds as drug abuse treatment medications. To address this issue, the present study compared the effects of 7-day treatment with a non-selective monoamine uptake inhibitor (RTI-112) and a dopamine-selective uptake inhibitor (RTI-113) on cocaine- and food-maintained responding in rhesus monkeys. Monkeys (N=3) were trained to respond for cocaine injections (0.01 mg/kg/inj) and food pellets under a second-order schedule [FR2(VR16:S)] during alternating daily components of cocaine and food availability. Both RTI-112 (0.0032–0.01 mg/kg/hr) and RTI-113 (0.01–0.056 mg/kg/hr) produced dose-dependent, sustained and nearly complete elimination of cocaine self-administration. However, for both drugs, the potency to reduce cocaine self-administration was similar to the potency to reduce food-maintained responding. These findings do not support the hypothesis that pharmacological selectivity to block dopamine uptake is associated with behavioral selectivity to decrease cocaine- vs. food-maintained responding in rhesus monkeys. PMID:18755212

  5. Sensory Processing in Rhesus Monkeys: Developmental Continuity, Prenatal Treatment, and Genetic Influences

    PubMed Central

    Schneider, Mary L.; Moore, Colleen F.; Adkins, Miriam; Barr, Christina S.; Larson, Julie A.; Resch, Leslie M.; Roberts, Andrew

    2017-01-01

    Neonatal sensory processing (tactile and vestibular function) was tested in 78 rhesus macaques from two experiments. At ages 4–5 years, striatal dopamine D2 receptor binding was examined using positron emission tomography. At ages 5–7 years, adult sensory processing was assessed. Findings were: (a) prenatal stress exposure yielded less optimal neonatal sensory processing; (b) animals carrying the short rh5-HTTLPR allele had less optimal neonatal sensory scores than monkeys homozygous for the long allele; (c) neonatal sensory processing was significantly related to striatal D2 receptor binding for carriers of the short allele, but not for animals homozygous for the long allele; and (d) there was moderate developmental continuity in sensory processing from the neonatal period to adulthood. PMID:27338151

  6. Impaired performance on a rhesus monkey neuropsychological testing battery following simian immunodeficiency virus infection.

    PubMed

    Weed, Michael R; Gold, Lisa H; Polis, Ilham; Koob, George F; Fox, Howard S; Taffe, Michael A

    2004-01-01

    Infection with simian immunodeficiency virus (SIV) in macaques provides an excellent model of AIDS including HIV-induced central nervous system (CNS) pathology and cognitive/behavioral impairment. Recently a behavioral test battery has been developed for macaques based on the CANTAB human neuropsychological testing battery. As with human neuropsychological batteries, different tasks are thought to involve different neural substrates, and therefore performance profiles may assess function in particular brain regions. Ten rhesus monkeys were infected with SIV after being trained on two or more of the battery tasks addressing memory (delayed nonmatching to sample, DNMS), spatial working memory (using a self-ordered spatial search task, SOSS), motivation (progressive-ratio, PR), reaction time (RT), and/or fine motor skills (bimanual motor skill, BMS). Performance was compared to that of 9 uninfected monkeys. Overall, some aspect of performance was impaired in all 10 monkeys following infection. Consistent with results in human AIDS patients, individual performance was impaired most often on battery tasks thought to be sensitive to frontostriatal dopaminergic functioning such as SOSS, RT, and BMS. These results further demonstrate the similarity of behavioral impairment produced by SIV and HIV on homologous behavioral tests, and establish the utility of the testing battery for further investigations into the CNS mechanisms of the reported behavioral changes.

  7. Spacelab Life Sciences 3 biomedical research using the Rhesus Research Facility

    NASA Technical Reports Server (NTRS)

    Ballard, R. W.; Searby, N. D.; Stone, L. S.; Hogan, R. P.; Viso, M.; Venet, M.

    1992-01-01

    In 1985, a letter of agreement was signed between the French space agency, CNES, and NASA, formally initiating a joint venture called the RHESUS Project. The goal of this project is to provide a facility to fly rhesus monkeys (Macaca mulatta) to support spaceflight experiments which are applicable but not practical to carry out on human subjects. Biomedical investigations in behavior/performance, immunology/microbiology, muscle physiology, cardiopulmonary physiology, bone/calcium physiology, regulatory physiology, and neurophysiology disciplines will be performed. The Rhesus Research Facility, hardware capable of supporting two adult rhesus monkeys in a microgravity environment, is being developed for a first flight on Spacelab Life Sciences in early 1996.

  8. Local cerebral hypothermia induced by selective infusion of cold lactated ringer's: a feasibility study in rhesus monkeys.

    PubMed

    Wang, Bincheng; Wu, Di; Dornbos Iii, David; Shi, Jingfei; Ma, Yanhui; Zhang, Mo; Liu, Yumei; Chen, Jian; Ding, Yuchuan; Luo, Yinghao; Ji, Xunming

    2016-06-01

    Hypothermia has shown promise as a neuroprotective strategy for stroke. The use of whole body hypothermia has limited clinical utility due to many severe side effects. Selective brain cooling, or local brain hypothermia, has been previously proposed as an alternative treatment strategy. This study investigated the safety, feasibility, and efficacy of selective brain hypothermia induced by local infusion of ice-cold lactated Ringer's solution in rhesus monkeys. Eight male rhesus monkeys were used in this study. Brain temperature in the territory supplied by middle cerebral artery (MCA) was reduced by infusing 100 mL of ice-cold (0 °C) lactated Ringer's solution over 20 min via a micro-catheter placed in the proximal MCA (n = 4). Vital signs and the temperature of the brain and rectum were monitored before and after infusion. Transcranial Doppler, Magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) were used to evaluate cerebral blood flow, cerebrovascular reactivity (CVR), cerebral edema, and vasospasm. Another cohort of rhesus monkeys (n = 4) were used as systemic cooling controls. Oxygen saturation, blood pressure, heart rate, and hematologic analysis of the two groups remained within the normal range after infusion. Mild cerebral hypothermia (<35 °C) was achieved in 10 min (0.3 °C/min) and was maintained for 20 min in local cortex and striatum following local infusion. The average lowest cerebral temperature in the locally cooled animals was 33.9 ± 0.3 °C in the striatum following 20-min infusion. This was not observed in animals cooled by systemic infusion. The decreases in the rectal temperature for local and systemic infusion were 0.5 ± 0.2 °C and 0.5 ± 0.3 °C, respectively. Selective brain cooling did not cause any cerebral edema as determined by MRI or vasospasm in the perfused vessel based on DSA. Selective cerebral hypothermia did not significantly alter CVR. Local infusion of ice-cold lactated Ringer

  9. Long-term mortality and cancer risk in irradiated rhesus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wood, D.H.

    1989-01-01

    Lifetime observations on a group of 358 rhesus monkeys indicate that life expectancy loss from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events is influenced primarily by the dose rather than by the energy of radiation. After 24 years, life expectancy losses from similar surface doses of low-LET (138-2300 MeV) and high-LET (32-55 MeV) protons are not significantly different, but the high-LET protons are associated with more deaths in the early years, while the low-LET protons contribute more to mortality in later years. In males, the most significant cause of lifemore » shortening is nonleukemia cancers. In females, radiation increased the risk of endometriosis (an abnormal proliferation of the lining of the uterus) which resulted in significant mortality in the years before early detection and treatment methods were employed. The findings support the 1989 guidelines of the NCRP for maximum permissible radiation exposures in astronauts.« less

  10. Pathogenic properties of enterohepatic Helicobacter spp. isolated from rhesus macaques with intestinal adenocarcinoma

    PubMed Central

    Lertpiriyapong, Kvin; Handt, Laurence; Feng, Yan; Mitchell, Thomas W.; Lodge, Kenneth E.; Shen, Zeli; Dewhirst, Floyd E.; Muthupalani, Sureshkumar

    2014-01-01

    Considerable progress has been made in understanding the roles of Helicobacter pylori in inflammation and gastric cancer; however, far less is known about the roles of enterohepatic Helicobacter species (EHS) in carcinogenesis and their zoonotic or pathogenic potential. We determined the prevalence of EHS infection in a cohort of geriatric rhesus monkeys in which intestinal adenocarcinoma (IAC) is common and investigated the association between EHS infection and IAC. The cohort consisted of 36 animals, 14 of which (age 26–35 years) had IAC. Of the 36 rhesus, 35 (97 %) were positive for EHS using PCR or bacterial isolation from faeces, colonic or tumour tissues. Only a single rhesus, which had IAC, was negative for EHS by all detection methods. The EHS identified by 16S rRNA sequencing in this study were from three Helicobacter taxa: Helicobacter macacae (previously rhesus monkey taxon 1), Helicobacter sp. rhesus monkey taxon 2, previously described from strain MIT 99-5507, and Helicobacter sp. rhesus monkey taxon 4, related to Helicobacter fennelliae. Thirteen of 14 monkeys with IAC were positive for either H. macacae (7/13, 54 %), EHS rhesus monkey taxon 4 (4/13, 31 %) or a mixture of the two EHS (2/13, 15 %). These results indicate that EHS are prevalent among aged rhesus macaques with IAC. Using Helicobacter genus-specific florescent in situ hybridization, EHS were detected on the surface of colonic epithelia of infected monkeys. All Helicobacter isolates, including H. macacae, effectively adhered to, invaded, and significantly induced proinflammatory genes, including IL-8, IL-6, TNF-α and iNOS, while downregulating genes involved in the function of inflammasomes, particularly IL-1β, CASPASE-1, NRLP3, NLRP6 and NLRC4 in the human colonic T84 cell line (P<0.0001). These results suggest that EHS may represent an aetiological agent mediating diarrhoea, chronic inflammation, and possibly intestinal cancer in non-human primates, and may play a role in

  11. Oral administration of live Shigella vaccine candidates in rhesus monkeys show no evidence of competition for colonization and immunogenicity between different serotypes.

    PubMed

    Ranallo, R T; Kaminski, R; Baqar, S; Dutta, M; Lugo-Roman, L A; Boren, T; Barnoy, S; Venkatesan, M M

    2014-03-26

    Live oral monovalent Shigella flexneri 2a vaccine candidates as well as bivalent formulations with Shigella sonnei were evaluated in a rhesus monkey model for colonization and immunogenicity. Freshly harvested suspensions of S. flexneri 2a vaccine candidates WRSf2G12 and WRSf2G15 as well as S. sonnei vaccine candidate WRSs3 were nasogastrically administered to groups of rhesus monkeys, Macaca mulatta, either in a monovalent form or when combined with each other. The animals were monitored daily for physical well-being, stools were subjected to quantitative colony immunoblot assays for bacterial excretion and blood and stools were evaluated for humoral and mucosal immune responses. No clinical symptoms were noted in any group of animals and the vaccine candidates were excreted robustly for 48-72h without significant changes in either the magnitude or duration of excretion when given as a monovalent or as bivalent mixtures. Similarly, immunological interferences were not apparent in the magnitude of humoral and mucosal immune responses observed toward Shigella-specific antigens when monkeys were fed monovalent or bivalent formulations. These results predict that a multivalent live oral vaccine of more than one serotype can have a favorable outcome for protection against shigellosis. Published by Elsevier Ltd.

  12. Partial protection of SIV-infected rhesus monkeys against superinfection with a heterologous SIV isolate

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Korber, Bette

    2009-01-01

    Although there is increasing evidence that individuals already infected with human immunodeficiency virus type 1 (HIV-1) can be infected with a heterologous strain of the virus, the extent of protection against superinfection conferred by the first infection and the biologic consequences of superinfection are not well understood. We explored these questions in the simian immunodeficiency virus (SIV)/rhesus monkey model of HIV-1/AIDS. We infected cohorts of rhesus monkeys with either SIVmac251 or SIVsmE660 and then exposed animals to the reciprocal virus through intrarectal inoculations. Employing a quantitative real-time PCR assay, we determined the replication kinetics of the two strains of virusmore » for 20 weeks. We found that primary infection with a replication-competent virus did not protect against acquisition of infection by a heterologous virus but did confer relative control of the superinfecting virus. In animals that became superinfected, there was a reduction in peak replication and rapid control of the second virus. The relative susceptibility to superinfection was not correlated with CD4(+) T-cell count, CD4(+) memory T-cell subsets, cytokine production by virus-specific CD8(+) or CD4(+) cells, or neutralizing antibodies at the time of exposure to the second virus. Although there were transient increases in viral loads of the primary virus and a modest decline in CD4(+) T-cell counts after superinfection, there was no evidence of disease acceleration. These findings indicate that an immunodeficiency virus infection confers partial protection against a second immunodeficiency virus infection, but this protection may be mediated by mechanisms other than classical adaptive immune responses.« less

  13. A shift in energy metabolism anticipates the onset of sarcopenia in rhesus monkeys

    PubMed Central

    Pugh, Thomas D.; Conklin, Matthew W.; Evans, Trent D.; Polewski, Michael A.; Barbian, Hannah J.; Pass, Rachelle; Anderson, Bradley D.; Colman, Ricki J.; Eliceiri, Kevin W.; Keely, Patricia J.; Weindruch, Richard; Beasley, T. Mark; Anderson, Rozalyn M.

    2013-01-01

    Summary Age-associated skeletal muscle mass loss curtails quality of life and may contribute to defects in metabolic homeostasis in older persons. The onset of sarcopenia occurs in middle age in rhesus macaques although the trigger has yet to be identified. Here we show that a shift in metabolism occurs in advance of the onset of sarcopenia in rhesus vastus lateralis. Multiphoton laser scanning microscopy detects a shift in the kinetics of photon emission from autofluorescent metabolic cofactors NADH and FAD. Lifetime of both fluorophores is shortened at mid-age and this is observed in both free and bound constituent pools. Levels of FAD and free NADH are increased and the NAD/NADH redox ratio is lower. Concomitant with this, expression of fiber type myosin isoforms is altered resulting in a shift in fiber type distribution, activity of cytochrome c oxidase involved in mitochondrial oxidative phosphorylation is significantly lower, and the sub-cellular organization of mitochondria in oxidative fibers is compromised. A regulatory switch involving the transcriptional coactivator PGC-1α directs metabolic fuel utilization and governs the expression of structural proteins. Age did not significantly impact total levels of PGC-1α; however, its sub-cellular localization was disrupted, suggesting that PGC-1α activities may be compromised. Consistent with this, intracellular lipid storage is altered and there is shift to larger lipid droplet size that likely reflect a decline in lipid turnover or a loss in efficiency of lipid metabolism. We suggest that changes in energy metabolism contribute directly to skeletal muscle aging in rhesus monkeys. PMID:23607901

  14. Small particle aerosol inoculation of cowpox Brighton Red in rhesus monkeys results in a severe respiratory disease

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.

    Cowpox virus (CPXV) inoculation of nonhuman primates (NHPs) has been suggested as an alternate model for smallpox (Kramski et al., 2010, PLoS One, 5, e10412). Previously, we have demonstrated that intrabronchial inoculation of CPXV-Brighton Red (CPXV-BR) into cynomolgus monkeys resulted in a disease that shared many similarities to smallpox; however, severe respiratory tract disease was observed (Smith et al., 2011, J. Gen. Virol.). Here we describe the course of disease after small particle aerosol exposure of rhesus monkeys using computed tomography (CT) to monitor respiratory disease progression. Subjects developed a severe respiratory disease that was uniformly lethal at 5.7 log{submore » 10} PFU of CPXV-BR. CT indicated changes in lung architecture that correlated with changes in peripheral blood monocytes and peripheral oxygen saturation. While the small particle aerosol inoculation route does not accurately mimic human smallpox, the data suggest that CT can be used as a tool to monitor real-time disease progression for evaluation of animal models for human diseases. - Highlights: • Small particle aerosol exposure of rhesus results in a severe respiratory disease. • CT findings correlated with peripheral oxygen saturation and monocyte increases. • Virus dissemination was limited and mainly confined to the respiratory tract. • CT provides insight into pathogenesis to aid development of animal models of disease.« less

  15. What Meaning Means for Same and Different: Analogical Reasoning in Humans (Homo sapiens), Chimpanzees (Pan troglodytes), and Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Flemming, Timothy M.; Beran, Michael J.; Thompson, Roger K. R.; Kleider, Heather M.; Washburn, David A.

    2013-01-01

    Thus far, language- and token-trained apes (e.g., D. Premack, 1976; R. K. R. Thompson, D. L. Oden, & S. T. Boysen, 1997) have provided the best evidence that nonhuman animals can solve, complete, and construct analogies, thus implicating symbolic representation as the mechanism enabling the phenomenon. In this study, the authors examined the role of stimulus meaning in the analogical reasoning abilities of three different primate species. Humans (Homo sapiens), chimpanzees (Pan troglodytes), and rhesus monkeys (Macaca mulatta) completed the same relational matching-to-sample (RMTS) tasks with both meaningful and nonmeaningful stimuli. This discrimination of relations-between-relations serves as the basis for analogical reasoning. Meaningfulness facilitated the acquisition of analogical matching for human participants, whereas individual differences among the chimpanzees suggest that meaning can either enable or hinder their ability to complete analogies. Rhesus monkeys did not succeed in the RMTS task regardless of stimulus meaning, suggesting that their ability to reason analogically, if present at all, may be dependent on a dimension other than the representational value of stimuli. PMID:18489233

  16. Upregulation of Aβ42 in the Brain and Bodily Fluids of Rhesus Monkeys with Aging.

    PubMed

    Zhao, Qiao; Lu, Jing; Yao, Zitong; Wang, Shubo; Zhu, Liming; Wang, Ju; Chen, Baian

    2017-01-01

    The cerebral accumulation of amyloid beta (Aβ) is one of the key pathological hallmarks of Alzheimer's disease (AD). Aβ is also found in bodily fluids such as the cerebrospinal fluid (CSF) and plasma. However, the significance of Aβ accumulation in the brain and different bodily pools, as well as its correlation with aging and cerebral amyloid pathology, is not completely understood. To better understand this question, we selected the rhesus monkey, which is phylogenetically and physiologically highly similar to the human, as a model to study. We quantified the levels of the two main Aβ isoforms (Aβ42 and Aβ40) in different sections of the brain (frontal cortex, temporal cortex, and hippocampus) and bodily fluids (CSF and plasma) of rhesus monkeys at different developmental phases (young, 5-9 years of age; mature, 10-19 years of age; and old, 21-24 years of age). We found that the levels of neuronal and insoluble Aβ42 increased significantly in the brain with aging, suggesting that this specific isoform might be directly involved in aging and AD-like pathophysiology. There was no significant change in the Aβ40 level in the brain with aging. In addition, the Aβ42 level, but not the Aβ40 level, in both the CSF and plasma increased with aging. We also identified a positive correlation between Aβ42 in the CSF and plasma and Aβ42 in the brain. Taken collectively, our results indicate that there is an association between Aβ accumulation and age. These results support the increased incidence of AD with aging.

  17. A Rhesus Monkey Model of Self Injury: Effects of Relocation Stress on Behavior and Neuroendocrine Function

    PubMed Central

    Davenport, Matthew D.; Lutz, Corrine K.; Tiefenbacher, Stefan; Novak, Melinda A.; Meyer, Jerrold S.

    2008-01-01

    Background Self-injurious behavior (SIB), a disorder that afflicts many individuals within both clinical and non-clinical populations, has been linked to states of heightened stress and arousal. However, there are no published longitudinal data on the relationship between increases in stress and changes in the incidence of SIB. The present study investigated the short- and long-term behavioral and neuroendocrine responses of SIB and control monkeys to the stress of relocation. Methods Twenty adult male rhesus macaques were exposed to the stress of relocation to a new housing arrangement in a newly constructed facility. Daytime behavior, sleep, and multiple measures of hypothalamic-pituitary-adrenocortical (HPA) axis function were investigated before and after the move. Results Relocation induced a complex pattern of short- and long-term effects in the animals. The SIB animals showed a long-lasting increase in self-biting behavior as well as evidence of sleep disturbance. Both groups exhibited elevated cortisol levels in saliva, serum, and hair, and also an unexpected delayed increase in circulating concentrations of corticosteroid binding globulin (CBG). Conclusions Our results indicate that relocation is a significant stressor for rhesus macaques, and that this stressor triggers an increase in self-biting behavior as well as sleep disturbance in monkeys previously identified as suffering from SIB. These findings suggest that life stresses may similarly exacerbate SIB in humans with this disorder. The HPA axis results underscore the potential role of CBG in regulating long-term neuroendocrine responses to major stressors. PMID:18164279

  18. Niche partitioning between sympatric rhesus macaques and Yunnan snub-nosed monkeys at Baimaxueshan Nature Reserve, China.

    PubMed

    Grueter, Cyril C; Li, Da-Yong; Feng, Shun-Kai; Ren, Bao-Ping

    2010-10-01

    Here we provide a preliminary assessment of dietary and habitat requirements of two sympatric primate taxa, a "simple-stomached" and "complex-stomached" species (Rhinopithecus bieti Colobinae vs. Macaca mulatta Cercopithecinae), as a basis for illuminating how the two coexist. Of ca. 22 plant food species consumed by the macaques, at least 16 were also eaten by the snub-nosed monkeys. Both species showed a preference for fruits. While the snub-nosed monkeys did not utilize any resources associated with human communities, rhesus macaques did occasionally raid agricultural crops. The mean elevation of the snub-nosed monkey group was 3,218 m, while the mean elevation of the macaque group was 2,995 m. Macaques were also spotted on meadows whereas snub-nosed monkeys evidently avoided these. For both species, mixed deciduous broadleaf/conifer forest was the most frequently used ecotype, but whereas evergreen broadleaf forest (Cyclobalanopsis community) accounted for only 3% of the location records of the snub-nosed monkeys, it accounted for 36% of the location records of the macaques. Groups of the two species usually kept a considerable spatial distance from one another (mean 2.4 km). One close encounter and confrontation between groups of the two species resulted in the macaque group moving away. Our findings suggest that the coexistence of the two taxa is facilitated via differential macrohabitat use and spatial avoidance. Although divergent habitat-use strategies may reflect interspecific competition, they may also merely reflect different physiological or ecological requirements.

  19. Effect of hypoxia by intermittent altitude exposure on semen characteristics and testicular morphology of male rhesus monkeys

    NASA Astrophysics Data System (ADS)

    Saxena, D. K.

    1995-09-01

    Semen characteristics and testicular morphology of rhesus monkeys were studied on exposure to a simulated high altitude of 4411 m for 21 days. There was a partially reversible decrease in the semen volume, sperm count and sperm motility, as well as an elevation of pH and fructose concentration. These changes were associated with degeneration of the germinal epithelium and spermatogenic arrest at the end of third week of exposure which had not recovered even 3 weeks after the exposure.

  20. Computer-task testing of rhesus monkeys (Macaca mulatta) in the social milieu.

    PubMed

    Washburn, D A; Harper, S; Rumbaugh, D M

    1994-07-01

    Previous research has demonstrated that a behavior and performance testing paradigm, in which rhesus monkeys (Macaca mulatta) manipulate a joystick to respond to computer-generated stimuli, provides environmental enrichment and supports the psychological well-being of captive research animals. The present study was designed to determine whether computer-task activity would be affected by pair-housing animals that had previously been tested only in their single-animal home cages. No differences were observed in productivity or performance levels as a function of housing condition, even when the animals were required to "self-identify" prior to performing each trial. The data indicate that cognitive challenge and control are as preferred by the animals as social opportunities, and that, together with comfort/health considerations, each must be addressed for the assurance of psychological well-being.

  1. Ranking Cognitive Flexibility in a Group Setting of Rhesus Monkeys with a Set-Shifting Procedure.

    PubMed

    Shnitko, Tatiana A; Allen, Daicia C; Gonzales, Steven W; Walter, Nicole A R; Grant, Kathleen A

    2017-01-01

    Attentional set-shifting ability is an executive function underling cognitive flexibility in humans and animals. In humans, this function is typically observed during a single experimental session where dimensions of playing cards are used to measure flexibility in the face of changing rules for reinforcement (i.e., the Wisconsin Card Sorting Test (WCST)). In laboratory animals, particularly non-human primates, variants of the WCST involve extensive training and testing on a series of dimensional discriminations, usually in social isolation. In the present study, a novel experimental approach was used to assess attentional set-shifting simultaneously in 12 rhesus monkeys. Specifically, monkeys living in individual cages but in the same room were trained at the same time each day in a set-shifting task in the same housing environment. As opposed to the previous studies, each daily session began with a simple single-dimension discrimination regardless of the animal's performance on the previous session. A total of eight increasingly difficult, discriminations (sets) were possible in each daily 45 min session. Correct responses were reinforced under a second-order schedule of flavored food pellet delivery, and criteria for completing a set was 12 correct trials out of a running total of 15 trials. Monkeys progressed through the sets at their own pace and abilities. The results demonstrate that all 12 monkeys acquired the simple discrimination (the first set), but individual differences in the ability to progress through all eight sets were apparent. A performance index (PI) that encompassed progression through the sets, errors and session duration was calculated and used to rank each monkey's performance in relation to each other. Overall, this version of a set-shifting task results in an efficient assessment of reliable differences in cognitive flexibility in a group of monkeys.

  2. Role of d-amphetamine and d-methamphetamine as active metabolites of benzphetamine: Evidence from drug discrimination and pharmacokinetic studies in male rhesus monkeys.

    PubMed

    Banks, Matthew L; Snyder, Rodney W; Fennell, Timothy R; Negus, S Stevens

    2017-05-01

    Benzphetamine is a Schedule III anorectic agent that is a prodrug for d-amphetamine and d-methamphetamine and may have utility as an "agonist" medication for cocaine use disorder treatment. This study evaluated the pharmacokinetic-pharmacodynamic profile of benzphetamine using a drug discrimination procedure in rhesus monkeys. The potency and time course of cocaine-like discriminative stimulus effects were compared for benzphetamine (10-18mg/kg, intramuscular (IM)) and d-amphetamine (0.032-0.32mg/kg, IM) in monkeys (n=3-4) trained to discriminate IM cocaine (0.32mg/kg) from saline in a two-key food-reinforced discrimination procedure. Parallel pharmacokinetic studies in the same monkeys determined plasma benzphetamine, d-methamphetamine and/or d-amphetamine levels for correlation with behavioral effects. d-Amphetamine produced dose-dependent, time-dependent, and full cocaine-like effects, i.e. ≥90% cocaine-appropriate responding, in all monkeys without altering response rates. The time course of d-amphetamine's cocaine-like discriminative stimulus effects correlated with plasma d-amphetamine levels. Benzphetamine was 180-fold less potent than d-amphetamine and produced full cocaine-like effects in only 2 of 4 monkeys while significantly decreasing response rates. Benzphetamine administration increased plasma d-methamphetamine (peak at 100min) and d-amphetamine (peak at 24h) levels, but the time course of behavioral effects did not correlate with increased levels of benzphetamine, d-methamphetamine or d-amphetamine. These results suggest that benzphetamine yields d-amphetamine and d-methamphetamine as active metabolites in rhesus monkeys, but generation of these metabolites is not sufficient to account for benzphetamine behavioral effects. The incomplete cocaine substitution profile and protracted d-amphetamine plasma levels suggest that benzphetamine may still warrant further evaluation as a candidate pharmacotherapy for cocaine use disorder treatment. Copyright

  3. Role of d-amphetamine and d-methamphetamine as active metabolites of benzphetamine: evidence from drug discrimination and pharmacokinetic studies in male rhesus monkeys

    PubMed Central

    Banks, Matthew L.; Snyder, Rodney W.; Fennell, Timothy R.; Negus, S. Stevens

    2017-01-01

    Benzphetamine is a Schedule III anorectic agent that is a prodrug for d-amphetamine and d-methamphetamine and may have utility as an “agonist” medication for cocaine use disorder treatment. This study evaluated the pharmacokinetic-pharmacodynamic profile of benzphetamine using a drug discrimination procedure in rhesus monkeys. The potency and time course of cocaine-like discriminative stimulus effects were compared for benzphetamine (10–18 mg/kg, intramuscular (IM)) and d-amphetamine (0.032–0.32 mg/kg, IM) in monkeys (n=3–4) trained to discriminate IM cocaine (0.32 mg/kg) from saline in a two-key food-reinforced discrimination procedure. Parallel pharmacokinetic studies in the same monkeys determined plasma benzphetamine, d-methamphetamine and/or d-amphetamine levels for correlation with behavioral effects. d-Amphetamine produced dose-dependent, time-dependent, and full cocaine-like effects, i.e. ≥ 90% cocaine-appropriate responding,in all monkeys without altering response rates. The time course of d-amphetamine’s cocaine-like discriminative stimulus effects correlated with plasma d-amphetamine levels. Benzphetamine was 180-fold less potent than d-amphetamine and produced full cocaine-like effects in only 2 of 4 monkeys while significantly decreasing response rates. Benzphetamine administration increased plasma d-methamphetamine (peak at 100 min) and d-amphetamine (peak at 24 h) levels, but the time course of behavioral effects did not correlate with increased levels of benzphetamine, d-methamphetamine or d-amphetamine. These results suggest that benzphetamine yields d-amphetamine and d-methamphetamine as active metabolites in rhesus monkeys, but generation of these metabolites is not sufficient to account for benzphetamine behavioral effects. The incomplete cocaine substitution profile and protracted d-amphetamine plasma levels suggest that benzphetamine may still warrant further evaluation as a candidate pharmacotherapy for cocaine use disorder

  4. Effects of chronic binge-like ethanol consumption on cocaine self-administration in rhesus monkeys.

    PubMed

    Czoty, Paul W

    2015-08-01

    Most cocaine abusers also abuse alcohol, but little is known about interactions that promote co-abuse. These experiments in rhesus monkeys determined the effects of >8 weeks of ethanol (EtOH) consumption on cocaine self-administration (n=6), effects of dopamine (DA) receptor antagonists on cocaine reinforcement (n=3-4 per drug) and the ability of the D2-like DA receptor agonist quinpirole to elicit yawning (n=3). Monkeys self-administered cocaine (0.0-1.0mg/kg/injection, i.v.) under a 300-s fixed-interval schedule and the above-listed variables were measured before EtOH exposure. Next, monkeys consumed a sweetened, 4% EtOH solution in the home cage under binge-like conditions: 1h, 5 days/week with daily intake equaling 2.0g/kg EtOH. After approximately 8 weeks, measures were re-determined, then EtOH drinking was discontinued. Finally, acute effects of EtOH on cocaine self-administration were determined by infusing EtOH (0.0-1.0g/kg. i.v.) prior to cocaine self-administration sessions (n=4). In five of six monkeys, EtOH drinking increased self-administration of low cocaine doses but did not alter reinforcing effects of higher doses. Self-administration returned to baseline after EtOH access was terminated (n=3). Effects of DA receptor antagonists on cocaine self-administration were not consistently altered after EtOH consumption, but the ability of quinpirole to induce yawning was enhanced in two of three monkeys. Acute EtOH infusions only decreased self-administration of lower cocaine doses. Taken together, the data suggest that long-term EtOH exposure can increase sensitivity to cocaine, possibly by increasing D3 receptor sensitivity. Data do not support a role for acute pharmacological interactions in promoting cocaine/EtOH co-abuse. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Relationship between discriminative stimulus effects and plasma methamphetamine and amphetamine levels of intramuscular methamphetamine in male rhesus monkeys.

    PubMed

    Banks, Matthew L; Smith, Douglas A; Kisor, David F; Poklis, Justin L

    2016-02-01

    Methamphetamine is a globally abused drug that is metabolized to amphetamine, which also produces abuse-related behavioral effects. However, the contributing role of methamphetamine metabolism to amphetamine in methamphetamine's abuse-related subjective effects is unknown. This preclinical study was designed to determine 1) the relationship between plasma methamphetamine levels and methamphetamine discriminative stimulus effects and 2) the contribution of the methamphetamine metabolite amphetamine in the discriminative stimulus effects of methamphetamine in rhesus monkeys. Adult male rhesus monkeys (n=3) were trained to discriminate 0.18mg/kg intramuscular (+)-methamphetamine from saline in a two-key food-reinforced discrimination procedure. Time course of saline, (+)-methamphetamine (0.032-0.32mg/kg), and (+)-amphetamine (0.032-0.32mg/kg) discriminative stimulus effects were determined. Parallel pharmacokinetic studies were conducted in the same monkeys to determine plasma methamphetamine and amphetamine levels after methamphetamine administration and amphetamine levels after amphetamine administration for correlation with behavior in the discrimination procedure. Both methamphetamine and amphetamine produced full, ≥90%, methamphetamine-like discriminative stimulus effects. Amphetamine displayed a slightly, but significantly, longer duration of action than methamphetamine in the discrimination procedure. Both methamphetamine and amphetamine behavioral effects were related to methamphetamine and amphetamine plasma levels by a clockwise hysteresis loop indicating acute tolerance had developed to the discriminative stimulus effects. Furthermore, amphetamine levels after methamphetamine administration were absent when methamphetamine stimulus effects were greatest and peaked when methamphetamine discriminative stimulus effects returned to saline-like levels. Overall, these results demonstrate the methamphetamine metabolite amphetamine does not contribute to

  6. An Entamoeba sp. strain isolated from rhesus monkey is virulent but genetically different from Entamoeba histolytica.

    PubMed

    Tachibana, Hiroshi; Yanagi, Tetsuo; Pandey, Kishor; Cheng, Xun-Jia; Kobayashi, Seiki; Sherchand, Jeevan B; Kanbara, Hiroji

    2007-06-01

    An Entamoeba sp. strain, P19-061405, was isolated from a rhesus monkey in Nepal and characterized genetically. The strain was initially identified as Entamoeba histolytica using PCR amplification of peroxiredoxin genes. However, sequence analysis of the 18S rRNA gene showed a 0.8% difference when compared to the reference E. histolytica HM-1:IMSS human strain. Differences were also observed in the 5.8S rRNA gene and the internal transcribed spacer (ITS) regions 1 and 2, and analysis of the serine-rich protein gene from the monkey strain showed unique codon usages compared to E. histolytica isolated from humans. The amino acid sequences of two hexokinases and two glucose phosphate isomerases also differed from those of E. histolytica. Isoenzyme analyses of these enzymes in the monkey strain showed different electrophoretic mobility patterns compared with E. histolytica isolates. Analysis of peroxiredoxin genes indicated the presence of at least seven different types of protein, none of which were identical to proteins in E. histolytica. When the trophozoites from the monkey strain were inoculated into the livers of hamsters, formation of amebic abscesses was observed 7 days after the injection. These results demonstrate that the strain is genetically different from E. histolytica and is virulent. Revival of the name Entamoeba nuttalli is proposed for the organism.

  7. Otoacoustic emissions measured in rhesus monkeys (Macaca mulatta)

    NASA Astrophysics Data System (ADS)

    McFadden, Dennis; Pasanen, Edward G.; Raper, Jessica; Wallen, Kim

    2003-10-01

    In humans, otoacoustic emissions (OAEs) are stronger in females than in males and stronger in right ears than in left. The physiological bases for these differences are unknown, but several lines of circumstantial evidence suggest that the sex difference is attributable to androgenizing mechanisms operating during prenatal development. Specifically, it appears that exposure to high levels of androgens during prenatal development diminishes the strength of the cochlear amplifiers and thus the strength of the OAEs. Sex and ear differences in OAEs have not been well studied in species other than humans. Accordingly, click-evoked OAEs and distortion-product OAEs were measured in nine female and nine male rhesus monkeys. For CEOAEs, but less clearly for DPOAEs, females exhibited significantly stronger OAEs than males. There was no consistent ear difference for either sex for either type of OAE. In order to better study the early components of the CEOAE waveform, a nonlinear procedure [Molenaar et al., Hearing Res. 143, 197-207 (2002)] was used to collect CEOAEs along with our standard (linear) procedure. This colony also contains animals of each sex that were treated with androgenic or antiandrogenic agents during prenatal development, and OAEs are also currently being measured on those animals. [Work supported by NIDCD.

  8. Induction of Encephalitis in Rhesus Monkeys Infused with Lymphocryptovirus-Infected B-Cells Presenting MOG34–56 Peptide

    PubMed Central

    Haanstra, Krista G.; Wubben, Jacqueline A. M.; Jonker, Margreet; Hart, Bert A. ‘t.

    2013-01-01

    The overlapping epidemiology of multiple sclerosis (MS) and Epstein-Barr virus (EBV), the increased risk to develop MS after infectious mononucleosis (IM) and the localization of EBV-infected B-cells within the MS brain suggest a causal link between EBV and MS. However, the underlying mechanism is unknown. We hypothesize that EBV-infected B-cells are capable of eliciting a central nervous system (CNS) targeting autoimmune reaction. To test this hypothesis we have developed a novel experimental model in rhesus monkeys of IM-like disease induced by infusing autologous B-lymphoblastoid cells (B-LCL). Herpesvirus papio (HVP) is a lymphocryptovirus related to EBV and was used to generate rhesus monkey B-LCL. Three groups of five animals were included; each group received three intravenous infusions of B-LCL that were either pulsed with the encephalitogenic self peptide MOG34–56 (group A), a mimicry peptide (981–1003) of the major capsid protein of cytomegalovirus (CMVmcp981–1003; group B) or the citrullinated MOG34–56 (cMOG34–56; group C). Groups A and B received on day 98 a single immunization with MOG34–56 in incomplete Freund’s adjuvant (IFA). Group C monkeys were euthanized just prior to day 98 without booster immunization. We observed self-peptide-specific proliferation of T-cells, superimposed on similar strong proliferation of CD3+CD8+ T-cells against the B-LCL as observed in IM. The brains of several monkeys contained perivascular inflammatory lesions of variable size, comprising CD3+ and CD68+ cells. Moreover, clusters of CD3+ and CD20+ cells were detected in the meninges. The only evident clinical sign was substantial loss of bodyweight (>15%), a symptom observed both in early autoimmune encephalitis and IM. In conclusion, this model suggests that EBV-induced B-LCL can elicit a CNS targeting inflammatory (auto)immune reaction. PMID:23977076

  9. In vivo distribution of carbon-11 phenytoin and its major metabolite, and their use in scintigraphic imaging. [Rhesus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Stavchansky, S.A.; Tilbury, R.S.; McDonald, J.M.

    1978-08-01

    Curie quantities (0.3 to 1.5 Ci) of H/sup 11/CN were used in the synthesis of C-11-tagged phenytoin (C-11.DPH) and 5-(p-hydroxyphenyl)-5-phenylhydantoin (C-11.HPPH), using a modified Buecherer--Bergs reaction. The H/sup 11/CN was produced from a mixture of 95% nitrogen and 5% hydrogen by a 45-min bombardment with 10-MeV protons at 10 ..mu..A. Following iv infusions of C-11 DPH (13.7 mg/kg at a rate of 29 mg/min) into the left femoral vein of Rhesus monkeys, DPH shows persistent concentration in the brain and liver fields. Extravascular administration shows significant retention at the site of administration. Intravenous bolus injection of (/sup 11/C)-HPPH into amore » Rhesus monkey, at a dose of 6.4 mg/kg, resulted in localization of this compound in the liver, gallbladder, urinary bladder, and intestinal fields. Loss of activity from the liver region, with appearance of this activity in the intestinal field, suggests that (/sup 11/C)-HPPH is secreted into the intestine via the bile. Further investigation is needed to study the potential of (/sup 11/C)-DPH as a brain-scanning agent and (/sup 11/C)-HPPH as a possible cholescintigraphic agent.« less

  10. Effects of testosterone on attention and memory for emotional stimuli in male rhesus monkeys.

    PubMed

    King, Hanna M; Kurdziel, Laura B; Meyer, Jerrold S; Lacreuse, Agnès

    2012-03-01

    Increasing evidence in humans and other animals suggests that testosterone (T) plays an important role in modulating emotion. We previously reported that T treatment in rhesus monkeys undergoing chemically induced hypogonadism results in increased watching time of videos depicting fights between unfamiliar conspecifics (Lacreuse et al., 2010). In the current study, we aimed to further investigate the effect of T manipulations on attention and memory for emotional stimuli in male rhesus monkeys. Six males (7 years old) were administered Depot Lupron to suppress endogenous T levels and treated with either testosterone enanthate (TE, 5 mg/kg) or oil, before crossing over to the alternate treatment. Animals were tested for 16 weeks on two computerized touchscreen tasks with both social and nonsocial emotional and neutral stimuli. The Dot-Probe task was used to measure attention, and the Delayed-Non-Matching-to-Sample task with a 1s delay (DNMS) was used to measure recognition memory for these stimuli. Performance on the two tasks was examined during each of four month-long phases: Baseline, Lupron alone, Lupron+TE and Lupron+oil. It was predicted that T administration would lead to increased attention to negative social stimuli (i.e., negative facial expressions of unfamiliar conspecifics) and would improve memory for such stimuli. We found no evidence to support these predictions. In the Dot-Probe task, an attentional bias towards negative social stimuli was observed at baseline, but T treatment did not enhance this bias. Instead, monkeys had faster response times when treated with T compared to oil, independently of the emotional valence or social relevance of stimuli, perhaps reflecting an enhancing effect of T on reward sensitivity or general arousal. In the DNMS, animals had better memory for nonsocial compared to social stimuli and showed the poorest performance in the recognition of positive facial expressions. However, T did not affect performance on the task

  11. Effects of continuous nicotine treatment and subsequent termination on cocaine vs. food choice in male rhesus monkeys

    PubMed Central

    Schwienteck, Kathryn L.; Negus, S. Stevens; Poklis, Justin L.; Banks, Matthew L.

    2015-01-01

    One complicating factor in cocaine addiction may be concurrent exposure and potential dependence on nicotine. The aim of the present study was to determine the effects of continuous nicotine treatment and subsequent termination on cocaine vs. food choice in rhesus monkeys. For comparison, we also determined effects of the nicotinic receptor antagonist mecamylamine on cocaine vs. food choice during continuous saline and nicotine treatment. Rhesus monkeys (n=3) responded under a concurrent schedule of food pellet (1g) and intravenous cocaine (0 – 0.1 mg/kg/injection) availability. Saline and ascending nicotine doses (0.1 – 1.0 mg/kg/h, IV) were continuously infused for 7-day treatment periods and separated by 24 h saline treatment periods. Acute effects of mecamylamine (0.32 – 1.8 mg/kg, IM, 15 min pretreatment) were determined during continuous saline and 0.32 mg/kg/h nicotine treatments. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice. Nicotine treatment did not alter cocaine vs. food choice. In contrast, preference of 0.032 mg/kg/injection cocaine was attenuated 24 h following termination of 0.32 mg/kg/h nicotine treatment despite no somatic abstinence signs being observed. Acute mecamylamine enhanced cocaine choice during saline treatment and mainly suppressed rates of behavior during nicotine treatment. Overall, continuous nicotine exposure, up to 1 mg/kg/h, does not enhance cocaine choice and does not produce nicotine dependence as demonstrated by the lack of abstinence signs. PMID:26098473

  12. Airway epithelial wounds in rhesus monkey generate ionic currents that guide cell migration to promote healing

    PubMed Central

    Sun, Yao-Hui; Reid, Brian; Fontaine, Justin H.; Miller, Lisa A.; Hyde, Dallas M.; Mogilner, Alex

    2011-01-01

    Damage to the respiratory epithelium is one of the most critical steps to many life-threatening diseases, such as acute respiratory distress syndrome and chronic obstructive pulmonary disease. The mechanisms underlying repair of the damaged epithelium have not yet been fully elucidated. Here we provide experimental evidence suggesting a novel mechanism for wound repair: endogenous electric currents. It is known that the airway epithelium maintains a voltage difference referred to as the transepithelial potential. Using a noninvasive vibrating probe, we demonstrate that wounds in the epithelium of trachea from rhesus monkeys generate significant outward electric currents. A small slit wound produced an outward current (1.59 μA/cm2), which could be enhanced (nearly doubled) by the ion transport stimulator aminophylline. In addition, inhibiting cystic fibrosis transmembrane conductance regulator (CFTR) with CFTR(Inh)-172 significantly reduced wound currents (0.17 μA/cm2), implicating an important role of ion transporters in wound induced electric potentials. Time-lapse video microscopy showed that applied electric fields (EFs) induced robust directional migration of primary tracheobronchial epithelial cells from rhesus monkeys, towards the cathode, with a threshold of <23 mV/mm. Reversal of the field polarity induced cell migration towards the new cathode. We further demonstrate that application of an EF promoted wound healing in a monolayer wound healing assay. Our results suggest that endogenous electric currents at sites of tracheal epithelial injury may direct cell migration, which could benefit restitution of damaged airway mucosa. Manipulation of ion transport may lead to novel therapeutic approaches to repair damaged respiratory epithelium. PMID:21719726

  13. Endocrine antecedents of polycystic ovary syndrome (PCOS) in fetal and infant prenatally androgenized female rhesus monkeys

    PubMed Central

    Abbott, David H; Barnett, Deborah K; Levine, Jon E; Padmanabhan, Vasantha; Dumesic, Daniel A; Jacoris, Steve; Tarantal, Alice F

    2008-01-01

    Experimentally induced fetal androgen excess induces polycystic ovary syndrome (PCOS)-like traits in adult female rhesus monkeys. Developmental changes leading to this endocrinopathy are not known. We therefore studied 15 time-mated, gravid female rhesus monkeys with known female fetuses. Nine dams received daily subcutaneous injections of 15 mg testosterone propionate (TP) and six received injections of oil vehicle (controls) from 40 through 80 days of gestation (term 165 [range: ±10] days), and all fetuses were delivered by Cesarean-section using established methods at term. Ultrasound-guided fetal blood sample collection and peripheral venous sample collection of dams and subsequent infants enabled determination of circulating levels of steroid hormones, LH and FSH. TP injections elevated serum testosterone and androstenedione levels in the dams and prenatally androgenized (PA) fetuses. After cessation of TP injections, testosterone levels mostly normalized, while serum androstenedione levels in PA infants were elevated. TP injections did not increase estrogen levels in the dams, PA fetuses and infants, yet conjugated estrogen levels were elevated in the TP-injected dams. Serum levels of LH and FSH were elevated in late gestation PA fetuses, and LH levels were elevated in PA infants. These studies suggest that experimentally-induced fetal androgen excess increases gonadotropin secretion in PA female fetuses and infants, and elevates endogenous androgen levels in PA infants. Thus, in this nonhuman primate model, differential programming of the fetal hypothalamo-pituitary unit with concomitant hyperandrogenism provides evidence to suggest developmental origins of LH and androgen excess in adulthood. PMID:18385445

  14. Concurrent determination of bisphenol A pharmacokinetics in maternal and fetal rhesus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Patterson, Tucker A.; Twaddle, Nathan C.; Roegge, Cindy S.

    Bisphenol A (BPA) is an important industrial chemical used as the monomer for polycarbonate plastic and in epoxy resins for food can liners. Worldwide biomonitoring studies consistently find a high prevalence of BPA conjugates in urine (> 90%) in amounts consistent with aggregate exposure at levels below 1 μg/kg bw/d. The current study used LC/MS/MS to measure concurrently the pharmacokinetics of aglycone (active) and conjugated (inactive) deuterated BPA (d6) in maternal and fetal rhesus monkey serum, amniotic fluid, and placenta following intravenous injection in the dam (100 μg/kg bw). Internal exposures of the fetus to aglycone d6-BPA (serum AUC) weremore » attenuated by maternal, placental, and fetal Phase II metabolism to less than half that in the dam. Levels of aglycone and conjugated d6-BPA measured in whole placenta were consistent with a role in metabolic detoxification. The monotonic elimination of aglycone d6-BPA from the fetal compartment accompanied by persistent conjugate levels provides further evidence arguing against the hypothesis that BPA conjugates are selectively deconjugated by either the placenta or fetus. These results also provide benchmarks to guide the interpretation of human cord blood, amniotic fluid, and placenta sampling and measurement strategies as a basis for estimating fetal exposures to BPA. This study in a non-human primate model provides additional pharmacokinetic data for use in PBPK modeling of perinatal exposures to BPA from food contact, medical devices, and other environmental sources. - Highlights: ► Maternal, placental, and fetal Phase II metabolism attenuate fetal exposure to BPA. ► Serum AUC for aglycone BPA in fetal monkeys is less than half of that in the dam. ► BPA profiles in monkey fetus rule out selective deconjugation and accumulation. ► BPA levels in monkey placenta are similar to other metabolically active tissues. ► Some published human cord blood data for BPA are inconsistent with these

  15. Low Lactobacilli abundance and polymicrobial diversity in the lower reproductive tract of female rhesus monkeys do not compromise their reproductive success.

    PubMed

    Amaral, Wellington Z; Lubach, Gabriele R; Kapoor, Amita; Proctor, Alexandra; Phillips, Gregory J; Lyte, Mark; Coe, Christopher L

    2017-10-01

    The lower reproductive tract of nonhuman primates is colonized with a diverse microbiota, resembling bacterial vaginosis (BV), a gynecological condition associated with negative reproductive outcomes in women. Our 4 aims were to: (i) assess the prevalence of low Lactobacilli and a BV-like profile in female rhesus monkeys; (ii) quantify cytokines in their cervicovaginal fluid (CVF); (iii) examine the composition and structure of their mucosal microbiota with culture-independent sequencing methods; and (iv) evaluate the potential influence on reproductive success. CVF specimens were obtained from 27 female rhesus monkeys for Gram's staining, and to determine acidity (pH), and quantify proinflammatory cytokines. Based on Nugent's classification, 40% had a score of 7 or higher, which would be indicative of BV in women. Nugent scores were significantly correlated with the pH of the CVF. Interleukin-1ß was present at high concentrations, but not further elevated by high Nugent scores. Vaginal swabs were obtained from eight additional females to determine microbial diversity by rRNA gene amplicon sequencing. At the phylum level, the Firmicutes/Bacteroidetes ratio was low. The relative abundance of Lactobacilli was also low (between 3% and 17%), and 11 other genera were present at >1%. However, neither the microbial diversity in the community structure, nor high Nugent scores, was associated with reduced fecundity. Female monkeys provide an opportunity to understand how reproductive success can be sustained in the presence of a diverse polymicrobial community in the reproductive tract. © 2017 Wiley Periodicals, Inc.

  16. Monochromatic ocular wave aberrations in young monkeys

    PubMed Central

    Ramamirtham, Ramkumar; Kee, Chea-su; Hung, Li-Fang; Qiao-Grider, Ying; Roorda, Austin; Smith, Earl L.

    2006-01-01

    High-order monochromatic aberrations could potentially influence vision-dependent refractive development in a variety of ways. As a first step in understanding the effects of wave aberration on refractive development, we characterized the maturational changes that take place in the high-order aberrations of infant rhesus monkey eyes. Specifically, we compared the monochromatic wave aberrations of infant and adolescent animals and measured the longitudinal changes in the high-order aberrations of infant monkeys during the early period when emmetropization takes place. Our main findings were that (1) adolescent monkey eyes have excellent optical quality, exhibiting total RMS errors that were slightly better than those for adult human eyes that have the same numerical aperture and (2) shortly after birth, infant rhesus monkeys exhibited relatively larger magnitudes of high-order aberrations predominately spherical aberration, coma, and trefoil, which decreased rapidly to assume adolescent values by about 200 days of age. The results demonstrate that rhesus monkey eyes are a good model for studying the contribution of individual ocular components to the eye’s overall aberration structure, the mechanisms responsible for the improvements in optical quality that occur during early ocular development, and the effects of high-order aberrations on ocular growth and emmetropization. PMID:16750549

  17. Simian virus 40 inhibits differentiation and maturation of rhesus macaque DC-SIGN(+) dendritic cells.

    PubMed

    Changyong, C; Sun, M; Li, H; Brockmeyer, N; Wu, Nan Ping

    2010-09-24

    Dendritic cells (DC) are the initiators and modulators of the immune responses. Some species of pathogenic microorganisms have developed immune evasion strategies by controlling antigen presentation function of DC. Simian virus 40 (SV40) is a DNA tumor virus of rhesus monkey origin. It can induce cell transformation and tumorigenesis in many vertebrate species, but often causes no visible effects and persists as a latent infection in rhesus monkeys under natural conditions. To investigate the interaction between SV40 and rhesus monkey DC, rhesus monkey peripheral blood monocyte-derived DC were induced using recombinant human Interleukin-4 (rhIL-4) and infective SV40, the phenotype and function of DC-specific intracellular adhesion molecule-3 grabbing nonintegrin (DC-SIGN)(+) DC were analyzed by flow cytometry (FCM) and mixed lymphocyte reaction (MLR). Results showed that SV40 can down-regulate the expression of CD83 and CD86 on DC and impair DC-induced activation of T cell proliferation. These findings suggest that SV40 might also cause immune suppression by influencing differentiation and maturation of DC.

  18. Changes in food intake and abnormal behavior using a puzzle feeder in newly acquired sub-adult rhesus monkeys (Macaca mulatta): a short term study.

    PubMed

    Lee, Jae-Il; Lee, Chi-Woo; Kwon, Hyouk-Sang; Kim, Young-Tae; Park, Chung-Gyu; Kim, Sang-Joon; Kang, Byeong-Cheol

    2008-10-01

    The majority of newly acquired nonhuman primates encounter serious problems adapting themselves to new environments or facilities. In particular, loss of appetite and abnormal behavior can occur in response to environmental stresses. These adaptation abnormalities can ultimately have an affect on the animal's growth and well-being. In this study, we evaluated the affects of a puzzle feeder on the food intake and abnormal behavior of newly acquired rhesus monkeys for a short period. The puzzle feeder was applied to 47- to 58-month-old animals that had never previously encountered one. We found that there was no difference in the change of food intake between the bucket condition and the puzzle feeder condition. In contrast, the time spent for consumption of food was three times longer in the puzzle feeder condition than in the bucket condition. Two monkeys initially exhibited stereotypic behavior. One showed a decreasing, and the other an increasing pattern of abnormal behavior after introduction of the puzzle feeder. In conclusion, this result suggests that over a short period, the puzzle feeder can only affect the time for food consumption since it failed to affect the food intake and did not consistently influence stereotypic behaviors in newly acquired rhesus monkeys.

  19. Effects of environmental and pharmacological manipulations on a novel delayed nonmatching-to-sample 'working memory' procedure in unrestrained rhesus monkeys.

    PubMed

    Hutsell, Blake A; Banks, Matthew L

    2015-08-15

    Working memory is a domain of 'executive function.' Delayed nonmatching-to-sample (DNMTS) procedures are commonly used to examine working memory in both human laboratory and preclinical studies. The aim was to develop an automated DNMTS procedure maintained by food pellets in rhesus monkeys using a touch-sensitive screen attached to the housing chamber. Specifically, the DNMTS procedure was a 2-stimulus, 2-choice recognition memory task employing unidimensional discriminative stimuli and randomized delay interval presentations. DNMTS maintained a delay-dependent decrease in discriminability that was independent of the retention interval distribution. Eliminating reinforcer availability during a single delay session or providing food pellets before the session did not systematically alter accuracy, but did reduce total choices. Increasing the intertrial interval enhanced accuracy at short delays. Acute Δ(9)-THC pretreatment produced delay interval-dependent changes in the forgetting function at doses that did not alter total choices. Acute methylphenidate pretreatment only decreased total choices. All monkeys were trained to perform NMTS at the 1s training delay within 60 days of initiating operant touch training. Furthermore, forgetting functions were reliably delay interval-dependent and stable over the experimental period (∼6 months). Consistent with previous studies, increasing the intertrial interval improved DNMTS performance, whereas Δ(9)-THC disrupted DNMTS performance independent of changes in total choices. Overall, the touchscreen-based DNMTS procedure described provides an efficient method for training and testing experimental manipulations on working memory in unrestrained rhesus monkeys. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Discriminative stimulus properties of intragastrically administered d-amphetamine and pentobarbital in rhesus monkeys.

    PubMed

    de la Garza, R; Johanson, C E

    1987-12-01

    Rhesus monkeys were trained to discriminate intragastrically administered d-amphetamine (AMPH) or pentobarbital (PENTO) from saline using a signaled shock-avoidance trail procedure. All monkeys maintained criterion levels (greater than 90% drug-appropriate responding) throughout the duration of the study during training sessions. In the AMPH experiment, the anorectics diethylpropion, mazindol, phendimetrazine, phenmetrazine and phentermine completely substituted for the training dose of AMPH. The atypical antidepressant bupropion and the psychomotor stimulant methylphenidate also completely substituted for AMPH. Other anorectics including benzphetamine, clortermine, fenetylline, mefenorex and the psychomotor stimulant pemoline that share some pharmacological properties with AMPH substituted for AMPH in some, but not all, of the monkeys tested. The anorectics fenfluramine and chlorphentermine failed to substitute for AMPH. Drugs from other pharmacological classes such as morphine, diazepam, nortripyline and PENTO also failed to substitute for AMPH, indicating pharmacological specificity. In the PENTO experiment, the benzodiazepines alprazolam, bromazepam, diazepam, flurazepam, halazepam, lorazepam, midazolam, oxazepam, temazepam and triazolam and the sedatives methaqualone and phenobarbital completely substituted for the training dose of PENTO. The nonbenzodiazepine anxiolytic CL 218,872 only partially substituted for PENTO. In addition, morphine and AMPH failed to substitute for PENTO, indicating pharmacological specificity. In summary, drugs delivered intragastrically functioned as discriminative stimuli in a drug-class specific manner. The ability to use drugs delivered by this route as discriminative stimuli provides a way to compare anorectic drugs to AMPH or sedative drugs to PENTO under conditions that resemble the mode of human consumption to determine whether these drugs are likely to be associated with AMPH-like or PENTO-like drug dependence.

  1. Inducible Nitric Oxide Synthase in Heart Tissue and Nitric Oxide in Serum of Trypanosoma cruzi-Infected Rhesus Monkeys: Association with Heart Injury

    PubMed Central

    Carvalho, Cristiano Marcelo Espinola; Silverio, Jaline Coutinho; da Silva, Andrea Alice; Pereira, Isabela Resende; Coelho, Janice Mery Chicarino; Britto, Constança Carvalho; Moreira, Otacílio Cruz; Marchevsky, Renato Sergio; Xavier, Sergio Salles; Gazzinelli, Ricardo Tostes; da Glória Bonecini-Almeida, Maria; Lannes-Vieira, Joseli

    2012-01-01

    Background The factors contributing to chronic Chagas' heart disease remain unknown. High nitric oxide (NO) levels have been shown to be associated with cardiomyopathy severity in patients. Further, NO produced via inducible nitric oxide synthase (iNOS/NOS2) is proposed to play a role in Trypanosoma cruzi control. However, the participation of iNOS/NOS2 and NO in T. cruzi control and heart injury has been questioned. Here, using chronically infected rhesus monkeys and iNOS/NOS2-deficient (Nos2 −/−) mice we explored the participation of iNOS/NOS2-derived NO in heart injury in T. cruzi infection. Methodology Rhesus monkeys and C57BL/6 and Nos2 −/− mice were infected with the Colombian T. cruzi strain. Parasite DNA was detected by polymerase chain reaction, T. cruzi antigens and iNOS/NOS2+ cells were immunohistochemically detected in heart sections and NO levels in serum were determined by Griess reagent. Heart injury was assessed by electrocardiogram (ECG), echocardiogram (ECHO), creatine kinase heart isoenzyme (CK-MB) activity levels in serum and connexin 43 (Cx43) expression in the cardiac tissue. Results Chronically infected monkeys presented conduction abnormalities, cardiac inflammation and fibrosis, which resembled the spectrum of human chronic chagasic cardiomyopathy (CCC). Importantly, chronic myocarditis was associated with parasite persistence. Moreover, Cx43 loss and increased CK-MB activity levels were primarily correlated with iNOS/NOS2+ cells infiltrating the cardiac tissue and NO levels in serum. Studies in Nos2 −/− mice reinforced that the iNOS/NOS2-NO pathway plays a pivotal role in T. cruzi-elicited cardiomyocyte injury and in conduction abnormalities that were associated with Cx43 loss in the cardiac tissue. Conclusion T. cruzi-infected rhesus monkeys reproduce features of CCC. Moreover, our data support that in T. cruzi infection persistent parasite-triggered iNOS/NOS2 in the cardiac tissue and NO overproduction might contribute to CCC

  2. Ranking Cognitive Flexibility in a Group Setting of Rhesus Monkeys with a Set-Shifting Procedure

    PubMed Central

    Shnitko, Tatiana A.; Allen, Daicia C.; Gonzales, Steven W.; Walter, Nicole A. R.; Grant, Kathleen A.

    2017-01-01

    Attentional set-shifting ability is an executive function underling cognitive flexibility in humans and animals. In humans, this function is typically observed during a single experimental session where dimensions of playing cards are used to measure flexibility in the face of changing rules for reinforcement (i.e., the Wisconsin Card Sorting Test (WCST)). In laboratory animals, particularly non-human primates, variants of the WCST involve extensive training and testing on a series of dimensional discriminations, usually in social isolation. In the present study, a novel experimental approach was used to assess attentional set-shifting simultaneously in 12 rhesus monkeys. Specifically, monkeys living in individual cages but in the same room were trained at the same time each day in a set-shifting task in the same housing environment. As opposed to the previous studies, each daily session began with a simple single-dimension discrimination regardless of the animal’s performance on the previous session. A total of eight increasingly difficult, discriminations (sets) were possible in each daily 45 min session. Correct responses were reinforced under a second-order schedule of flavored food pellet delivery, and criteria for completing a set was 12 correct trials out of a running total of 15 trials. Monkeys progressed through the sets at their own pace and abilities. The results demonstrate that all 12 monkeys acquired the simple discrimination (the first set), but individual differences in the ability to progress through all eight sets were apparent. A performance index (PI) that encompassed progression through the sets, errors and session duration was calculated and used to rank each monkey’s performance in relation to each other. Overall, this version of a set-shifting task results in an efficient assessment of reliable differences in cognitive flexibility in a group of monkeys. PMID:28386222

  3. Immunophenotypic characterization of the cutaneous exanthem of SIV-infected rhesus monkeys. Apposition of degenerative Langerhans cells and cytotoxic lymphocytes during the development of acquired immunodeficiency syndrome.

    PubMed Central

    Ringler, D. J.; Hancock, W. W.; King, N. W.; Letvin, N. L.; Daniel, M. D.; Desrosiers, R. C.; Murphy, G. F.

    1987-01-01

    A T-cell tropic retrovirus, simian immunodeficiency virus (SIV), has recently been isolated from immunodeficient rhesus monkeys. This virus has remarkable similarities to human immunodeficiency virus (HIV), the etiologic agent of acquired immunodeficiency syndrome. Subsequent studies of simian infection with SIV have shown it to be a relevant animal model for studying the pathogenesis of AIDS in man. In both HIV-infected humans and SIV-infected monkeys, a cutaneous maculopapular eruption has been described. To date, the pathogenesis and possible relationship of these exanthema to the evolution of systemic immunosuppression have remained obscure. In this study, the mononuclear cell infiltrates that characterize skin rashes of SIV-infected rhesus monkeys were found to be composed predominantly of cells with phenotypic characteristics of cytotoxic/suppressor (T8+) lymphocytes and natural killer cells. Many of these cells expressed membrane-bound interleukin-2 receptor molecules. Double labeling and immunoelectron microscopy revealed these cells in direct contact with degenerative Langerhans cells within the epidermis and dermis. These observations suggest that the cutaneous rash associated with SIV infection may be the consequence of target cell injury of Langerhans cells by effector cells with cytotoxic potential. Images Figure 1 Figure 2 Figure 3 PMID:3030113

  4. Toxicity in Rhesus Monkeys Following Administration of the 8-Aminoquinoline 8-[(4-amino-l-methylbutyl)amino]-5(l-hexyloxy)-6-methoxy-4-methylquinoline (WR242511)

    DTIC Science & Technology

    2008-09-01

    been synthesized) [17,18]. The rhesus monkey has also shown consistent MHb elevation follow- ing exposure to benzocaine as well as the 8...anesthetic-induced methemoglobinemia and sulfhemo- globinemia in macaques: a comparison of benzocaine and lido- caine. J Appl Toxicol 1995;15:153–158. 20

  5. FGF21 decreases body weight without reducing food intake or bone mineral density in high-fat fed obese rhesus macaque monkeys.

    PubMed

    Andersen, Birgitte; Straarup, Ellen M; Heppner, Kristy M; Takahashi, Diana L; Raffaele, Virginia; Dissen, Gregory A; Lewandowski, Katherine; Bödvarsdottir, Thóra B; Raun, Kirsten; Grove, Kevin L; Kievit, Paul

    2018-06-11

    Administration of FGF21 and FGF21 analogues reduce body weight; improve insulin sensitivity and dyslipidemia in animal models of obesity and in short term clinical trials. However potential adverse effects identified in mice have raised concerns for the development of FGF21 therapeutics. Therefore, this study was designed to address the actions of FGF21 on body weight, glucose and lipid metabolism and importantly its effects on bone mineral density (BMD), bone markers, and plasma cortisol in high-fat fed obese rhesus macaque monkeys. Obese non-diabetic rhesus macaque monkeys (five males and five ovariectomized (OVX) females) were maintained on a high-fat diet and treated for 12 weeks with escalating doses of FGF21. Food intake was assessed daily and body weight weekly. Bone mineral content (BMC) and BMD were measured by DEXA scanning prior to the study and on several occasions throughout the treatment period as well as during washout. Plasma glucose, glucose tolerance, insulin, lipids, cortisol, and bone markers were likewise measured throughout the study. On average, FGF21 decreased body weight by 17.6 ± 1.6% after 12 weeks of treatment. No significant effect on food intake was observed. No change in BMC or BMD was observed, while a 2-fold increase in CTX-1, a marker of bone resorption, was seen. Overall glucose tolerance was improved with a small but significant decrease in HbA 1C . Furthermore, FGF21 reduced concentrations of plasma triglycerides and very low density lipoprotein cholesterol. No adverse changes in clinical chemistry markers were demonstrated, and no alterations in plasma cortisol were observed during the study. In conclusion, FGF21 reduced body weight in obese rhesus macaque monkeys without reducing food intake. Furthermore, FGF21 had beneficial effects on body composition, insulin sensitivity, and plasma triglycerides. No adverse effects on bone density or plasma cortisol were observed after 12 weeks of treatment.

  6. Radioimmunoassay of arginine vasopressin in Rhesus Monkey plasma. [/sup 125/I tracer technique

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hayward, J.N.; Pavasuthipaisit, K.; Perez-Lopez, F.R.

    1976-04-01

    Using a new antiserum and an enzymatic radioiodination of arginine vasopressin (AVP), we have developed a sensitive and specific radioimmunoassay for plasma AVP in the monkey. The sensitivity of the assay is 0.5 ..mu..U/ml, the cross reaction with oxytocin (OT), minimal. We used this assay to study the effects that variations in blood osmolality have in regulating AVP secretion in unanesthetized, chair-restrained, chamber-isolated, adult female rhesus monkeys. Under water ad lib conditions, plasma AVP and osmolality were relatively constant, averaging 1.7 +- 0.6 (SD) ..mu..U/ml and 298 +- 3 mosmol/kg, respectively. Water loading decreased plasma AVP and osmolality to 0.6more » +- 0.2 ..mu..U/ml and 282 +- 6 mosmol/kg, respectively. When fluid restriction increased osmolality, plasma AVP rose progressively to twice the baseline after 1 day, and to 6 times the baseline after 3 days. The rise in plasma AVP was linearly correlated with the rise in osmolality (r = 0.93; P less than 0.001). Intravenous infusions of hypertonic saline produced significant rises in plasma osmolality and plasma AVP. There was a dose-related rise in plasma AVP that declined later at the expected rate with the infusion of physiological amounts of synthetic AVP.« less

  7. Kisspeptin and Neurokinin B Signaling Network Underlies the Pubertal Increase in GnRH Release in Female Rhesus Monkeys.

    PubMed

    Garcia, James P; Guerriero, Kathryn A; Keen, Kim L; Kenealy, Brian P; Seminara, Stephanie B; Terasawa, Ei

    2017-10-01

    Loss-of-function or inactivating mutations in the genes coding for kisspeptin and its receptor (KISS1R) or neurokinin B (NKB) and the NKB receptor (NK3R) in humans result in a delay in or the absence of puberty. However, precise mechanisms of kisspeptin and NKB signaling in the regulation of the pubertal increase in gonadotropin-releasing hormone (GnRH) release in primates are unknown. In this study, we conducted a series of experiments infusing agonists and antagonists of kisspeptin and NKB into the stalk-median eminence, where GnRH, kisspeptin, and NKB neuroterminal fibers are concentrated, and measuring GnRH release in prepubertal and pubertal female rhesus monkeys. Results indicate that (1) similar to those previously reported for GnRH stimulation by the KISS1R agonist (i.e., human kisspeptin-10), the NK3R agonist senktide stimulated GnRH release in a dose-responsive manner in both prepubertal and pubertal monkeys; (2) the senktide-induced GnRH release was blocked in the presence of the KISS1R antagonist peptide 234 in pubertal but not prepubertal monkeys; and (3) the kisspeptin-induced GnRH release was blocked in the presence of the NK3R antagonist SB222200 in the pubertal but not prepubertal monkeys. These results are interpreted to mean that although, in prepubertal female monkeys, kisspeptin and NKB signaling to GnRH release is independent, in pubertal female monkeys, a reciprocal signaling mechanism between kisspeptin and NKB neurons is established. We speculate that this cooperative mechanism by the kisspeptin and NKB network underlies the pubertal increase in GnRH release in female monkeys. Copyright © 2017 Endocrine Society.

  8. Topographic and age-related changes of the retinal epithelium and Bruch's membrane of rhesus monkeys.

    PubMed

    Gouras, Peter; Ivert, Lena; Neuringer, Martha; Mattison, Julie A

    2010-07-01

    To examine structural differences in the retinal pigmented epithelium (RPE) and Bruch's membrane of rhesus monkeys (Macaca mulatta) as a function of topography and age. The retinas of two old (24 and 26 years old) and two young (1 and 6 years old) female monkeys were examined by light fluorescence and electron microscopy at the macula, equator, and ora serrata. All monkeys lacked fluorescence and lipofuscin granules in the RPE at the ora serrata where photoreceptors are absent. The equator and macula showed intense fluorescence and many lipofuscin granules in the RPE of the old but not the young monkeys. At the ora, the RPE contained many dense round melanin granules throughout the cell. At the equator and macula, melanin granules were more apical, less frequent, and often elongated. Mitochondria were clustered at the basal side of the RPE cell near infolds of the plasma membrane. Both mitochondria and infolds tended to increase toward the macula. In all regions, the basal lamina of the RPE did not penetrate the extracellular space adjacent to infolds. The elastin layer of Bruch's membrane was wide at the ora and equator and thinner at the macula. In the old monkeys, drusen were found at all retinal regions between the basal lamina and the internal collagen layer of Bruch's membrane. The drusen were often membrane-bound with a basal lamina and contained material resembling structures in the RPE. Lack of fluorescence and lipofuscin in the RPE at the ora serrata, where photoreceptors are absent, confirms that RPE fluorescence occurs only where outer segments are phagocytized. Mitochondrial clustering indicates that the basal side of the RPE cell uses the most energy and this becomes maximal at the macula. The presence of age-related degenerative changes and drusen at all retinal locations in the older monkeys, even at the ora where RPE lipofuscin was absent, indicates that these processes are not dependent on local lipofuscin accumulation. Therefore lipofuscin

  9. Optimal iron fortification of maternal diet during pregnancy and nursing for investigating and preventing iron deficiency in young rhesus monkeys.

    PubMed

    Coe, Christopher L; Lubach, Gabriele R; Busbridge, Mark; Chapman, Richard S

    2013-06-01

    The realization that pregnant and infant monkeys were challenged by high nutritional needs for iron led vendors to markedly increase iron concentrations in commercial diets. Yet, no systematic research was conducted to investigate the consequences of this important dietary change. Hematology and iron panels were determined for 142 infant rhesus monkeys gestated and reared on 3 different diets varying in iron concentration (180, 225 or 380 mg Fe/kg). Anemia was significantly more prevalent in offspring from females fed the 180 and 225 mg Fe/kg diets (32-41% versus 0 for the 380 mg Fe/kg diet, P<0.001). Higher hepcidin levels were protective against iron overload in infants from the 380 mg Fe/kg condition. These findings indicate a highly fortified diet during pregnancy continues to have postnatal benefits for the growing infant. However, for those interested in iron deficiency, lower iron diets provide a reliable way to generate anemic infant monkeys for research. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) in rats and rhesus monkeys: Effect of anatomical site

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moody, R.P.; Ritter, L.

    1989-01-01

    Dermal absorption of the insecticide lindane (1 delta, 2 delta, 3 beta, 4 delta, 5 delta, 6 beta-hexachlorocyclohexane) was determined in rats and rhesus monkeys. Lindane is in widespread use as a 1% cream or lotion scabicide formulation and as a 1% miticide shampoo for body lice control in humans. Results obtained following our in vivo dermal absorption procedure demonstrated that 18 +/- 4.1%, 34 +/- 5.2%, and 54 +/- 26.3% of the applied dose was absorbed following topical applications at a rate of 1.5 micrograms/cm2 (6.2 micrograms/100 microliters of acetone) of the 14C-labeled pesticide to 4.2-cm2 regions of themore » forearm (n = 8), forehead (n = 7), and palm (n = 4) of rhesus monkeys, respectively. Dose sites were washed with soapy water 24 h posttreatment. Comparative studies in rats (n = 5) dosed middorsally demonstrated 31 +/- 9.5% absorption. Statistical analysis of the 14C excretion kinetics demonstrated slower clearance of lindane from rats than monkey forearm, forehead, or palm. Intramuscular (im) injections of 14C-lindane gave 52 +/- 7.1% recovery in monkey (n = 8) and 64 +/- 5.9% in rats (n = 5), suggesting body storage of this lipophilic chemical.« less

  11. Development of a flow feedback pulse duplicator system with rhesus monkey arterial input impedance characteristics

    NASA Technical Reports Server (NTRS)

    Schaub, J. D.; Koenig, S. C.; Schroeder, M. J.; Ewert, D. L.; Drew, G. A.; Swope, R. D.; Convertino, V. A. (Principal Investigator)

    1999-01-01

    An in vitro pulsatile pump flow system that is capable of producing physiologic pressures and flows in a mock circulatory system tuned to reproduce the first nine harmonics of the input impedance of a rhesus monkey was developed and tested. The system was created as a research tool for evaluating cardiovascular function and for the design, testing, and evaluation of electrical-mechanical cardiovascular models and chronically implanted sensors. The system possesses a computerized user interface for controlling a linear displacement pulsatile pump in a controlled flow loop format to emulate in vivo cardiovascular characteristics. Evaluation of the pump system consisted of comparing its aortic pressure and flow profiles with in vivo rhesus hemodynamic waveforms in the time and frequency domains. Comparison of aortic pressure and flow data between the pump system and in vivo data showed good agreement in the time and frequency domains, however, the pump system produced a larger pulse pressure. The pump system can be used for comparing cardiovascular parameters with predicted cardiovascular model values and for evaluating such items as vascular grafts, heart valves, biomaterials, and sensors. This article describes the development and evaluation of this feedback controlled cardiovascular dynamics simulation modeling system.

  12. Cardiovascular results from a rhesus monkey flown aboard the Cosmos 1514 spaceflight

    NASA Technical Reports Server (NTRS)

    Sandler, H.; Hines, J.; Benjamin, B. A.; Halpryn, B. M.; Krotov, V. P.

    1987-01-01

    The results of the Cosmos 1514 cardiovascular experiment, in which the blood flow to the head and the carotid pressure of a rhesus monkey were measured during the 5-d spaceflight, are reported. A single cylindrical probe containing both pressure and flow transducers was chronically implanted as a cuff around the left common carotid artery; measurements were obtained for 4 min every 2 h and compared to identical recordings obtained during a preflight control period and during 12 h on a launch pad. Immediately on its insertion into orbit, mean arterial pressure increased by 10 percent and has maintained a 16-27 percent increase over the first few hours of flight before returning to baseline level. Blood flow showed reciprocal changes to pressure on orbital insertion. Cardiovascular system changes persisted into the second day of flight, with the signs of adaptation appearing on days 3-5.

  13. Prototype Abstraction by Monkeys ("Macaca Mulatta")

    ERIC Educational Resources Information Center

    Smith, J. David; Redford, Joshua S.; Haas, Sarah M.

    2008-01-01

    The authors analyze the shape categorization of rhesus monkeys ("Macaca mulatta") and the role of prototype- and exemplar-based comparison processes in monkeys' category learning. Prototype and exemplar theories make contrasting predictions regarding performance on the Posner-Homa dot-distortion categorization task. Prototype theory--which…

  14. Orientation perception in rhesus monkeys (Macaca mulatta).

    PubMed

    Wakita, Masumi

    2008-07-01

    It was previously demonstrated that monkeys divide the orientation continuum into cardinal and oblique categories. However, it is still unclear how monkeys perceive within-category orientations. To better understand monkeys' perception of orientation, two experiments were conducted using five monkeys. In experiment 1, they were trained to identify either one cardinal or one oblique target orientation out of six orientations. The results showed that they readily identified the cardinal target whether it was oriented horizontally or vertically. However, a longer training period was needed to identify the oblique target orientation regardless of its degree and direction of tilt. In experiment 2, the same monkeys were trained to identify two-oblique target orientations out of six orientations. These orientations were paired, either sharing the degree of tilt, direction of tilt, or neither property. The results showed that the monkeys readily identified oblique orientations when they had either the same degree or direction of tilt. However, when the target orientations had neither the same degree nor direction of tilt, the animals had difficulty in identifying them. In summary, horizontal and vertical orientations are individually processed, indicating that monkeys do not have a category for cardinal orientation, but they may recognize cardinal orientations as non-obliques. In addition, monkeys efficiently abstract either the degree or the direction of tilt from oblique orientations, but they have difficulty combining these features to identify an oblique orientation. Thus, not all orientations within the oblique category are equally perceived.

  15. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring.

    PubMed

    Abbott, David H; Bruns, Cristin R; Barnett, Deborah K; Dunaif, Andrea; Goodfriend, Theodore L; Dumesic, Daniel A; Tarantal, Alice F

    2010-11-01

    Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of testosterone propionate (TP) subcutaneously daily from 40 to 80 days (first to second trimesters) of gestation [term, mean (range): 165 (155-175) days], whereas an additional six such females received oil vehicle injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by cesarean section for postnatal studies. Blood samples were collected from dams and infants for glucose, insulin, and total free fatty acid (FFA) determinations. TP injections transiently accelerated maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses, and modestly increased weight gain in infancy compared with concurrent controls. Mild to moderate glucose intolerance, with increased area-under-the-curve circulating insulin values, occurred in TP-injected dams during an intravenous glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester intravenous glucagon-tolbutamide challenge (140 days gestation), whereas excessive insulin sensitivity and increased insulin secretion relative to insulin sensitivity occurred in PA infants during an intravenous glucose-tolbutamide test at ∼1.5 mo postnatal age. Data from these studies suggest that experimentally induced fetal androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in

  16. Experimentally induced gestational androgen excess disrupts glucoregulation in rhesus monkey dams and their female offspring

    PubMed Central

    Bruns, Cristin R.; Barnett, Deborah K.; Dunaif, Andrea; Goodfriend, Theodore L.; Dumesic, Daniel A.; Tarantal, Alice F.

    2010-01-01

    Discrete fetal androgen excess during early gestation in rhesus monkeys (Macaca mulatta) promotes endocrine antecedents of adult polycystic ovary syndrome (PCOS)-like traits in female offspring. Because developmental changes promoting such PCOS-like metabolic dysfunction remain unclear, the present study examined time-mated, gravid rhesus monkeys with female fetuses, of which nine gravid females received 15 mg of testosterone propionate (TP) subcutaneously daily from 40 to 80 days (first to second trimesters) of gestation [term, mean (range): 165 (155–175) days], whereas an additional six such females received oil vehicle injections over the same time interval. During gestation, ultrasonography quantified fetal growth measures and was used as an adjunct for fetal blood collections. At term, all fetuses were delivered by cesarean section for postnatal studies. Blood samples were collected from dams and infants for glucose, insulin, and total free fatty acid (FFA) determinations. TP injections transiently accelerated maternal weight gain in dams, very modestly increased head diameter of prenatally androgenized (PA) fetuses, and modestly increased weight gain in infancy compared with concurrent controls. Mild to moderate glucose intolerance, with increased area-under-the-curve circulating insulin values, occurred in TP-injected dams during an intravenous glucose tolerance test in the early second trimester. Moreover, reduced circulating FFA levels occurred in PA fetuses during a third trimester intravenous glucagon-tolbutamide challenge (140 days gestation), whereas excessive insulin sensitivity and increased insulin secretion relative to insulin sensitivity occurred in PA infants during an intravenous glucose-tolbutamide test at ∼1.5 mo postnatal age. Data from these studies suggest that experimentally induced fetal androgen excess may result in transient hyperglycemic episodes in the intrauterine environment that are sufficient to induce relative increases in

  17. Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

    1998-01-01

    Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 degrees head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 degrees upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alternating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

  18. Effects of 12 days exposure to simulated microgravity on central circulatory hemodynamics in the rhesus monkey

    NASA Astrophysics Data System (ADS)

    Convertino, V. A.; Koenig, S. C.; Krotov, V. P.; Fanton, J. W.; Korolkov, V. I.; Trambovetsky, E. V.; Ewert, D. L.; Truzhennikov, A.; Latham, R. D.

    Central circulatory hemodynamic responses were measured before and during the initial 9 days of a 12-day 10 ° head-down tilt (HDT) in 4 flight-sized juvenile rhesus monkeys who were surgically instrumented with a variety of intrathoracic catheters and blood flow sensors to assess the effects of simulated microgravity on central circulatory hemodynamics. Each subject underwent measurements of aortic and left ventricular pressures, and aortic flow before and during HDT as well as during a passive head-up postural test before and after HDT. Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure were measured, and dP/dt and left ventricular elastance was calculated from hemodynamic measurements. The postural test consisted of 5 min of supine baseline control followed by 5 minutes of 90 ° upright tilt (HUT). Heart rate, stroke volume, cardiac output, and left ventricular end-diastolic pressure showed no consistent alterations during HDT. Left ventricular elastance was reduced in all animals throughout HDT, indicating that cardiac compliance was increased. HDT did not consistently alter left ventricular +dP/dt, indicating no change in cardiac contractility. Heart rate during the post-HDT HUT postural test was elevated compared to pre-HDT while post-HDT cardiac output was decreased by 52% as a result of a 54% reduction in stroke volume throughout HUT. Results from this study using an instrumented rhesus monkey suggest that exposure to microgravity may increase ventricular compliance without alterating cardiac contractility. Our project supported the notion that an invasively-instrumented animal model should be viable for use in spaceflight cardiovascular experiments to assess potential changes in myocardial function and cardiac compliance.

  19. Effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in male rhesus monkeys.

    PubMed

    Schwienteck, Kathryn L; Negus, S Stevens; Poklis, Justin L; Banks, Matthew L

    2015-10-01

    One complicating factor in cocaine addiction may be concurrent exposure and potential dependence on nicotine. The aim of the present study was to determine the effects of continuous nicotine treatment and subsequent termination on cocaine versus food choice in rhesus monkeys (Macaca mulatta). For comparison, we also determined effects of the nicotinic receptor antagonist mecamylamine on cocaine versus food choice during continuous saline and nicotine treatment. Rhesus monkeys (N = 3) responded under a concurrent schedule of food pellet (1 g) and intravenous cocaine (0-0.1 mg/kg/injection) availability. Saline and ascending nicotine doses (0.1-1.0 mg/kg/hr, intravenous) were continuously infused for 7-day treatment periods and separated by 24-hr saline treatment periods. Acute effects of mecamylamine (0.32-1.8 mg/kg, intramuscular, 15 min pretreatment) were determined during continuous saline and 0.32-mg/kg/hr nicotine treatments. During saline treatment, cocaine maintained a dose-dependent increase in cocaine choice. Nicotine treatment did not alter cocaine versus food choice. In contrast, preference of 0.032 mg/kg/injection cocaine was attenuated 24 hr following termination of 0.32-mg/kg/hr nicotine treatment, despite no somatic abstinence signs being observed. Acute mecamylamine enhanced cocaine choice during saline treatment and mainly suppressed rates of behavior during nicotine treatment. Overall, continuous nicotine exposure, up to 1 mg/kg/hr, does not enhance cocaine choice and does not produce nicotine dependence, as demonstrated by the lack of abstinence signs. (c) 2015 APA, all rights reserved).

  20. Gonadotropin-binding sites in the rhesus monkey ovary: role of the vasculature in the selective distribution of human chorionic gonadotropin to the preovulatory follicle

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zeleznik, A.J.; Schuler, H.M.; Reichert, L.E. Jr.

    These experiments were initiated to determine if differences exist in the vasculature of individual follicles in the rhesus monkey ovary during the late follicular phase of the menstrual cycle and to determine whether differences in vascularity result in differential exposure of certain follicles to gonadotropic hormones. The density of blood vessels within the thecal layer of the dominant follicle and other antral follicles was determined in ovaries from four animals removed on day 9 or 10 of the menstrual cycle. Blood vessels were identified using a histochemical stain for hemoglobin. Morphometric analysis indicated that the percentage of the thecal layermore » occupied by blood vessels in the dominant follicles (48%) was significantly greater (P less than 0.005) than that of other smaller antral follicles either within the same ovary as the dominant follicle (24%) or in the contralateral ovary (26%). To determine if differences in vascularity result in a differential supply of gonadotropins to the dominant follicle, we studied, by autoradiography, the in vivo and in vitro binding of (125I)hCG in four rhesus monkeys on day 9 of the menstrual cycle. Results of in vitro binding studies indicated that the thecal layer of virtually every antral follicle possessed hCG-binding sites. However, when (125I)hcg was injected iv into animals and allowed to distribute via the vasculature, the dominant follicle was heavily labeled while other smaller antral follicles accumulated little, if any, radioiodinated hCG. These observations indicate that increased vascularization of individual follicles results in preferential delivery of gonadotropins, and suggest that blood flow to individual follicles may play an instrumental role in the selective maturation of the preovulatory follicle in the rhesus monkey.« less

  1. Tolerance of Vascularized Islet-Kidney Transplants in Rhesus Monkeys

    PubMed Central

    Pathiraja, Vimukthi; Villani, Vincenzo; Tasaki, Masayuki; Matar, Abraham J.; Duran-Struuck, Raimon; Yamada, Rei; Moran, Shannon G.; Clayman, Eric S.; Hanekamp, John; Shimizu, Akira; Sachs, David H.; Huang, Christene A.; Yamada, Kazuhiko

    2016-01-01

    We have previously reported that transplantation (Tx) of prevascularized donor islets as composite Islet-Kidneys (IK) reversed diabetic hyperglycemia in both miniature swine and baboons. In order to enhance this strategy's potential clinical applicability, we have now combined this approach with hematopoietic stem cells (HSC) Tx in an attempt to induce tolerance in non-human primates. IKs were prepared by isolating islets from 70% partial pancreatectomies and injecting them beneath the autologous renal capsule of five rhesus monkey donors at least 3 months before allogeneic IKTx. HSCTx was performed following mobilization and leukapheresis of the donors, and conditioning of the recipients with total body irradiation, T-cell depletion and cyclosporine. One IK was harvested for histologic analysis and four were transplanted into diabetic recipients. IKTx was performed either 20–22 (n=3) or 208 (n=1) days after HSCTx. All animals accepted IKs without rejection. All recipients required >20 U/day of insulin before IKTx to maintain less than 200mg/dl, whereas after IKTx 3 animals required minimal doses of insulin (1–3 U/day) and one animal was insulin-free. These results constitute a proof-of-principle that this IK tolerance strategy may provide a cure for both end-stage renal disease and diabetes without the need for immunosuppression. PMID:27376692

  2. An alert of Mycobacterium tuberculosis infection of rhesus macaques in a wild zoo in China.

    PubMed

    Gong, Wenping; Yang, Yourong; Luo, Yi; Li, Ning; Bai, Xuejuan; Liu, Yinping; Zhang, Junxian; Chen, Ming; Zhang, Chenglin; Wu, Xueqiong

    2017-10-30

    Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB), is becoming increasingly recognized as an important cause of fatal chronic illnesses in China. In this study, we report an infectious disease among 84 rhesus macaques at a Chinese zoo. Their clinical signs and symptoms were very similar with the manifestations of TB in humans. To determine the potential pathogens of this outbreak, many methods were used. First, tuberculin skin tests showed that none of the monkeys displayed significant skin reactions. Subsequently, the sera were tested for specific antibody IgG; 29 (34.5%) and 39 (46.4%) blood samples tested positive by TB-IgG and TB-DOT, respectively. Radiographic examination showed characteristic imageology changes in 14 (16.7%) monkeys. One individual determined as positive by the above three methods was euthanized, and histopathological analysis demonstrated typical granulomas and caseous necrosis in the lung, liver, spleen, and intestine. Furthermore, the pathogenic mycobacteria were isolated from lung lobe, cultured on acidic Lowenstein-Jensen culture medium, and identified as M. tuberculosis by real-time PCR and DNA sequencing. Nevertheless, the origin of the infection remained unknown. These findings emphasize the need to strengthen the management and training of staff, especially those working at animal shelters.

  3. An alert of Mycobacterium tuberculosis infection of rhesus macaques in a wild zoo in China

    PubMed Central

    Gong, Wenping; Yang, Yourong; Luo, Yi; Li, Ning; Bai, Xuejuan; Liu, Yinping; Zhang, Junxian; Chen, Ming; Zhang, Chenglin; Wu, Xueqiong

    2017-01-01

    Mycobacterium tuberculosis, the pathogen that causes tuberculosis (TB), is becoming increasingly recognized as an important cause of fatal chronic illnesses in China. In this study, we report an infectious disease among 84 rhesus macaques at a Chinese zoo. Their clinical signs and symptoms were very similar with the manifestations of TB in humans. To determine the potential pathogens of this outbreak, many methods were used. First, tuberculin skin tests showed that none of the monkeys displayed significant skin reactions. Subsequently, the sera were tested for specific antibody IgG; 29 (34.5%) and 39 (46.4%) blood samples tested positive by TB-IgG and TB-DOT, respectively. Radiographic examination showed characteristic imageology changes in 14 (16.7%) monkeys. One individual determined as positive by the above three methods was euthanized, and histopathological analysis demonstrated typical granulomas and caseous necrosis in the lung, liver, spleen, and intestine. Furthermore, the pathogenic mycobacteria were isolated from lung lobe, cultured on acidic Lowenstein-Jensen culture medium, and identified as M. tuberculosis by real-time PCR and DNA sequencing. Nevertheless, the origin of the infection remained unknown. These findings emphasize the need to strengthen the management and training of staff, especially those working at animal shelters. PMID:28659540

  4. Culture of prostate epithelial cells of the rhesus monkey on extracellular matrix substrate: influence of steroids and insulin-like growth factors.

    PubMed

    Udayakumar, T S; Jeyaraj, D A; Rajalakshmi, M; Sharma, R S

    1999-09-01

    Rhesus monkey prostate epithelial cells from the cranial lobe were isolated and cultured in flasks coated either with collagen IV or laminin. The effects of stromal cell medium, androgens and growth factors on cell number, thymidine incorporation and secretory activity were assessed. The results indicate that dihydrotestosterone (DHT) and androstenedione have stimulatory influences on cell proliferation and secretion in coated flasks. DHT was more effective in increasing cell number but the induction of secretory activity was similar with both steroids. The combination of IGF-I and -II resulted in inducing better cell proliferation and secretory activity than the individual IGFs but, of the two IGFs, IGF-I was more effective than IGF-II. DHT with IGFs was more potent in inducing proliferation, differentiation and secretion than androstenedione. Even in the absence of steroids or growth factors, colony formation and confluence occurred in coated flasks but cell differentiation and secretion only to a limited extent. In conclusion, we were able to establish an in vitro primary culture of prostate epithelial cells from rhesus monkey using extracellular matrix proteins, steroids and growth factors as additional supplements. This culture system may be useful to study prostate cell physiology and to identify drugs that can inhibit cell proliferation.

  5. Rhesus monkey sperm cryopreservation with TEST-yolk extender in the absence of permeable cryoprotectant.

    PubMed

    Dong, Qiaoxiang; Correa, Liane M; VandeVoort, Catherine A

    2009-02-01

    Recently, there has been increased interest in ultra-rapid freezing with mammalian spermatozoa, especially for vitrification in the absence of cryoprotectants. Sperm cryopreservation in non-human primates has been successful, but the use of frozen-thawed sperm in standard artificial insemination (AI) remains difficult, and removal of permeable cryoprotectant may offer opportunities for increased AI success. The present study intended to explore the possibility of freezing rhesus monkey sperm in the absence of permeable cryoprotectants. Specifically, we evaluated various factors such as presence or absence of egg yolk, the percentage of egg yolk in the extenders, and the effect of cooling and thawing rate on the success of freezing without permeable cryoprotectants. Findings revealed that freezing with TEST in the absence of egg yolk offers little protection (<15% post-thaw motility). Egg yolk of 40% or more in TEST resulted in decreased motility, while egg yolk in the range of 20-30% yielded the most motile sperm. Cooling at a slow rate (29 degrees C/min) reduced post-thaw motility significantly for samples frozen with TEST-yolk alone, but had no effect for controls in the presence of glycerol. Similarly, slow thawing in room temperature air is detrimental for freezing without permeable cryoprotectant (<2% motility). In addition to motility, the ability of sperm to capacitate based on an increase in intracellular calcium levels upon activation with cAMP and caffeine suggested no difference between fresh and frozen-thawed motile sperm, regardless of treatment. In summary, the present study demonstrates that ejaculated and epididymal sperm from rhesus monkeys can be cryopreserved with TEST-yolk (20%) in the absence of permeable cryoprotectant when samples were loaded in a standard 0.25-mL straw, cooled rapidly in liquid nitrogen vapor at 220 degrees C/min, and thawed rapidly in a 37 degrees C water bath. This study also represents the first success of freezing

  6. Use of primary cell cultures to measure the late effects in the skins of rhesus monkeys irradiated with protons

    NASA Astrophysics Data System (ADS)

    Cox, A. B.; Wood, D. H.; Lett, J. T.

    Previous pilot investigations of the uses of primary cell cultures to study late damage in stem cells of the skin of the New Zealand white (NZW) rabbit and the rhesus monkey /1-3/, have been extended to individual monkeys exposed to 55 MeV protons. Protons of this energy have a larger range in tissue of (~2.6 cm) than the 32 MeV protons (~0.9 cm) to which the animals in our earlier studies had been exposed. Although the primary emphases in the current studies were improvement and simplification in the techniques and logistics of transportation of biopsies to a central analytical facility, comparison of the quantitative measurements obtained thus far for survival of stem cells in the skins from animals irradiated 21 years ago reveals that the effects of both proton energies are similar.

  7. Promoter methylation and age-related downregulation of Klotho in rhesus monkey.

    PubMed

    King, Gwendalyn D; Rosene, Douglas L; Abraham, Carmela R

    2012-12-01

    While overall DNA methylation decreases with age, CpG-rich areas of the genome can become hypermethylated. Hypermethylation near transcription start sites typically decreases gene expression. Klotho (KL) is important in numerous age-associated pathways including insulin/IGF1 and Wnt signaling and naturally decreases with age in brain, heart, and liver across species. Brain tissues from young and old rhesus monkeys were used to determine whether epigenetic modification of the KL promoter underlies age-related decreases in mRNA and protein levels of KL. The KL promoter in genomic DNA from brain white matter did not show evidence of oxidation in vivo but did exhibit an increase in methylation with age. Further analysis identified individual CpG motifs across the region of interest with increased methylation in old animals. In vitro methyl modification of these individual cytosine residues confirmed that methylation of the promoter can decrease gene transcription. These results provide evidence that changes in KL gene expression with age may, at least in part, be the result of epigenetic changes to the 5' regulatory region.

  8. Discriminative and Reinforcing Stimulus Effects of Nicotine, Cocaine, and Cocaine + Nicotine Combinations in Rhesus Monkeys

    PubMed Central

    Mello, Nancy K.; Newman, Jennifer L.

    2011-01-01

    Concurrent cigarette smoking and cocaine use is well documented. However, the behavioral pharmacology of cocaine and nicotine combinations is poorly understood, and there is a need for animal models to examine this form of polydrug abuse. The purpose of this study was two-fold: first to assess the effects of nicotine on the discriminative stimulus effects of cocaine, and second, to study self-administration of nicotine/cocaine combinations in a novel polydrug abuse model. In drug discrimination experiments, nicotine increased the discriminative stimulus effects of low cocaine doses in two of three monkeys, but nicotine did not substitute for cocaine in any monkey. Self-administration of cocaine and nicotine alone, and cocaine + nicotine combinations was studied under a second-order fixed ratio 2, variable ratio 16 (FR2[VR16:S]) schedule of reinforcement. Cocaine and nicotine alone were self-administered in a dose-dependent manner. The combination of marginally reinforcing doses of cocaine and nicotine increased drug self-administration behavior above levels observed with the same dose of either cocaine or nicotine alone. These findings indicate that nicotine may increase cocaine’s discriminative stimulus and reinforcing effects in rhesus monkeys, and illustrate the feasibility of combining cocaine and nicotine in a preclinical model of polydrug abuse. Further studies of the behavioral effects of nicotine + cocaine combinations will contribute to our understanding the pharmacology of dual nicotine and cocaine dependence, and will be useful for evaluation of new treatment medications. PMID:21480727

  9. Long-Term Exposure to Oral Methylphenidate or dl-Amphetamine Mixture in Peri-Adolescent Rhesus Monkeys: Effects on Physiology, Behavior, and Dopamine System Development

    PubMed Central

    Soto, Paul L; Wilcox, Kristin M; Zhou, Yun; Ator, Nancy A; Riddle, Mark A; Wong, Dean F; Weed, Michael R

    2012-01-01

    The stimulants methylphenidate and amphetamine are used to treat children with attention deficit/hyperactivity disorder over important developmental periods, prompting concerns regarding possible long-term health impact. This study assessed the effects of such a regimen in male, peri-adolescent rhesus monkeys on a variety of cognitive/behavioral, physiological, and in vivo neurochemical imaging parameters. Twice daily (0900 and 1200 hours), for a total of 18 months, juvenile male monkeys (8 per group) consumed either an unadulterated orange-flavored solution, a methylphenidate solution, or a dl-amphetamine mixture. Doses were titrated to reach blood/plasma levels comparable to therapeutic levels in children. [11C]MPH and [11C]raclopride dynamic PET scans were performed to image dopamine transporter and D2-like receptors, respectively. Binding potential (BPND), an index of tracer-specific binding, and amphetamine-induced changes in BPND of [11C]raclopride were estimated by kinetic modeling. There were no consistent differences among groups on the vast majority of measures, including cognitive (psychomotor speed, timing, inhibitory control, cognitive flexibility), general activity, physiological (body weight, head circumference, crown-to-rump length), and neurochemical (ie, developmental changes in dopamine transporter, dopamine D2 receptor density, and amphetamine-stimulated dopamine release were as expected). Cytogenetic studies indicated that neither drug was a clastogen in rhesus monkeys. Thus, methylphenidate and amphetamine at therapeutic blood/plasma levels during peri-adolescence in non-human primates have little effect on physiological or behavioral/cognitive development. PMID:22805599

  10. Long-term exposure to oral methylphenidate or dl-amphetamine mixture in peri-adolescent rhesus monkeys: effects on physiology, behavior, and dopamine system development.

    PubMed

    Soto, Paul L; Wilcox, Kristin M; Zhou, Yun; Kumar, Anil; Ator, Nancy A; Riddle, Mark A; Wong, Dean F; Weed, Michael R

    2012-11-01

    The stimulants methylphenidate and amphetamine are used to treat children with attention deficit/hyperactivity disorder over important developmental periods, prompting concerns regarding possible long-term health impact. This study assessed the effects of such a regimen in male, peri-adolescent rhesus monkeys on a variety of cognitive/behavioral, physiological, and in vivo neurochemical imaging parameters. Twice daily (0900 and 1200 hours), for a total of 18 months, juvenile male monkeys (8 per group) consumed either an unadulterated orange-flavored solution, a methylphenidate solution, or a dl-amphetamine mixture. Doses were titrated to reach blood/plasma levels comparable to therapeutic levels in children. [¹¹C]MPH and [¹¹C]raclopride dynamic PET scans were performed to image dopamine transporter and D₂-like receptors, respectively. Binding potential (BP(ND)), an index of tracer-specific binding, and amphetamine-induced changes in BP(ND) of [¹¹C]raclopride were estimated by kinetic modeling. There were no consistent differences among groups on the vast majority of measures, including cognitive (psychomotor speed, timing, inhibitory control, cognitive flexibility), general activity, physiological (body weight, head circumference, crown-to-rump length), and neurochemical (ie, developmental changes in dopamine transporter, dopamine D₂ receptor density, and amphetamine-stimulated dopamine release were as expected). Cytogenetic studies indicated that neither drug was a clastogen in rhesus monkeys. Thus, methylphenidate and amphetamine at therapeutic blood/plasma levels during peri-adolescence in non-human primates have little effect on physiological or behavioral/cognitive development.

  11. La Crosse virus infectivity, pathogenesis, and immunogenicity in mice and monkeys

    PubMed Central

    Bennett, Richard S; Cress, Christina M; Ward, Jerrold M; Firestone, Cai-Yen; Murphy, Brian R; Whitehead, Stephen S

    2008-01-01

    Background La Crosse virus (LACV), family Bunyaviridae, was first identified as a human pathogen in 1960 after its isolation from a 4 year-old girl with fatal encephalitis in La Crosse, Wisconsin. LACV is a major cause of pediatric encephalitis in North America and infects up to 300,000 persons each year of which 70–130 result in severe disease of the central nervous system (CNS). As an initial step in the establishment of useful animal models to support vaccine development, we examined LACV infectivity, pathogenesis, and immunogenicity in both weanling mice and rhesus monkeys. Results Following intraperitoneal inoculation of mice, LACV replicated in various organs before reaching the CNS where it replicates to high titer causing death from neurological disease. The peripheral site where LACV replicates to highest titer is the nasal turbinates, and, presumably, LACV can enter the CNS via the olfactory neurons from nasal olfactory epithelium. The mouse infectious dose50 and lethal dose50 was similar for LACV administered either intranasally or intraperitoneally. LACV was highly infectious for rhesus monkeys and infected 100% of the animals at 10 PFU. However, the infection was asymptomatic, and the monkeys developed a strong neutralizing antibody response. Conclusion In mice, LACV likely gains access to the CNS via the blood stream or via olfactory neurons. The ability to efficiently infect mice intranasally raises the possibility that LACV might use this route to infect its natural hosts. Rhesus monkeys are susceptible to LACV infection and develop strong neutralizing antibody responses after inoculation with as little as 10 PFU. Mice and rhesus monkeys are useful animal models for LACV vaccine immunologic testing although the rhesus monkey model is not optimal. PMID:18267012

  12. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Lucas, J. N.; Hill, F. S.; Burk, C. E.; Cox, A. B.; Straume, T.

    1996-01-01

    Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

  13. Stability of the translocation frequency following whole-body irradiation measured in rhesus monkeys.

    PubMed

    Lucas, J N; Hill, F S; Burk, C E; Cox, A B; Straume, T

    1996-09-01

    Chromosome translocations are persistent indicators of prior exposure to ionizing radiation and the development of 'chromosome painting' to efficiently detect translocations has resulted in a powerful biological dosimetry tool for radiation dose reconstruction. However, the actual stability of the translocation frequency with time after exposure must be measured before it can be used reliably to obtain doses for individuals exposed years or decades previously. Human chromosome painting probes were used here to measure reciprocal translocation frequencies in cells from two tissues of 8 rhesus monkeys (Macaca mulatta) irradiated almost three decades previously. Six of the monkeys were exposed in 1965 to whole-body (fully penetrating) radiation and two were unexposed controls. The primates were irradiated as juveniles to single doses of 0.56, 1.13, 2.00, or 2.25 Gy. Blood lymphocytes (and skin fibroblasts from one individual) were obtained for cytogenetic analysis in 1993, near the end of the animals' lifespans. Results show identical dose-response relationships 28 y after exposure in vivo and immediately after exposure in vitro. Because chromosome aberrations are induced with identical frequencies in vivo and in vitro, these results demonstrate that the translocation frequencies induced in 1965 have not changed significantly during the almost three decades since exposure. Finally, our emerging biodosimetry data for individual radiation workers are now confirming the utility of reciprocal translocations measured by FISH in radiation dose reconstruction.

  14. Comparative anatomy of the arm muscles of the Japanese monkey (Macaca fuscata) with some comments on locomotor mechanics and behavior.

    PubMed

    Aversi-Ferreira, Tales Alexandre; Aversi-Ferreira, Roqueline A G M F; Bretas, Rafael Vieira; Nishimaru, Hiroshi; Nishijo, Hisao

    2016-08-01

    The anatomical literature on the genus Macaca has focused mainly on the rhesus monkey. However, some aspects in the positional behaviors of the Japanese monkey may be different from those in rhesus monkey, suggesting that the anatomical details of these species are divergent. Four thoracic limbs of Macaca fuscata adults were dissected. The arm muscles in Japanese macaques are more similar to rhesus monkeys and Papio; these characteristics are closer to those of bearded capuchins than apes, indicating more proximity of this genus to New World primates. The anatomical features observed favor quadrupedal locomotor behaviors on the ground and in arboreal environments. Japanese monkeys, rhesus monkeys, and bearded capuchins, which share more primitive characteristics in their arm muscles, present features that favor both arboreal and quadrupedal locomotor behaviors, whereas apes, mainly Pan and Gorilla, which spend more time on the ground, present more quadrupedal specializations. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. PCR detection and DNA sequence analysis of the regulatory region of lymphotropic papovavirus in peripheral blood mononuclear cells of an immunocompromised rhesus macaque

    NASA Technical Reports Server (NTRS)

    Lednicky, John A.; Halvorson, Steven J.; Butel, Janet S.

    2002-01-01

    A lymphotropic papovavirus (LPV) archetypal regulatory region was amplified from DNA from the blood of an immunocompromised rhesus monkey. We believe this is the first nonserological evidence of LPV infection in rhesus monkeys.

  16. Longitudinal analysis of behavioral, neurophysiological, viral and immunological effects of SIV infection in rhesus monkeys.

    PubMed

    Gold, L H; Fox, H S; Henriksen, S J; Buchmeier, M J; Weed, M R; Taffe, M A; Huitrón-Resendiz, S; Horn, T F; Bloom, F E

    1998-01-01

    A model is proposed in which a neurovirulent, microglial-passaged, simian immunodeficiency virus (SIV) is used to produce central nervous system (CNS) pathology and behavioral deficits in rhesus monkeys reminiscent of those seen in humans infected with human immunodeficiency virus (HIV). The time course of disease progression was characterized by using functional measures of cognition and motor skill, as well as neurophysiologic monitoring. Concomitant assessment of immunological and virological parameters illustrated correspondence between impaired behavioral performance and viral pathogenesis. Convergent results were obtained from neuropathological findings indicative of significant CNS disease. In ongoing studies, this SIV model is being used to explore the behavioral sequelae of immunodeficiency virus infection, the viral and host factors leading to neurologic dysfunction, and to begin testing potential therapeutic agents.

  17. Early Predictors of Impaired Social Functioning in Male Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Del Rosso, Laura A.; Seil, Shannon K.; Calonder, Laura A.; Madrid, Jesus E.; Bone, Kyle J.; Sherr, Elliott H.; Garner, Joseph P.; Capitanio, John P.; Parker, Karen J.

    2016-01-01

    Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1–4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys’ motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets

  18. Rhesus monkeys (Macaca mulatta) show robust primacy and recency in memory for lists from small, but not large, image sets.

    PubMed

    Basile, Benjamin M; Hampton, Robert R

    2010-02-01

    The combination of primacy and recency produces a U-shaped serial position curve typical of memory for lists. In humans, primacy is often thought to result from rehearsal, but there is little evidence for rehearsal in nonhumans. To further evaluate the possibility that rehearsal contributes to primacy in monkeys, we compared memory for lists of familiar stimuli (which may be easier to rehearse) to memory for unfamiliar stimuli (which are likely difficult to rehearse). Six rhesus monkeys saw lists of five images drawn from either large, medium, or small image sets. After presentation of each list, memory for one item was assessed using a serial probe recognition test. Across four experiments, we found robust primacy and recency with lists drawn from small and medium, but not large, image sets. This finding is consistent with the idea that familiar items are easier to rehearse and that rehearsal contributes to primacy, warranting further study of the possibility of rehearsal in monkeys. However, alternative interpretations are also viable and are discussed. Copyright 2009 Elsevier B.V. All rights reserved.

  19. Effect of daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys

    PubMed Central

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2015-01-01

    Opioid abusers discount delayed reinforcers more rapidly than non-users; however, it is unclear whether chronic drug administration or its discontinuation impact discounting. This study examined daily morphine administration and its discontinuation on delay discounting of food in rhesus monkeys. Responding on one lever delivered 1 food pellet immediately; responding on another lever delivered 2 food pellets either immediately or after a delay (30–120 sec) that increased within the session. Monkeys (n=3) responded for the large reinforcer when both reinforcers were delivered immediately and more for the smaller, immediately available reinforcer as delay to delivery of the large reinforcer increased. When administered acutely, morphine (0.032–5.6 mg/kg) increased trial omissions and had variable effects on choice, with small doses decreasing and large doses increasing choice of the large delayed reinforcer. Chronic morphine administration (0.1 mg/kg/day to 3.2 mg/kg twice daily) reduced choice of the large delayed reinforcer in two monkeys while increasing choice in a third monkey. Despite the development of tolerance to some effects (i.e., rightward shifts in dose-effect curves for the number of trials omitted) and evidence of mild opioid dependence (e.g., decrease in the number of trials completed as well as body weight), discontinuation of treatment did not appear to systematically impact discounting. Overall, these results suggest that repeated opioid administration causes persistent effects on choice under a delay discounting procedure; however, differences in the direction of effect among individuals suggest factors other than, or in addition to, changes in discounting might play a role. PMID:26397762

  20. Pioglitazone improves insulin action and normalizes menstrual cycles in a majority of prenatally androgenized female rhesus monkeys

    PubMed Central

    Zhou, Rao; Bruns, Cristin M.; Bird, Ian M.; Kemnitz, Joseph W.; Goodfriend, Theodore L.; Dumesic, Daniel A.; Abbott, David H.

    2009-01-01

    PURPOSE OF THE STUDY To determine whether pioglitazone will improve menstrual cyclicity in a fetal programming model for polycystic ovary syndrome. BASIC PROCEDURES Eight prenatally androgenized (PA) and 5 control female rhesus monkeys of similar age, body weight and body mass index received an oral placebo daily for 6–7 months followed, after at least 90 days, by daily oral dosing with pioglitazone (3mg/kg) for an additional 6–7 months. Blood was sampled thrice weekly to monitor ovulatory function, and a variety of endocrine challenges were performed to quantify changes in ovarian, gonadotropin and glucoregulatory function. MOST IMPORTANT FINDINGS Pioglitazone normalized menstrual cycles in 5 out of 8 (62%) PA females (pioglitazone responsive; PioRESP). Pioglitazone increased serum 17α-hydroxyprogesterone responses to an hCG injection in PioRESP PA females, while diminishing serum progesterone, and increasing DHEA and estradiol responses to hCG in PioRESP PA and all normal females. PRINCIPAL CONCLUSIONS Insulin resistance plays a mechanistic role in maintaining anovulation in a majority of PA female monkeys. PMID:17306503

  1. Effects of Foveal Ablation on the Pattern of Peripheral Refractive Errors in Normal and Form-deprived Infant Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Huang, Juan; Hung, Li-Fang

    2011-01-01

    Purpose. The purpose of this study was to determine whether visual signals from the fovea contribute to the changes in the pattern of peripheral refractions associated with form deprivation myopia in monkeys. Methods. Monocular form-deprivation was produced in 18 rhesus monkeys by securing diffusers in front of their treated eyes between 22 ± 2 and 155 ± 17 days of age. In eight of these form-deprived monkeys, the fovea and most of the perifovea of the treated eye were ablated by laser photocoagulation at the start of the diffuser-rearing period. Each eye's refractive status was measured by retinoscopy along the pupillary axis and at 15° intervals along the horizontal meridian to eccentricities of 45°. Control data were obtained from 12 normal monkeys and five monkeys that had monocular foveal ablations and were subsequently reared with unrestricted vision. Results. Foveal ablation, by itself, did not produce systematic alterations in either the central or peripheral refractive errors of the treated eyes. In addition, foveal ablation did not alter the patterns of peripheral refractions in monkeys with form-deprivation myopia. The patterns of peripheral refractive errors in the two groups of form-deprived monkeys, either with or without foveal ablation, were qualitatively similar (treated eyes: F = 0.31, P = 0.74; anisometropia: F = 0.61, P = 0.59), but significantly different from those found in the normal monkeys (F = 8.46 and 9.38 respectively, P < 0.05). Conclusions. Central retinal signals do not contribute in an essential way to the alterations in eye shape that occur during the development of vision-induced axial myopia. PMID:21693598

  2. Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hartvig, P.; Bergstroem, K.; Lindberg, B.

    1984-07-01

    The regional uptake in the brain of Rhesus monkeys of i.v. administered 11C-labeled morphine, codeine, heroin and pethidine was studied by means of positron emission tomography. The technique measures the sum of parent drug and radiolabeled metabolites. (For the sake of simplicity the drug derived radioactivity is denoted by the drug name.) Morphine had a limited uptake to discrete areas of the brain. The maximum normalized uptake, with respect to dose per kilogram body weight, was about 0.2, i.e., 20% of the calculated activity if the drug had been evenly distributed throughout the body of the monkey. Maximum radioactivity appearedmore » 30 to 45 min after injection. Morphine left the brain slowly with an estimated half-life of more than 2 hr. An area with a normalized uptake of about 1.0 was detected centrally in the lowest horizontal transsection of the skull. The origin of this area was identified as the pituitary. Codeine, heroin and pethidine were taken up to the brain to a larger extent than morphine, with maximum normalized uptakes of 2.6, 4.6 and 6.3, respectively. Maximum radioactivities of these drugs were achieved earlier and the elimination rates were faster than for morphine. Differences in the uptake of these drugs to the brain, as well as differences in time to maximal normalized uptake and rate of disappearance are considered to reflect differences in the lipophilic character between the drugs. Pethidine had the most rapid and extensive uptake followed by heroin, codeine and morphine in order of decreasing lipophilicity.« less

  3. Potassium transport in monkey erythrocytes.

    PubMed

    Stewart, G W; Blackstock, E J; Hall, A C; Ellory, J C

    1989-01-01

    K transport in Rhesus and Cynomolgus monkey erythrocytes has been characterised and compared to that in human erythrocytes. Transport due to the NaK pump, residual (diffusional) leak, volume-, pressure- and N-ethyl-maleimide-stimulated KCl system and internal Ca2+-stimulated K channel were similar to that in man but in the monkey it differed, in lacking the loop-diuretic-sensitive NaKCl cotransport system.

  4. Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys

    PubMed Central

    Banks, Matthew L.; Smith, Douglas A.; Blough, Bruce E.

    2016-01-01

    The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate ‘agonist’ medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like ‘agonist’ effects remains unknown. The present aim was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. Potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, ≥90%, methamphetamine-like effects. 2R,3R-hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like ‘agonist’ effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out. PMID:26886209

  5. Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys.

    PubMed

    Banks, Matthew L; Smith, Douglas A; Blough, Bruce E

    2016-04-01

    The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like 'agonist' effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like 'agonist' effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out.

  6. Cognitive imitation in 2-year-old children (Homo sapiens): a comparison with rhesus monkeys (Macaca mulatta).

    PubMed

    Subiaul, Francys; Romansky, Kathryn; Cantlon, Jessica F; Klein, Tovah; Terrace, Herbert

    2007-10-01

    Here we compare the performance of 2-year-old human children with that of adult rhesus macaques on a cognitive imitation task. The task was to respond, in a particular order, to arbitrary sets of photographs that were presented simultaneously on a touch sensitive video monitor. Because the spatial position of list items was varied from trial to trial, subjects could not learn this task as a series of specific motor responses. On some lists, subjects with no knowledge of the ordinal position of the items were given the opportunity to learn the order of those items by observing an expert model. Children, like monkeys, learned new lists more rapidly in a social condition where they had the opportunity to observe an experienced model perform the list in question, than under a baseline condition in which they had to learn new lists entirely by trial and error. No differences were observed between the accuracy of each species' responses to individual items or in the frequencies with which they made different types of errors. These results provide clear evidence that monkeys and humans share the ability to imitate novel cognitive rules (cognitive imitation).

  7. Head and neck resonance in a rhesus monkey - a comparison with results from a human model

    NASA Astrophysics Data System (ADS)

    Tinniswood, Adam; Gandhi, Om P.

    1999-03-01

    The use of primates for examining the effects of electromagnetic radiation on behavioural patterns is well established. Rats have also been used for this purpose. However, the monkey is of greater interest as its physiological make-up is somewhat closer to that of the human. Since the behavioural effects are likely to occur at lower field strengths for resonant absorption conditions for the head and neck, the need for determination of resonance frequencies for this region is obvious. Numerical techniques are ideal for the prediction of coupling to each of the organs, and accurate anatomically based models can be used to pinpoint the conditions for maximum absorption in the head in order to focus the experiments. In this paper we use two models, one of a human male and the other of a rhesus monkey, and find the mass-averaged power absorption spectra for both. The frequencies at which highest absorption (i.e. resonance) occurs in both the whole body and the head and neck region are determined. The results from these two models are compared for both E-polarization and k-polarization, and are shown to obey basic electromagnetic scaling principles.

  8. Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

    PubMed Central

    Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

    2014-01-01

    Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

  9. Reproducibility of carbachol stimulated accommodation in rhesus monkeys.

    PubMed

    Wendt, Mark; Glasser, Adrian

    2012-06-01

    Approaches are being explored to restore accommodation to the presbyopic eye. Some of these approaches can be tested in monkeys by stimulating accommodation in various ways including using carbachol iontophoresis. Knowledge of the repeatability of carbachol iontophoresis stimulated accommodation in the monkey phakic eye is necessary to understand the variability of this method of evaluating accommodation. Data from 9 to 10 separate carbachol iontophoresis experiments performed on phakic eyes from 8 monkeys were retrospectively analyzed. For each experiment, carbachol was applied iontophoretically to the eyes of anesthetized monkeys and refraction generally measured every two minutes until accommodation reached a plateau. Repeated experiments were performed in each monkey over periods ranging from 10 to 18 months. Maximum accommodation measured for each monkey ranged from 11.1 D to 18.3 D with standard deviations from 0.8 D to 2.1 D and differences in accommodative amplitude varying from 2.2 D to 7.5 D. Time to reach maximum accommodation ranged from 18 to 64 min in individual experiments. Averaged time-courses indicate that maximum accommodation is generally achieved between 10 and 20 min after carbachol administration. Although carbachol iontophoresis is considered a reliable method to stimulate maximum accommodation in anesthetized monkeys, the amplitude achieved typically varies by more than 2 D. Presbyopia treatments evaluated in this way in phakic monkeys would need to show an increase in accommodation of over 2 D to clearly demonstrate that the treatments work when being tested with carbachol iontophoresis stimulation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  10. The quantification of blood-brain barrier disruption using dynamic contrast-enhanced magnetic resonance imaging in aging rhesus monkeys with spontaneous type 2 diabetes mellitus.

    PubMed

    Xu, Ziqian; Zeng, Wen; Sun, Jiayu; Chen, Wei; Zhang, Ruzhi; Yang, Zunyuan; Yao, Zunwei; Wang, Lei; Song, Li; Chen, Yushu; Zhang, Yu; Wang, Chunhua; Gong, Li; Wu, Bing; Wang, Tinghua; Zheng, Jie; Gao, Fabao

    2017-09-01

    Microvascular lesions of the body are one of the most serious complications that can affect patients with type 2 diabetes mellitus. The blood-brain barrier (BBB) is a highly selective permeable barrier around the microvessels of the brain. This study investigated BBB disruption in diabetic rhesus monkeys using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Multi-slice DCE-MRI was used to quantify BBB permeability. Five diabetic monkeys and six control monkeys underwent magnetic resonance brain imaging in 3 Tesla MRI system. Regions of the frontal cortex, the temporal cortex, the basal ganglia, the thalamus, and the hippocampus in the two groups were selected as regions of interest to calculate the value of the transport coefficient K trans using the extended Tofts model. Permeability in the diabetic monkeys was significantly increased as compared with permeability in the normal control monkeys. Histopathologically, zonula occludens protein-1 decreased, immunoglobulin G leaked out of the blood, and nuclear factor E2-related factor translocated from the cytoplasm to the nuclei. It is likely that diabetes contributed to the increased BBB permeability. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. (Ir)rational choices of humans, rhesus macaques, and capuchin monkeys in dynamic stochastic environments.

    PubMed

    Watzek, Julia; Brosnan, Sarah F

    2018-05-28

    Human and animal decision-making is known to violate rational expectations in a variety of contexts. Previous models suggest that statistical structures of real-world environments can favor such seemingly irrational behavior, but this has not been tested empirically. We tested 16 capuchin monkeys, seven rhesus monkeys, and 30 humans in a computerized experiment that implemented such stochastic environments. Subjects chose from among up to three options of different value that disappeared and became available again with different probabilities. All species overwhelmingly chose transitively (A > B > C) in the control condition, where doing so maximized overall gain. Most subjects also adhered to transitivity in the test condition, where it was suboptimal, but ultimately led to negligible losses compared to the optimal, non-transitive strategy. We used a modelling approach to show that differences in temporal discounting may account for this pattern of choices on a proximate level. Specifically, when short- and long-term goals are valued similarly, near-optimal decision rules can map onto rational choice principles. Such cognitive shortcuts have been argued to have evolved to preserve mental resources without sacrificing good decision-making, and here we provide evidence that these heuristics can provide almost identical outcomes even in situations in which they lead to suboptimal choices. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. SURGICAL INTERVENTION AND ACCOMMODATIVE RESPONSES: I. CENTRIPETAL CILIARY BODY, CAPSULE AND LENS MOVEMENT IN RHESUS MONKEYS OF VARYING AGE

    PubMed Central

    Croft, Mary Ann; Mcdonald, Jared P.; James, Rebecca J.; Heatley, Gregg A.; Lin, Ting-Li; Lütjen-Drecoll, Elke; Kaufman, Paul L.

    2009-01-01

    Purpose To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. Methods In 18 rhesus monkey eyes (aged 6–27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal (E–W) nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extra-capsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis. Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Results Centripetal accommodative CP and capsule movement increased in velocity and amplitude post-ECLE compared to pre-ECLE regardless of age (n=5). The presence of the lens substance retarded capsule movement by ~21% in the young eyes and by ~62% in the older eyes. Post-ICLE compared to pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disturbed (n=7), but not in eyes in which the anterior vitreous was left intact (n=2). Following anterior regional zonulolysis (n=4), lens position shifted toward the lysed quadrant during accommodation. Conclusions The presence of the lens substance, capsule zonular attachments, and Wiegers ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce ~6 diopters of accommodation in the presence of a normal young crystalline lens or a similar surrogate. PMID:18552393

  13. Surgical intervention and accommodative responses, I: centripetal ciliary body, capsule, and lens movements in rhesus monkeys of various ages.

    PubMed

    Croft, Mary Ann; McDonald, Jared P; James, Rebecca J; Heatley, Gregg A; Lin, Ting-Li; Lütjen-Drecoll, Elke; Kaufman, Paul L

    2008-12-01

    To determine how surgically altering the normal relationship between the lens and the ciliary body in rhesus monkeys affects centripetal ciliary body and lens movement. In 18 rhesus monkey eyes (aged 6-27 years), accommodation was induced before and after surgery by electrical stimulation of the Edinger-Westphal nucleus. Accommodative amplitude was measured by coincidence refractometry. Goniovideography was performed before and after intra- and extracapsular lens extraction (ICLE, ECLE) and anterior regional zonulolysis (ARZ). Centripetal lens/capsule movements, centripetal ciliary process (CP) movements, and circumlental space were measured by computerized image analysis of the goniovideography images. Centripetal accommodative CP and capsule movement increased in velocity and amplitude after, compared with before, ECLE regardless of age (n = 5). The presence of the lens substance retarded capsule movement by approximately 21% in the young eyes and by approximately 62% in the older eyes. Post-ICLE compared with pre-ICLE centripetal accommodative CP movement was dampened in all eyes in which the anterior vitreous was disrupted (n = 7), but not in eyes in which the anterior vitreous was left intact (n = 2). After anterior regional zonulolysis (n = 4), lens position shifted toward the lysed quadrant during accommodation. The presence of the lens substance, capsule zonular attachments, and Wieger's ligament may play a role in centripetal CP movement. The capsule is still capable of centripetal movement in the older eye (although at a reduced capacity) and may have the ability to produce approximately 6 D of accommodation in the presence of a normal, young crystalline lens or a similar surrogate.

  14. Adenosine receptor distribution in Rhesus monkey ocular tissue.

    PubMed

    Beach, Krista M; Hung, Li-Fang; Arumugam, Baskar; Smith, Earl L; Ostrin, Lisa A

    2018-05-21

    Adenosine receptor (ADOR) antagonists, such as 7-methylxanthine (7-MX), have been shown to slow myopia progression in humans and animal models. Adenosine receptors are found throughout the body, and regulate the release of neurotransmitters such as dopamine and glutamate. However, the role of adenosine in eye growth is unclear. Evidence suggests that 7-MX increases scleral collagen fibril diameter, hence preventing axial elongation. This study used immunohistochemistry (IHC) and reverse-transcription quantitative polymerase chain reaction (RT-qPCR) to examine the distribution of the four ADORs in the normal monkey eye to help elucidate potential mechanisms of action. Eyes were enucleated from six Rhesus monkeys. Anterior segments and eyecups were separated into components and flash-frozen for RNA extraction or fixed in 4% paraformaldehyde and processed for immunohistochemistry against ADORA1, ADORA2a, ADORA2b, and ADORA3. RNA was reverse-transcribed, and qPCR was performed using custom primers. Relative gene expression was calculated using the ΔΔCt method normalizing to liver expression, and statistical analysis was performed using Relative Expression Software Tool. ADORA1 immunostaining was highest in the iris sphincter muscle, trabecular meshwork, ciliary epithelium, and retinal nerve fiber layer. ADORA2a immunostaining was highest in the corneal epithelium, trabecular meshwork, ciliary epithelium, retinal nerve fiber layer, and scleral fibroblasts. ADORA2b immunostaining was highest in corneal basal epithelium, limbal stem cells, iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells and scattered scleral fibroblasts. ADORA3 immunostaining was highest in the iris sphincter, ciliary muscle, ciliary epithelium, choroid, isolated retinal ganglion cells, and scleral fibroblasts. Compared to liver mRNA, ADORA1 mRNA was significantly higher in the brain, retina and choroid, and significantly lower in the iris/ciliary body. ADORA

  15. Rhesus monkey model of liver disease reflecting clinical disease progression and hepatic gene expression analysis

    PubMed Central

    Wang, Hong; Tan, Tao; Wang, Junfeng; Niu, Yuyu; Yan, Yaping; Guo, Xiangyu; Kang, Yu; Duan, Yanchao; Chang, Shaohui; Liao, Jianpeng; Si, Chenyang; Ji, Weizhi; Si, Wei

    2015-01-01

    Alcoholic liver disease (ALD) is a significant public health issue with heavy medical and economic burdens. The aetiology of ALD is not yet completely understood. The development of drugs and therapies for ALD is hampered by a lack of suitable animal models that replicate both the histological and metabolic features of human ALD. Here, we characterize a rhesus monkey model of alcohol-induced liver steatosis and hepatic fibrosis that is compatible with the clinical progression of the biochemistry and pathology in humans with ALD. Microarray analysis of hepatic gene expression was conducted to identify potential molecular signatures of ALD progression. The up-regulation of expression of hepatic genes related to liver steatosis (CPT1A, FASN, LEPR, RXRA, IGFBP1, PPARGC1A and SLC2A4) was detected in our rhesus model, as was the down-regulation of such genes (CYP7A1, HMGCR, GCK and PNPLA3) and the up-regulation of expression of hepatic genes related to liver cancer (E2F1, OPCML, FZD7, IGFBP1 and LEF1). Our results demonstrate that this ALD model reflects the clinical disease progression and hepatic gene expression observed in humans. These findings will be useful for increasing the understanding of ALD pathogenesis and will benefit the development of new therapeutic procedures and pharmacological reagents for treating ALD. PMID:26442469

  16. Metacognition in Monkeys during an Oculomotor Task

    ERIC Educational Resources Information Center

    Middlebrooks, Paul G.; Sommer, Marc A.

    2011-01-01

    This study investigated whether rhesus monkeys show evidence of metacognition in a reduced, visual oculomotor task that is particularly suitable for use in fMRI and electrophysiology. The 2-stage task involved punctate visual stimulation and saccadic eye movement responses. In each trial, monkeys made a decision and then made a bet. To earn…

  17. Microarray profiling of progesterone-regulated endometrial genes during the rhesus monkey secretory phase

    PubMed Central

    Ace, Christopher I; Okulicz, William C

    2004-01-01

    Background In the endometrium the steroid hormone progesterone (P), acting through its nuclear receptors, regulates the expression of specific target genes and gene networks required for endometrial maturation. Proper endometrial maturation is considered a requirement for embryo implantation. Endometrial receptivity is a complex process that is spatially and temporally restricted and the identity of genes that regulate receptivity has been pursued by a number of investigators. Methods In this study we have used high density oligonucleotide microarrays to screen for changes in mRNA transcript levels between normal proliferative and adequate secretory phases in Rhesus monkey artificial menstrual cycles. Biotinylated cRNA was prepared from day 13 and days 21–23 of the reproductive cycle and transcript levels were compared by hybridization to Affymetrix HG-U95A arrays. Results Of ~12,000 genes profiled, we identified 108 genes that were significantly regulated during the shift from a proliferative to an adequate secretory endometrium. Of these genes, 39 were up-regulated at days 21–23 versus day 13, and 69 were down-regulated. Genes up-regulated in P-dominant tissue included: secretoglobin (uteroglobin), histone 2A, polo-like kinase (PLK), spermidine/spermine acetyltransferase 2 (SAT2), secretory leukocyte protease inhibitor (SLPI) and metallothionein 1G (MT1G), all of which have been previously documented as elevated in the Rhesus monkey or human endometrium during the secretory phase. Genes down-regulated included: transforming growth factor beta-induced (TGFBI or BIGH3), matrix metalloproteinase 11 (stromelysin 3), proenkephalin (PENK), cysteine/glycine-rich protein 2 (CSRP2), collagen type VII alpha 1 (COL7A1), secreted frizzled-related protein 4 (SFRP4), progesterone receptor membrane component 1 (PGRMC1), chemokine (C-X-C) ligand 12 (CXCL12) and biglycan (BGN). In addition, many novel/unknown genes were also identified. Validation of array data was performed

  18. Resveratrol improves adipose insulin signaling and reduces the inflammatory response in adipose tissue of rhesus monkeys on high-fat, high-sugar diet.

    PubMed

    Jimenez-Gomez, Yolanda; Mattison, Julie A; Pearson, Kevin J; Martin-Montalvo, Alejandro; Palacios, Hector H; Sossong, Alex M; Ward, Theresa M; Younts, Caitlin M; Lewis, Kaitlyn; Allard, Joanne S; Longo, Dan L; Belman, Jonathan P; Malagon, Maria M; Navas, Placido; Sanghvi, Mitesh; Moaddel, Ruin; Tilmont, Edward M; Herbert, Richard L; Morrell, Christopher H; Egan, Josephine M; Baur, Joseph A; Ferrucci, Luigi; Bogan, Jonathan S; Bernier, Michel; de Cabo, Rafael

    2013-10-01

    Obesity is associated with a chronic, low-grade, systemic inflammation that may contribute to the development of insulin resistance and type 2 diabetes. Resveratrol, a natural compound with anti-inflammatory properties, is shown to improve glucose tolerance and insulin sensitivity in obese mice and humans. Here, we tested the effect of a 2-year resveratrol administration on proinflammatory profile and insulin resistance caused by a high-fat, high-sugar (HFS) diet in white adipose tissue (WAT) from rhesus monkeys. Resveratrol supplementation (80 and 480 mg/day for the first and second year, respectively) decreased adipocyte size, increased sirtuin 1 expression, decreased NF-κB activation, and improved insulin sensitivity in visceral, but not subcutaneous, WAT from HFS-fed animals. These effects were reproduced in 3T3-L1 adipocytes cultured in media supplemented with serum from monkeys fed HFS ± resveratrol diets. In conclusion, chronic administration of resveratrol exerts beneficial metabolic and inflammatory adaptations in visceral WAT from diet-induced obese monkeys. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Population variation in neuroendocrine activity is associated with behavioral inhibition and hemispheric brain structure in young rhesus monkeys

    PubMed Central

    Short, Sarah J.; Lubach, Gabriele R.; Shirtcliff, Elizabeth A.; Styner, Martin A.; Gilmore, John H.; Coe, Christopher L.

    2014-01-01

    Summary Population variation in hypothalamic-pituitary-adrenal (HPA) activity and reactivity was assessed in a healthy sample of 48 juvenile rhesus monkeys. Cluster analysis of the HPA profiles revealed four distinct neuroendocrine phenotypes based on six indices of HPA functioning. Behavioral reactivity was also evaluated in response to novel stimuli, and revealed marked differences between animals in the highest- and lowest-cortisol clusters. Specifically, animals in the high-cortisol cluster showed larger stress-induced cortisol responses and blunted feedback sensitivity to dexamethasone. They were also emotionally reactive, displayed more aggressive behaviors, and were less likely to approach novel objects. In contrast, monkeys in the low-cortisol cluster were more likely to approach and explore novel objects. Representative animals with high or low cortisol profiles were scanned with Magnetic Resonance Imaging to evaluate structural differences in global and regional gray matter (GM) and white matter (WM) volumes. Monkeys with higher cortisol reactivity evinced less hemispheric brain asymmetry, due to decreased GM in the right hemisphere. Stress reactivity was inversely related to global GM and positively related to total cerebrospinal fluid volume. This inverse relationship was also observed in several stress-sensitive regions, including prefrontal and frontal cortices. Our study demonstrates that population variation in pituitary-adrenal activity is related to behavioral disposition and cerebral structure in this nonhuman primate species. PMID:24954302

  20. Social relevance drives viewing behavior independent of low-level salience in rhesus macaques

    PubMed Central

    Solyst, James A.; Buffalo, Elizabeth A.

    2014-01-01

    Quantifying attention to social stimuli during the viewing of complex social scenes with eye tracking has proven to be a sensitive method in the diagnosis of autism spectrum disorders years before average clinical diagnosis. Rhesus macaques provide an ideal model for understanding the mechanisms underlying social viewing behavior, but to date no comparable behavioral task has been developed for use in monkeys. Using a novel scene-viewing task, we monitored the gaze of three rhesus macaques while they freely viewed well-controlled composed social scenes and analyzed the time spent viewing objects and monkeys. In each of six behavioral sessions, monkeys viewed a set of 90 images (540 unique scenes) with each image presented twice. In two-thirds of the repeated scenes, either a monkey or an object was replaced with a novel item (manipulated scenes). When viewing a repeated scene, monkeys made longer fixations and shorter saccades, shifting from a rapid orienting to global scene contents to a more local analysis of fewer items. In addition to this repetition effect, in manipulated scenes, monkeys demonstrated robust memory by spending more time viewing the replaced items. By analyzing attention to specific scene content, we found that monkeys strongly preferred to view conspecifics and that this was not related to their salience in terms of low-level image features. A model-free analysis of viewing statistics found that monkeys that were viewed earlier and longer had direct gaze and redder sex skin around their face and rump, two important visual social cues. These data provide a quantification of viewing strategy, memory and social preferences in rhesus macaques viewing complex social scenes, and they provide an important baseline with which to compare to the effects of therapeutics aimed at enhancing social cognition. PMID:25414633

  1. Transfer of hexachlorobenzene and polychlorinated biphenyls to nursing infant rhesus monkeys: enhanced toxicity

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bailey, J.; Knauf, V.; Mueller, W.

    Clophen A-30 (CA-30 or PCB) or hexachlorobenzene (HCB) were given daily by gavage to lactating rhesus monkeys for either 30 days (CA-30, 16 mg/kg/day) or 60 days (HCB, 64 mg/kg/day) to three infant-mother pairs per compound. The extent to which the CA-30 or HCB were concentreated in the milk of the mothers and consequently transferred to the nursing infants was determined by measuring concentrations of both substances in milk and serum samples collected at frequent intervals. One mother and all the infants from each group were sacrificed and the tissue content of HCB or PCBs measured. Milk concentrations averaged 20more » and 17 times higher than maternal serum levels for CA-300 and HCB-treated monkeys, respectively. Infant serum levels were approximately two to three (PCBs)-or two to five (HCB)-fold higher than serum concentrations in their mothers. All of the HCB-treated mothers remained healthy during dosing but one infant became moribund and was sacrificed on Day 22, and another died on Day 38. One CA-30-treated infant-mother pair was sacrificed on Day 23 of the study when they developed severe symptoms of poisoning. In general tissue levels of both HCB and Ca-30 were higher in the infants than in their mothers. Both HCB and PCB were concentrated in the infant fat, bone marrow, and adrenals. These findings are consistent with the hypothesis that nursing infants are at greater risk than their mothers when the mothers are exposed to lipophilic toxins.« less

  2. Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

    PubMed

    Dean, Brian; Arison, Byron; Chang, Steve; Thomas, Paul E; King, Christopher

    2004-06-01

    Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

  3. Development of a cerebrospinal fluid lateral reservoir model in rhesus monkeys (Macaca mulatta).

    PubMed

    Lester McCully, Cynthia M; Bacher, John; MacAllister, Rhonda P; Steffen-Smith, Emilie A; Saleem, Kadharbatcha; Thomas, Marvin L; Cruz, Rafael; Warren, Katherine E

    2015-02-01

    Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection. The FR model is associated with an intensive, prolonged recovery and frequent postsurgical hydrocephalus and nonpatency, whereas the LP model is associated with an easier recovery. To maximize the advantages of both systems, we developed the CSF lateral reservoir model (LR), which combines the beneficial features of the 2 previous models but avoids their limitations by using a reservoir for circulating CSF flow combined with catheter placement in the lateral ventricle. Nine adult male rhesus monkeys were utilized in this study. Pre-surgical MRI was performed to determine the coordinates of the lateral ventricle and location of choroid plexus (CP). The coordinates were determined to avoid the CP and major blood vessels. The predetermined coordinates were 100% accurate, according to MRI validation. The LR system functioned successfully in 67% of cases for 221 d, and 44% remain functional at 426 to 510 d postoperatively. Compared with established models, our LR model markedly reduced postoperative complications and recovery time. Development of the LR model was successful in rhesus macaques and is a useful alternative to the FR and LP methods of CSF collection from nonhuman primates.

  4. Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys.

    PubMed

    Barouch, Dan H; O'Brien, Kara L; Simmons, Nathaniel L; King, Sharon L; Abbink, Peter; Maxfield, Lori F; Sun, Ying-Hua; La Porte, Annalena; Riggs, Ambryice M; Lynch, Diana M; Clark, Sarah L; Backus, Katherine; Perry, James R; Seaman, Michael S; Carville, Angela; Mansfield, Keith G; Szinger, James J; Fischer, Will; Muldoon, Mark; Korber, Bette

    2010-03-01

    The worldwide diversity of HIV-1 presents an unprecedented challenge for vaccine development. Antigens derived from natural HIV-1 sequences have elicited only a limited breadth of cellular immune responses in nonhuman primate studies and clinical trials to date. Polyvalent 'mosaic' antigens, in contrast, are designed to optimize cellular immunologic coverage of global HIV-1 sequence diversity. Here we show that mosaic HIV-1 Gag, Pol and Env antigens expressed by recombinant, replication-incompetent adenovirus serotype 26 vectors markedly augmented both the breadth and depth without compromising the magnitude of antigen-specific T lymphocyte responses as compared with consensus or natural sequence HIV-1 antigens in rhesus monkeys. Polyvalent mosaic antigens therefore represent a promising strategy to expand cellular immunologic vaccine coverage for genetically diverse pathogens such as HIV-1.

  5. Long-term mortality and cancer risk in irradiated rhesus monkeys

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wood, D.H.

    1991-05-01

    Continuous, 24-year observations on a group of 358 rhesus monkeys reveal that life shortening from exposure to protons in the energy range encountered in the Van Allen belts and solar proton events is influenced primarily by the dose rather than by the energy of radiation. Life shortening in groups exposed to similar surface doses of 138- to 2300-MeV and 32- to 55-MeV protons are not significantly different, but the low-energy protons are associated with more deaths in the early years, while the high-energy protons contribute more to mortality in later years. In males, the most significant cause of life shorteningmore » is nonleukemia cancers. In females, radiation increased the risk of endometriosis (an abnormal proliferation of the lining of the uterus) which resulted in significant mortality in the years before early detection and treatment methods were employed. Animals exposed to 55-MeV protons had a high incidence of malignant brain tumors with latent periods ranging from 13 months to 20 years. The first fatal cancer among nonirradiated controls occurred 18 years after the study began. Analysis of the dose-response data supports the 1989 guidelines of the NCRP for maximum permissible radiation exposures in astronauts (NCRP, Guidance on Radiation Received in Space Activities, Report No. 98, National Council on Radiation Protection and Measurements, Bethesda, MD, 1989).« less

  6. Short- and Long-Term Clinical Outcomes in Rhesus Monkeys Inoculated with a Highly Pathogenic Chimeric Simian/Human Immunodeficiency Virus

    PubMed Central

    Endo, Yasuyuki; Igarashi, Tatsuhiko; Nishimura, Yoshiaki; Buckler, Charles; Buckler-White, Alicia; Plishka, Ronald; Dimitrov, Dimiter S.; Martin, Malcolm A.

    2000-01-01

    A highly pathogenic simian/human immunodeficiency virus (SHIV), SHIVDH12R, isolated from a rhesus macaque that had been treated with anti-human CD8 monoclonal antibody at the time of primary infection with the nonpathogenic, molecularly cloned SHIVDH12, induced marked and rapid CD4+ T cell loss in all rhesus macaques intravenously inoculated with 1.0 50% tissue culture infective dose (TCID50) to 4.1 × 105 TCID50s of virus. Animals inoculated with 650 TCID50s of SHIVDH12R or more experienced irreversible CD4+ T lymphocyte depletion and developed clinical disease requiring euthanasia between weeks 12 and 23 postinfection. In contrast, the CD4+ T-cell numbers in four of five monkeys receiving 25 TCID50s of SHIVDH12R or less stabilized at low levels, and these surviving animals produced antibodies capable of neutralizing SHIVDH12R. In the fifth monkey, no recovery from the CD4+ T cell decline occurred, and the animal had to be euthanized. Viral RNA levels, subsequent to the initial peak of infection but not at peak viremia, correlated with the virus inoculum size and the eventual clinical course. Both initial infection rate constants, k, and decay constants, d, were determined, but only the latter were statistically correlated to clinical outcome. The attenuating effects of reduced inoculum size were also observed when virus was inoculated by the mucosal route. Because the uncloned SHIVDH12R stock possessed the genetic properties of a lentivirus quasispecies, we were able to assess the evolution of the input virus swarm in animals surviving the acute infection by monitoring the emergence of neutralization escape viral variants. PMID:10888632

  7. Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Slikker, W. Jr.; Bailey, J.R.; Newport, D.

    1982-11-01

    The synthetic estrogen component of many oral contraceptives, 17 alpha-ethynylestradiol-17 beta (EE2) and the naturally occurring estrogen, estradiol-17 beta (E2) were studied in four pregnant rhesus monkeys (71% term: 108-121 days gestational age). Under ketamine anesthesia, catheters were implanted in the maternal femoral artery and fetal interplacental artery. After simultaneous i.v. administration of (/sup 3/H)EE2-(/sup 14/C)E2 to the maternal animal, serial blood samples were drawn from both mother and fetus. The estrogens and metabolites were identified and quantified by the comigration of radioactivity with reference standards in several high-performance liquid chromatography systems and subsequent selective enzyme hydrolysis of the conjugates.more » Only estrone (E1), E1 sulfate, EE2 and EE2-3 sulfate were observed in the fetal circulation, whereas the major radiolabeled compounds in the maternal circulation consisted of the above plus E2, E1 glucuronide and EE2-3 glucuronide. In order to determine whether the placenta could convert E2 to its metabolite E1, the placentas of three term rhesus monkeys were perfused in situ via the umbilical artery with 120 ml (15 ml/min) of Hanks' balanced salt solution (pH 7.4) containing (/sup 3/H)E2. High-performance liquid chromatographic analysis of umbilical vein samples revealed that 96% of the E2 was metabolized to E1. These studies indicate that the placenta can metabolize the potent naturally occurring estrogen E2 to the less potent E1. In contrast, the synthetic estrogen EE2 does not undergo this placental metabolic conversion and thus enters the fetal circulation as the parent compound.« less

  8. Evaluation of monkey intraocular pressure by rebound tonometer

    PubMed Central

    Yu, Wenhan; Cao, Guiqun; Qiu, Jinghua; Ma, Jia; Li, Ni; Yu, Man; Yan, Naihong; Chen, Lei; Pang, Iok-Hou

    2009-01-01

    Purpose To evaluate the usefulness of the TonoVet™ rebound tonometer in measuring intraocular pressure (IOP) of monkeys. Methods The accuracy of the TonoVet™ rebound tonometer was determined in cannulated eyes of anesthetized rhesus monkeys where IOP was controlled by adjusting the height of a connected perfusate reservoir. To assess the applicability of the equipment through in vivo studies, the diurnal fluctuation of IOP and effects of IOP-lowering compounds were evaluated in monkeys. Results IOP readings generated by the TonoVet™ tonometer correlated very well with the actual pressure in the cannulated monkey eye. The linear correlation had a slope of 0.922±0.014 (mean±SEM, n=4), a y-intercept of 3.04±0.61, and a correlation coefficient of r2=0.97. Using this method, diurnal IOP fluctuation of the rhesus monkey was demonstrated. The tonometer was also able to detect IOP changes induced by pharmacologically active compounds. A single topical ocular instillation (15 μg) of the rho kinase inhibitor, H1152, produced a 5–6 mmHg reduction (p<0.001) in IOP, lasting at least 4 h. In addition, topical administration of Travatan®, a prostaglandin agonist, induced a small transient IOP increase (1.1 mmHg versus vehicle control; p=0.26) at 2 h after treatment followed by a pressure reduction at 23 h (−2.4 mmHg; p<0.05). Multiple daily dosing with the drug produced a persistent IOP-lowering effect. Three consecutive days of Travatan treatment produced ocular hypotension of −2.0 to −2.2 mmHg (p<0.05) the following day. Conclusions The rebound tonometer was easy to use and accurately measured IOP in the rhesus monkey eye. PMID:19898690

  9. Establishing a standardized dental record-keeping system for a small investigational colony of rhesus monkeys (Macaca mulatta).

    PubMed

    Gibson, B W; McGuffey, L; Raflo, C P; Niemiec, B A

    2008-02-01

    Dental hygiene is becoming an increasingly important component of quality health care for laboratory animals, especially non-human primates (NHPs). One key to a successful health care program is an effective and efficient record-keeping system. To standardize a dental hygiene program for a small colony of NHPs, we developed a dental recording chart specific for rhesus monkeys. This dental chart was developed using the modified Triadan system. This system numbers teeth across species according to location. An illustrative case report was presented to demonstrate the accurate record keeping and spatial relationship generated from this Old World NHP dental chart design. The development and implementation of a standardized dental chart, as part of a dental hygiene program will help minimize variables that may affect research data.

  10. Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys.

    PubMed

    Gerak, Lisa R; Collins, Gregory T; France, Charles P

    2016-12-01

    Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin 2C [5-hydroxytryptamine 2C (5-HT 2C )] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32-320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1-1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32-100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10-17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals. Copyright © 2016 by The American Society for Pharmacology

  11. Effects of Lorcaserin on Cocaine and Methamphetamine Self-Administration and Reinstatement of Responding Previously Maintained by Cocaine in Rhesus Monkeys

    PubMed Central

    Gerak, Lisa R.; Collins, Gregory T.

    2016-01-01

    Stimulant abuse is a serious public health issue for which there is no effective pharmacotherapy. The serotonin2C [5-hydroxytryptamine2C (5-HT2C)] receptor agonist lorcaserin decreases some abuse-related effects of cocaine in monkeys and might be useful for treating stimulant abuse. The current study investigated the effectiveness of lorcaserin to reduce self-administration of either cocaine or methamphetamine and cocaine-induced reinstatement of extinguished responding. Four rhesus monkeys responded under a progressive-ratio (PR) schedule in which the response requirement increased after each cocaine infusion (32–320 μg/kg/infusion). A separate group of four monkeys responded under a fixed-ratio (FR) schedule for cocaine (32 μg/kg/infusion) and reinstatement of extinguished responding was examined following administration of noncontingent infusions of cocaine (0.1–1 mg/kg) that were combined with response-contingent presentations of the drug-associated stimuli. Finally, three monkeys responded under a FR schedule for methamphetamine (0.32–100 μg/kg/infusion). Lorcaserin (3.2 mg/kg) significantly decreased the final ratio completed (i.e., decreased break point) in monkeys responding under the PR schedule and reduced the reinstatement of responding for drug-associated stimuli following a noncontingent infusion of cocaine; these effects did not appear to change when lorcaserin was administered daily. The same dose of lorcaserin decreased responding for methamphetamine in two of the three monkeys, and the effect was maintained during daily lorcaserin administration; larger doses given acutely (10–17.8 mg/kg) significantly decreased responding for methamphetamine, although that effect was not sustained during daily lorcaserin administration. Together, these results indicate that lorcaserin might be effective in reducing cocaine and methamphetamine abuse and cocaine relapse at least in some individuals. PMID:27650954

  12. In vitro and in vivo metabolism of a novel cannabinoid-1 receptor inverse agonist, taranabant, in rats and monkeys.

    PubMed

    Reddy, V B G; Doss, G A; Karanam, B V; Samuel, K; Lanza, T J; Lin, L S; Yu, N X; Zhang, A S; Raab, C E; Stearns, R A; Kumar, S

    2010-09-01

    The metabolism and excretion of taranabant (MK-0364, N-[(1S,2S)-3-(4-chlorophenyl)-2-(3-cyanophenyl)-1-methylpropyl]-2-methyl-2{[5-(trifluoromethyl)pyridine-2-yl]oxy}propanamide), a potent cannabinoid-1 receptor inverse agonist, were evaluated in rats and rhesus monkeys. Following administration of [¹⁴C]taranabant, the majority of the radioactivity was excreted within 72 h. In both rats and rhesus monkeys, taranabant was eliminated primarily via oxidative metabolism, followed by excretion of metabolites into bile. Major pathways of metabolism that were common to rats and rhesus monkeys included hydroxylation at the benzylic carbon adjacent to the cyanophenyl ring to form a biologically active circulating metabolite M1, and oxidation of one of the two geminal methyl groups of taranabant or M1 to the corresponding diastereomeric carboxylic acids. Oxidation of the cyanophenyl ring, followed by conjugation with glutathione or glucuronic acid, was a major pathway of metabolism only in the rat and was not detected in the rhesus monkey. Metabolism profiles of taranabant in liver microsomes in vitro were qualitatively similar in rats, rhesus monkeys and humans and included formation of M1 and oxidation of taranabant or M1 to the corresponding carboxylic acids via oxidation of a geminal methyl group. In human liver microsomes, metabolism of taranabant was mediated primarily by CYP3A4.

  13. A Behavioral Taxonomy of Loneliness in Humans and Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Capitanio, John P.; Hawkley, Louise C.; Cole, Steven W.; Cacioppo, John T.

    2014-01-01

    Social relationships endow health and fitness benefits, but considerable variation exists in the extent to which individuals form and maintain salutary social relationships. The mental and physical health effects of social bonds are more strongly related to perceived isolation (loneliness) than to objective social network characteristics. We sought to develop an animal model to facilitate the experimental analysis of the development of, and the behavioral and biological consequences of, loneliness. In Study 1, using a population-based sample of older adults, we examined how loneliness was influenced both by social network size and by the extent to which individuals believed that their daily social interactions reflected their own choice. Results revealed three distinct clusters of individuals: (i) individuals with large networks who believed they had high choice were lowest in loneliness, (ii) individuals with small social networks who believed they had low choice were highest in loneliness, and (iii) the remaining two groups were intermediate and equivalent in loneliness. In Study 2, a similar three-group structure was identified in two separate samples of adult male rhesus monkeys (Macaca mulatta) living in large social groups: (i) those high in sociability who had complex social interaction with a broad range of social partners (putatively low in loneliness), (ii) those low in sociability who showed tentative interactions with certain classes of social partners (putatively high in loneliness), and (iii) those low in sociability who interacted overall at low levels with a broad range of social partners (putatively low or intermediate in loneliness). This taxonomy in monkeys was validated in subsequent experimental social probe studies. These results suggest that, in highly social nonhuman primate species, some animals may show a mismatch between social interest and social attainment that could serve as a useful animal model for experimental and mechanistic

  14. Sub-chronic inhalation of high concentrations of manganese sulfate induces lower airway pathology in rhesus monkeys

    PubMed Central

    Dorman, David C; Struve, Melanie F; Gross, Elizabeth A; Wong, Brian A; Howroyd, Paul C

    2005-01-01

    Background Neurotoxicity and pulmonary dysfunction are well-recognized problems associated with prolonged human exposure to high concentrations of airborne manganese. Surprisingly, histological characterization of pulmonary responses induced by manganese remains incomplete. The primary objective of this study was to characterize histologic changes in the monkey respiratory tract following manganese inhalation. Methods Subchronic (6 hr/day, 5 days/week) inhalation exposure of young male rhesus monkeys to manganese sulfate was performed. One cohort of monkeys (n = 4–6 animals/exposure concentration) was exposed to air or manganese sulfate at 0.06, 0.3, or 1.5 mg Mn/m3 for 65 exposure days. Another eight monkeys were exposed to manganese sulfate at 1.5 mg Mn/m3 for 65 exposure days and held for 45 or 90 days before evaluation. A second cohort (n = 4 monkeys per time point) was exposed to manganese sulfate at 1.5 mg Mn/m3 and evaluated after 15 or 33 exposure days. Evaluations included measurement of lung manganese concentrations and evaluation of respiratory histologic changes. Tissue manganese concentrations were compared for the exposure and control groups by tests for homogeneity of variance, analysis of variance, followed by Dunnett's multiple comparison. Histopathological findings were evaluated using a Pearson's Chi-Square test. Results Animals exposed to manganese sulfate at ≥0.3 mg Mn/m3 for 65 days had increased lung manganese concentrations. Exposure to manganese sulfate at 1.5 mg Mn/m3 for ≥15 exposure days resulted in increased lung manganese concentrations, mild subacute bronchiolitis, alveolar duct inflammation, and proliferation of bronchus-associated lymphoid tissue. Bronchiolitis and alveolar duct inflammatory changes were absent 45 days post-exposure, suggesting that these lesions are reversible upon cessation of subchronic high-dose manganese exposure. Conclusion High-dose subchronic manganese sulfate inhalation is associated with increased

  15. Hematologic and lymphocyte immunophenotypic reference values for normal rhesus monkey (Macaca mulatta) umbilical cord blood; gravidity may play a role in study design.

    PubMed

    Rogers, Linda B; Kaack, M Bernice; Henson, Michael C; Rasmussen, Terri; Henson, Elizabeth; Veazey, Ronald S; Krogstad, Donald J; Davison, Billie B

    2005-06-01

    Hematology and flow cytometry reference values for rhesus umbilical cord blood (UCB) were established in 17 healthy infant rhesus monkeys delivered by elective cesarean section 10 days preterm. The infants were born to age matched, singly caged primigravid or secundigravid dams. The hematology and flow cytometry values were determined by automated cell counter and by FACS. No significant differences were observed with respect to infant gender. With respect to gravida, the primigravid infants had a significantly higher percentage (P= 0.05) of CD20(+) B lymphocytes in UCB. These results provide useful reference values for future studies of maternal - fetal disease transmission, vaccine and drug evaluation in non-human primate pregnancy, as well as fetal programming and immune modulation, gene therapy and the use of UCB as a source of stem cells for research and transplantation. Importantly, our results suggest that maternal gravidity may be an important variable to consider.

  16. Development of an apparatus and methodology for conducting functional magnetic resonance imaging (fMRI) with pharmacological stimuli in conscious rhesus monkeys.

    PubMed

    Murnane, Kevin Sean; Howell, Leonard Lee

    2010-08-15

    Functional magnetic resonance imaging (fMRI) is a technique with significant potential to advance our understanding of multiple brain systems. However, when human subjects undergo fMRI studies they are typically conscious whereas pre-clinical fMRI studies typically utilize anesthesia, which complicates comparisons across studies. Therefore, we have developed an apparatus suitable for imaging conscious rhesus monkeys. In order to minimize subject stress and spatial motion, each subject was acclimated to the necessary procedures over several months. The effectiveness of this process was then evaluated, in fully trained subjects, by quantifying objective physiological measures. These physiological metrics were stable both within and across sessions and did not differ from when these same subjects were immobilized using standard primate handling procedures. Subject motion and blood oxygenation level dependent (BOLD) fMRI measurements were then evaluated by scanning subjects under three different conditions: the absence of stimulation, presentation of a visual stimulus, or administration of intravenous (i.v.) cocaine (0.3mg/kg). Spatial motion differed neither by condition nor along the three principal axes. In addition, maximum translational and rotational motion never exceeded one half of the voxel size (0.75 mm) or 1.5 degrees, respectively. Furthermore, the localization of changes in blood oxygenation closely matched those reported in previous studies using similar stimuli. These findings document the feasibility of fMRI data collection in conscious rhesus monkeys using these procedures and allow for the further study of the neural effects of psychoactive drugs. (c) 2010 Elsevier B.V. All rights reserved.

  17. Mathematical modeling of serum 13C-retinol in captive rhesus monkeys provides new insights on hypervitaminosis A.

    PubMed

    Escaron, Anne L; Green, Michael H; Howe, Julie A; Tanumihardjo, Sherry A

    2009-10-01

    Hypervitaminosis A is increasingly a public health concern, and thus noninvasive quantitative methods merit exploration. In this study, we applied the (13)C-retinol isotope dilution test to a nonhuman primate model with excessive liver stores. After baseline serum chemistries, rhesus macaques (Macaca mulatta; n = 16) were administered 3.5 mumol (13)C(2)-retinyl acetate. Blood was drawn at baseline, 5 h, and 2, 4, 7, 14, 21, and 28 d following the dose. Liver biopsies were collected 7 d before and 2 d after dosing (n = 4) and at 7, 14, and 28 d (n = 4/time) after dosing. Serum and liver were analyzed by HPLC and GC-combustion-isotope ratio MS for retinol and its enrichment, respectively. Model-based compartmental analysis was applied to serum data. Lactate dehydrogenase was elevated in 50% of the monkeys. Total body reserves (TBR) of vitamin A (VA) were calculated at 28 d. Predicted TBR (3.52 +/- 2.01 mmol VA) represented measured liver stores (4.56 +/- 1.38 mmol VA; P = 0.124). Predicted liver VA concentrations (13.3 +/- 9.7 micromol/g) were similar to measured liver VA concentrations (16.4 +/- 5.3 micromol/g). The kinetic models predict that 27-52% of extravascular VA is exchanging with serum in hypervitaminotic A monkeys. The test correctly diagnosed hypervitaminosis A in all monkeys, i.e. 100% sensitivity. Stable isotope techniques have important public health potential for the classification of VA status, including hypervitaminosis, because no other technique besides invasive liver biopsies, correctly identifies excessive liver VA stores.

  18. Quantitative assessment of timing, efficiency, specificity and genetic mosaicism of CRISPR/Cas9-mediated gene editing of hemoglobin beta gene in rhesus monkey embryos.

    PubMed

    Midic, Uros; Hung, Pei-Hsuan; Vincent, Kailey A; Goheen, Benjamin; Schupp, Patrick G; Chen, Diane D; Bauer, Daniel E; VandeVoort, Catherine A; Latham, Keith E

    2017-07-15

    Gene editing technologies offer new options for developing novel biomedical research models and for gene and stem cell based therapies. However, applications in many species demand high efficiencies, specificity, and a thorough understanding of likely editing outcomes. To date, overall efficiencies, rates of off-targeting and degree of genetic mosaicism have not been well-characterized for most species, limiting our ability to optimize methods. As a model gene for measuring these parameters of the CRISPR/Cas9 application in a primate species (rhesus monkey), we selected the β-hemoglobin gene (HBB), which also has high relevance to the potential application of gene editing and stem-cell technologies for treating human disease. Our data demonstrate an ability to achieve a high efficiency of gene editing in rhesus monkey zygotes, with no detected off-target effects at selected off-target loci. Considerable genetic mosaicism and variation in the fraction of embryonic cells bearing targeted alleles are observed, and the timing of editing events is revealed using a new model. The uses of Cas9-WT protein combined with optimized concentrations of sgRNAs are two likely areas for further refinement to enhance efficiency while limiting unfavorable outcomes that can be exceedingly costly for application of gene editing in primate species. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  19. Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys.

    PubMed

    Koffarnus, Mikhail N; Winger, Gail

    2015-07-01

    The relatively weak reinforcing effects of nicotine in experimental studies have been attributed to possible aversive effects or the need to space nicotine administrations over time to expose reinforcing effects. This study was designed to determine if the response-maintaining effects of nicotine are increased when availability is spaced through time, and whether nicotine is an effective punisher of remifentanil-maintained responding. Compared to a cocaine reference dose, nicotine dose and timeout (TO) value were varied in eight rhesus monkeys responding for intravenous (i.v.) nicotine on varying fixed-ratio (FR) schedules of reinforcement.The aversive effects of nicotine were evaluated in four animals choosing between a standard dose of remifentanil alone or in combination with one of several doses of nicotine. In three of eight self-administration monkeys, 0.01 mg/kg/inj nicotine did not maintain responding at any FR value. In the other five animals, nicotine-maintained response rates increased with either FR or TO values to a certain point, and then slowed. Maximum nicotine-maintained response rates were much slower than those maintained by cocaine, and demand for nicotine was less than demand for cocaine. Nicotine was an effective punisher of remifentanil-maintained responding at doses ranging from 0.01 to 0.3 mg/kg/inj. Lower punishing dose seemed to be related to the absence of reinforcing effects within subject. There are an order of magnitude individual differences in sensitivity to both the reinforcing and punishing effects of nicotine, and this drug may be unique in being a weak positive reinforcer in small doses and aversive in large doses.

  20. Regulatory effect of Epithalon on production of melatonin and cortisol in old monkeys.

    PubMed

    Goncharova, N D; Khavinson, B K; Lapin, B A

    2001-04-01

    The effect of Epithalon on melatonin and cortisol secretion in female rhesus monkeys of various ages was evaluated by enzyme immunoassay. Epithalon stimulated evening melatonin production and normalized circadian rhythms of cortisol production in old monkeys.

  1. Lethal canine distemper virus outbreak in cynomolgus monkeys in Japan in 2008.

    PubMed

    Sakai, Kouji; Nagata, Noriyo; Ami, Yasushi; Seki, Fumio; Suzaki, Yuriko; Iwata-Yoshikawa, Naoko; Suzuki, Tadaki; Fukushi, Shuetsu; Mizutani, Tetsuya; Yoshikawa, Tomoki; Otsuki, Noriyuki; Kurane, Ichiro; Komase, Katsuhiro; Yamaguchi, Ryoji; Hasegawa, Hideki; Saijo, Masayuki; Takeda, Makoto; Morikawa, Shigeru

    2013-01-01

    Canine distemper virus (CDV) has recently expanded its host range to nonhuman primates. A large CDV outbreak occurred in rhesus monkeys at a breeding farm in Guangxi Province, China, in 2006, followed by another outbreak in rhesus monkeys at an animal center in Beijing in 2008. In 2008 in Japan, a CDV outbreak also occurred in cynomolgus monkeys imported from China. In that outbreak, 46 monkeys died from severe pneumonia during a quarantine period. A CDV strain (CYN07-dV) was isolated in Vero cells expressing dog signaling lymphocyte activation molecule (SLAM). Phylogenic analysis showed that CYN07-dV was closely related to the recent CDV outbreaks in China, suggesting continuing chains of CDV infection in monkeys. In vitro, CYN07-dV uses macaca SLAM and macaca nectin4 as receptors as efficiently as dog SLAM and dog nectin4, respectively. CYN07-dV showed high virulence in experimentally infected cynomolgus monkeys and excreted progeny viruses in oral fluid and feces. These data revealed that some of the CDV strains, like CYN07-dV, have the potential to cause acute systemic infection in monkeys.

  2. Immunocyte Response to Experimental Mumps Virus Infection in Rhesus Monkeys

    PubMed Central

    Genco, R. J.; Flanagan, T. D.; Emmings, F. G.

    1973-01-01

    Nineteen rhesus monkeys were inoculated with mumps virus by retrograde ductal instillation into the parotid gland. Evidence of infection was obtained in all instances. Virus was isolated from buccal swabbings and parotid biopsies for 1 week after inoculation. A vigorous serum-neutralizing antibody response occurred within 3 weeks, and there was marked monocytic infiltration of the parotid stroma. The monocytic infiltrate comprised as much as 60% of the total gland volume 1 week after infection. The predominant inflammatory cells were non-immunoglobulin-containing mononuclear cells resembling lymphocytes. Plasma cells containing immunoglobulin G (IgG), IgA, IgM, and IgE increased in numbers in the gland after infection, the greatest increase occurring in IgG-containing cells. Neutralizing antibodies and interferon were found in extracts prepared from the infected glands. Neutralizing activity was highest in samples taken 3 weeks after infection but was detectable in samples taken as soon as 36 to 48 h after infection. Interferon activity was detected in significant amounts 36 to 48 h after infection. Challenge of previously infected animals resulted in an increase in the monocytic infiltrate as well as an increase in numbers of immunoglobulin-containing plasma cells. However, reinfection did not occur as evidenced by the inability to culture shed virus after challenge. This model should be useful for in vivo study of biochemical mediators which evoke inflammatory cell infiltration and which may be significant both in protection and in tissue damage. PMID:4202659

  3. A subanesthetic dose of ketamine in the Rhesus monkey reduces the occurrence of anticipatory saccades.

    PubMed

    Ameqrane, Ilhame; Ilhame, Ameqrane; Wattiez, Nicolas; Nicolas, Wattiez; Pouget, Pierre; Pierre, Pouget; Missal, Marcus; Marcus, Missal

    2015-10-01

    It has been shown that antagonism of the glutamatergic N-methyl-D-aspartate (NMDA) receptor with subanesthetic doses of ketamine perturbs the perception of elapsed time. Anticipatory eye movements are based on an internal representation of elapsed time. Therefore, the occurrence of anticipatory saccades could be a particularly sensitive indicator of abnormal time perception due to NMDA receptors blockade. The objective of this study was to determine whether the occurrence of anticipatory saccades could be selectively altered by a subanesthetic dose of ketamine. Three Rhesus monkeys were trained in a simple visually guided saccadic task with a variable delay. Monkeys were rewarded for making a visually guided saccade at the end of the delay. Premature anticipatory saccades to the future position of the eccentric target initiated before the end of the delay were not rewarded. A subanesthetic dose of ketamine (0.25 mg/kg) or a saline solution of the same volume was injected i.m. during the task. We found that the injected dose of ketamine did not induce sedation or abnormal behavior. However, in ∼4 min, ketamine induced a strong reduction of the occurrence of anticipatory saccades but did not reduce the occurrence of visually guided saccades. This unexpected reduction of anticipatory saccade occurrence could be interpreted as resulting from an altered use of the perception of elapsed time during the delay period induced by NMDA receptors antagonism.

  4. Effects of formaldehyde gas on the respiratory tract of rhesus monkeys. Pathology and cell proliferation.

    PubMed Central

    Monticello, T. M.; Morgan, K. T.; Everitt, J. I.; Popp, J. A.

    1989-01-01

    Formaldehyde is a nasal carcinogen in rats but it remains to be determined what cancer risk this chemical poses in humans. Molecular dosimetry studies of formaldehyde and cellular proliferative responses to formaldehyde-induced cytotoxicity have been studied in the rodent and are important components of the authors' ongoing research, which has now been extended to nonhuman primates, a species more analogous to humans. The present study was designed to characterize formaldehyde injury in the respiratory tract of nonhuman primates to provide a direct comparison to the toxic effects of formaldehyde in rodents. Groups of three rhesus monkeys were exposed to room air, or 6 ppm formaldehyde for 5 days per week for 1 or 6 weeks, and the respiratory tract was assessed for nature and extent of histologic responses, and changes in epithelial cell proliferation rate. Lesions were characterized by mild degeneration and early squamous metaplasia confined to specific regions of the transitional and respiratory epithelia of the nasal passages and the respiratory epithelium of the trachea and major bronchi. There was minimal progression of histologic changes between 1 and 6 weeks; however, the percent of nasal surface area affected significantly increased in the 6-week exposure group. Formaldehyde-induced lesions were associated with increases in cell proliferation rates up to 18-fold over controls, which remained significantly elevated after 6 weeks of exposure. Histologic lesions and increases in cell proliferation were most extensive in the nasal passages and were minimal in the lower airways, whereas the maxillary sinuses exhibited no evidence of a response to formaldehyde exposure. Based on the extent of lesions and cell proliferation data, it appears that the monkey is more sensitive than the rat to the acute and subacute effects of formaldehyde at 6 ppm. The absence of response in the maxillary sinuses in the monkey suggests that combining tumors of the nasal cavity and

  5. Control of Working Memory in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Tu, Hsiao-Wei; Hampton, Robert R.

    2014-01-01

    Cognitive control is critical for efficiently using the limited resources in working memory. It is well established that humans use rehearsal to increase the probability of remembering needed information, but little is known in nonhumans, with some studies reporting the absence of active control and others subject to alternative explanations. We trained monkeys in a visual matching-to-sample paradigm with a post-sample memory cue. Monkeys either saw a remember cue that predicted the occurrence of a matching test that required memory for the sample, or a forget cue that predicted a discrimination test that did not require memory of the sample. Infrequent probe trials on which monkeys were given tests of the type not cued on that trial were used to assess whether memory was under cognitive control. Our procedures controlled for reward expectation and for the surprising nature of the probes. Monkeys matched less accurately after forget cues, while discrimination accuracy was equivalent in the two cue conditions. We also tested monkeys with lists of two consecutive sample images that shared the same cue. Again, memory for expected memory tests was superior to that on unexpected tests. Together these results show that monkeys cognitively control their working memory. PMID:25436219

  6. Short-term testosterone manipulations do not affect cognition or motor function but differentially modulate emotions in young and older male rhesus monkeys.

    PubMed

    Kelly, Brian; Maguire-Herring, Vanessa; Rose, Christian M; Gore, Heather E; Ferrigno, Stephen; Novak, Melinda A; Lacreuse, Agnès

    2014-11-01

    Human aging is characterized by declines in cognition and fine motor function as well as improved emotional regulation. In men, declining levels of testosterone (T) with age have been implicated in the development of these age-related changes. However, studies examining the effects of T replacement on cognition, emotion and fine motor function in older men have not provided consistent results. Rhesus monkeys (Macaca mulatta) are excellent models for human cognitive aging and may provide novel insights on this issue. We tested 10 aged intact male rhesus monkeys (mean age=19, range 15-25) on a battery of cognitive, motor and emotional tasks at baseline and under low or high T experimental conditions. Their performance was compared to that of 6 young males previously tested in the same paradigm (Lacreuse et al., 2009; Lacreuse et al., 2010). Following a 4-week baseline testing period, monkeys were treated with a gonadotropin releasing hormone agonist (Depot Lupron, 200 μg/kg) to suppress endogenous T and were tested on the task battery under a 4-week high T condition (injection of Lupron+T enanthate, 20 mg/kg, n=8) or 4-week low T condition (injection of Lupron+oil vehicle, n=8) before crossing over to the opposite treatment. The cognitive tasks consisted of the Delayed Non-Matching-to-Sample (DNMS), the Delayed Response (DR), and the Delayed Recognition Span Test (spatial-DRST). The emotional tasks included an object Approach-Avoidance task and a task in which monkeys were played videos of unfamiliar conspecifics in different emotional context (Social Playbacks). The fine motor task was the Lifesaver task that required monkeys to remove a Lifesaver candy from rods of different complexity. T manipulations did not significantly affect visual recognition memory, working memory, reference memory or fine motor function at any age. In the Approach-Avoidance task, older monkeys, but not younger monkeys, spent more time in proximity of novel objects in the high T condition

  7. Developmental Increase in Kisspeptin-54 Release in Vivo Is Independent of the Pubertal Increase in Estradiol in Female Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Guerriero, Kathryn A.; Keen, Kim L.

    2012-01-01

    Kisspeptin (KP) signaling has been proposed as an important regulator in the mechanism of puberty. In this study, to determine the role of KP in puberty, we assessed the in vivo release pattern of KP-54 from the basal hypothalamus/stalk-median eminence in prepubertal and pubertal ovarian-intact female rhesus monkeys. We found that there was a developmental increase in mean KP-54 release, pulse frequency, and pulse amplitude, which is parallel to the developmental changes in GnRH release that we previously reported. Moreover, a nocturnal increase in KP-54 release becomes prominent after the onset of puberty. Because the pubertal increase in GnRH release occurs independent of the pubertal increase in circulating gonadal steroids, we further examined whether ovariectomy (OVX) modifies the release pattern of KP-54. Results show that OVX in pubertal monkeys enhanced mean KP-54 release and pulse amplitude but not pulse frequency, whereas OVX did not alter the release pattern of KP-54 in prepubertal monkeys. Estradiol replacement in OVX pubertal monkeys suppressed mean KP-54 release and pulse amplitude but not pulse frequency. Estradiol replacement in OVX prepubertal monkeys did not alter the KP-54 release pattern. Collectively these results suggest that the pubertal increase in KP release occurs independent of the pubertal increase in circulating estradiol. Nevertheless, the pubertal increase in KP release is not likely responsible for the initiation of the pubertal increase in GnRH release. Rather, after puberty onset, the increase in KP release contributes to further increase GnRH release during the progression of puberty. PMID:22315444

  8. Social Recovery of Monkeys Isolated for the First Year of Life: 1. Rehabilitation and Therapy

    ERIC Educational Resources Information Center

    Novak, M. A.; Harlow, H. F.

    1975-01-01

    This experiment demonstrated that 12-month-old monkeys reared in social isolation developed appropriate species-typical behavior through the use of adaptation, self pacing of visual input and exposure to younger "therapist" monkeys. A critical period of socialization is not indicated in the rhesus monkey. (GO)

  9. The response of neurons in areas V1 and MT of the alert rhesus monkey to moving random dot patterns.

    PubMed

    Snowden, R J; Treue, S; Andersen, R A

    1992-01-01

    We studied the response of single units to moving random dot patterns in areas V1 and MT of the alert macaque monkey. Most cells could be driven by such patterns; however, many cells in V1 did not give a consistent response but fired at a particular point during stimulus presentation. Thus different dot patterns can produce a markedly different response at any particular time, though the time averaged response is similar. A comparison of the directionality of cells in both V1 and MT using random dot patterns shows the cells of MT to be far more directional. In addition our estimates of the percentage of directional cells in both areas are consistent with previous reports using other stimuli. However, we failed to find a bimodality of directionality in V1 which has been reported in some other studies. The variance associated with response was determined for individual cells. In both areas the variance was found to be approximately equal to the mean response, indicating little difference between extrastriate and striate cortex. These estimates are in broad agreement (though the variance appears a little lower) with those of V1 cells of the anesthetized cat. The response of MT cells was simulated on a computer from the estimates derived from the single unit recordings. While the direction tuning of MT cells is quite wide (mean half-width at half-height approximately 50 degrees) it is shown that the cells can reliably discriminate much smaller changes in direction, and the performance of the cells with the smallest discriminanda were comparable to thresholds measured with human subjects using the same stimuli (approximately 1.1 degrees). Minimum discriminanda for individual cells occurred not at the preferred direction, that is, the peak of their tuning curves, but rather on the steep flanks of their tuning curves. This result suggests that the cells which may mediate the discrimination of motion direction may not be the cells most sensitive to that direction.

  10. Age-related changes in glial cells of dopamine midbrain subregions in rhesus monkeys.

    PubMed

    Kanaan, Nicholas M; Kordower, Jeffrey H; Collier, Timothy J

    2010-06-01

    Aging remains the strongest risk factor for developing Parkinson's disease (PD), and there is selective vulnerability in midbrain dopamine (DA) neuron degeneration in PD. By tracking normal aging-related changes with an emphasis on regional specificity, factors involved in selective vulnerability and resistance to degeneration can be studied. Towards this end, we sought to determine whether age-related changes in microglia and astrocytes in rhesus monkeys are region-specific, suggestive of involvement in regional differences in vulnerability to degeneration that may be relevant to PD pathogenesis. Gliosis in midbrain DA subregions was measured by estimating glia number using unbiased stereology, assessing fluorescence intensity for proteins upregulated during activation, and rating morphology. With normal aging, microglia exhibited increased staining intensity and a shift to more activated morphologies preferentially in the vulnerable substantia nigra-ventral tier (vtSN). Astrocytes did not exhibit age-related changes consistent with an involvement in regional vulnerability in any measure. Our results suggest advancing age is associated with chronic mild inflammation in the vtSN, which may render these DA neurons more vulnerable to degeneration. Copyright 2008 Elsevier Inc. All rights reserved.

  11. Rhesus monkeys employ a procedural strategy to reduce working memory load in a self-ordered spatial search task

    PubMed Central

    Taffe, Michael A.; Taffe, William J.

    2011-01-01

    Several nonhuman primate species have been reported to employ a distance-minimizing, traveling salesman-like, strategy during foraging as well as in experimental spatial search tasks involving lesser amounts of locomotion. Spatial sequencing may optimize performance by reducing reference or episodic memory loads, locomotor costs, competition or other demands. A computerized self-ordered spatial search (SOSS) memory task has been adapted from a human neuropsychological testing battery (CANTAB, Cambridge Cognition, Ltd) for use in monkeys. Accurate completion of a trial requires sequential responses to colored boxes in two or more spatial locations without repetition of a previous location. Marmosets have been reported to employ a circling pattern of search, suggesting spontaneous adoption of a strategy to reduce working memory load. In this study the SOSS performance of rhesus monkeys was assessed to determine if the use of a distance-minimizing search path enhances accuracy. A novel strategy score, independent of the trial difficulty and arrangement of boxes, has been devised. Analysis of the performance of 21 monkeys trained on SOSS over two years shows that a distance-minimizing search strategy is associated with improved accuracy. This effect is observed within individuals as they improve over many cumulative sessions of training on the task and across individuals at any given level of training. Erroneous trials were associated with a failure to deploy the strategy. It is concluded that the effect of utilizing the strategy on this locomotion-free, laboratory task is to enhance accuracy by reducing demands on spatial working memory resources. PMID:21840507

  12. Sequential responding and planning in capuchin monkeys (Cebus apella).

    PubMed

    Beran, Michael J; Parrish, Audrey E

    2012-11-01

    Previous experiments have assessed planning during sequential responding to computer generated stimuli by Old World nonhuman primates including chimpanzees and rhesus macaques. However, no such assessment has been made with a New World primate species. Capuchin monkeys (Cebus apella) are an interesting test case for assessing the distribution of cognitive processes in the Order Primates because they sometimes show proficiency in tasks also mastered by apes and Old World monkeys, but in other cases fail to match the proficiency of those other species. In two experiments, eight capuchin monkeys selected five arbitrary stimuli in distinct locations on a computer monitor in a learned sequence. In Experiment 1, shift trials occurred in which the second and third stimuli were transposed when the first stimulus was selected by the animal. In Experiment 2, mask trials occurred in which all remaining stimuli were masked after the monkey selected the first stimulus. Monkeys made more mistakes on trials in which the locations of the second and third stimuli were interchanged than on trials in which locations were not interchanged, suggesting they had already planned to select a location that no longer contained the correct stimulus. When mask trials occurred, monkeys performed at levels significantly better than chance, but their performance exceeded chance levels only for the first and the second selections on a trial. These data indicate that capuchin monkeys performed very similarly to chimpanzees and rhesus monkeys and appeared to plan their selection sequences during the computerized task, but only to a limited degree.

  13. Effects of 14-day treatment with the schedule III anorectic phendimetrazine on choice between cocaine and food in rhesus monkeys.

    PubMed

    Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

    2013-08-01

    The clinical utility of monoamine releasers such as phenmetrazine or d-amphetamine as candidate agonist medications for cocaine dependence is hindered by their high abuse liability. Phendimetrazine is a clinically available schedule III anorectic that functions as a prodrug for phenmetrazine and thus may have lower abuse liability. This study determined the effects of continuous 14-day treatment with phendimetrazine on cocaine vs. food choice in rhesus monkeys (N=4). Responding was maintained under a concurrent schedule of food delivery (1-g pellets, fixed-ratio 100 schedule) and cocaine injections (0-0.1mg/kg/injection, fixed-ratio 10 schedule). Cocaine choice dose-effect curves were determined daily before and during 14-day periods of continuous intravenous treatment with saline or (+)-phendimetrazine (0.32-1.0mg/kg/h). Effects of 14-day treatment with (+)-phenmetrazine (0.1-0.32 mg/kg/h; N=5) and d-amphetamine (0.032-0.1mg/kg/h; N=6) were also examined for comparison. During saline treatment, food was primarily chosen during availability of low cocaine doses (0, 0.0032, and 0.01 mg/kg/injection), and cocaine was primarily chosen during availability of higher cocaine doses (0.032 and 0.1mg/kg/injection). Phendimetrazine initially decreased overall responding without significantly altering cocaine choice. Over the course of 14 days, tolerance developed to rate decreasing effects, and phendimetrazine dose-dependently decreased cocaine choice (significant at 0.032 mg/kg/injection cocaine). Phenmetrazine and d-amphetamine produced qualitatively similar effects. These results demonstrate that phendimetrazine can produce significant, though modest, reductions in cocaine choice in rhesus monkeys. Phendimetrazine may be especially suitable as a candidate medication for human studies because of its schedule III clinical availability. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. The Effects of the Relative Strength of Simultaneous Competing Defocus Signals on Emmetropization in Infant Rhesus Monkeys

    PubMed Central

    Arumugam, Baskar; Hung, Li-Fang; To, Chi-Ho; Sankaridurg, Padmaja; III, Earl L. Smith

    2016-01-01

    Purpose We investigated how the relative surface area devoted to the more positive-powered component in dual-focus lenses influences emmetropization in rhesus monkeys. Methods From 3 to 21 weeks of age, macaques were reared with binocular dual-focus spectacles. The treatment lenses had central 2-mm zones of zero-power and concentric annular zones that had alternating powers of either +3.0 diopters (D) and 0 D (+3 D/pL) or −3.0 D and 0 D (−3 D/pL). The relative widths of the powered and plano zones varied from 50:50 to 18:82 between treatment groups. Refractive status, corneal curvature, and axial dimensions were assessed biweekly throughout the lens-rearing period. Comparison data were obtained from monkeys reared with binocular full-field single-vision lenses (FF+3D, n = 6; FF−3D, n = 10) and from 35 normal controls. Results The median refractive errors for all of the +3 D/pL lens groups were similar to that for the FF+3D group (+4.63 D versus +4.31 D to +5.25 D; P = 0.18–0.96), but significantly more hyperopic than that for controls (+2.44 D; P = 0.0002–0.003). In the −3 D/pL monkeys, refractive development was dominated by the zero-powered portions of the treatment lenses; the −3 D/pL animals (+2.94 D to +3.13 D) were more hyperopic than the FF−3D monkeys (−0.78 D; P = 0.004–0.006), but similar to controls (+2.44 D; P = 0.14–0.22). Conclusions The results demonstrate that even when the more positive-powered zones make up only one-fifth of a dual-focus lens' surface area, refractive development is still dominated by relative myopic defocus. Overall, the results emphasize that myopic defocus distributed across the visual field evokes strong signals to slow eye growth in primates. PMID:27479812

  15. Recombinant modified vaccinia virus Ankara–simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer

    PubMed Central

    Seth, Aruna; Ourmanov, Ilnour; Kuroda, Marcelo J.; Schmitz, Jörn E.; Carroll, Miles W.; Wyatt, Linda S.; Moss, Bernard; Forman, Meryl A.; Hirsch, Vanessa M.; Letvin, Norman L.

    1998-01-01

    The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans. PMID:9707609

  16. Metabolism of 14C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta).

    PubMed

    Slikker, W; Holder, C L; Lipe, G W; Korfmacher, W A; Thompson, H C; Bailey, J R

    1986-01-01

    The time-course of the metabolic fate of [14C]doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus [14C]doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-[1-phenyl-1-(2-pyridinyl)ethoxy] acetic acid, 1-[1-phenyl-1(2-pyridinyl)ethoxy] methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peak 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination.

  17. Role of basal stress hormones and amygdala dimensions in stress coping strategies of male rhesus monkeys in response to a hazard-reward conflict.

    PubMed

    Tekieh, Elaheh; Riahi, Esmail; Kazemi, Masoomeh; Sahraei, Hedayat; Tavakoli, Hassan; Aliyary, Hamed; Hajinasrollah, Mostafa; Salehi, Maryam; Meftahi, Gholamhossein; Saberi, Mehdi

    2017-08-01

    In the present study the effect of stress on monkeys that had learned to retrieve food from a five-chamber receptacle, as well as the relationship between their behavior and the serum cortisol and epinephrine levels and relative size of the amygdala was evaluated. Six male rhesus monkeys were individually given access to the food reward orderly. They could easily retrieve the rewards from all chambers except for the chamber 4, which a brief, mild electric shock (3 V) was delivered to them upon touching the chamber's interior. The coping behaviors were video-recorded and analyzed offline. Baseline serum cortisol and epinephrine levels were measured before the experiments using monkey enzyme-linked immunosorbent assay kit. One week after the behavioral experiment, the monkeys' brains were scanned using magnetic resonance imaging under general anesthesia. The cross-sectional area of the left amygdala in sagittal plane relative to the area of the whole brain in the same slice was evaluated by the planimetric method using ImageJ software. Exposure to the distressing condition caused different behavioral responses. Monkeys with higher baseline levels of serum cortisol and epinephrine and larger amygdala behaved more violently in the face of stress, indicating adopting emotion-focused stress-coping strategies. Conversely, those with low plasma epinephrine, moderate cortisol, and smaller amygdala showed perseverative behavior, indicating a problem-focused coping style. In dealing with the same stress, different responses might be observed from nonhuman primates according to their cortisol and epinephrine levels as well as their amygdala dimensions.

  18. Re-engineering primary epithelial cells from rhesus monkey parotid glands for use in developing an artificial salivary gland.

    PubMed

    Tran, Simon D; Sugito, Takayuki; Dipasquale, Giovanni; Cotrim, Ana P; Bandyopadhyay, Bidhan C; Riddle, Kathryn; Mooney, David; Kok, Marc R; Chiorini, John A; Baum, Bruce J

    2006-10-01

    There is no satisfactory conventional treatment for patients who experience irreversible salivary gland damage after therapeutic radiation for head and neck cancer or because of Sjögren's syndrome. Additionally, if most parenchyma is lost, these patients also are not candidates for evolving gene transfer strategies. To help such patients, several years ago we began to develop an artificial salivary gland. In the present study, we used a non-human primate tissue source, parotid glands from rhesus monkeys, to obtain potential autologous graft cells for development of a prototype device for in situ testing. Herein, we present 3 major findings. First, we show that primary cultures of rhesus parotid gland (RPG) cells are capable of attaining a polarized orientation, with Na(+)/K(+)-adenosine triphosphatase, zonula occludens-1, and claudin-1 distributed in specific domains appropriate for epithelial cells. Second, we show that RPG cells exhibit 2 essential epithelial functions required for graft cells in an artificial salivary gland device (i.e., an effective barrier to paracellular water flow and the generation of a moderate transepithelial electrical resistance). Third, we show that RPG cells can express functional water channels, capable of mediating directional fluid movement, after transduction by adenoviral and adeno-associated virus type 2 vectors. Together these results demonstrate that it is feasible to individually prepare RPG cells for eventual use in a prototype artificial salivary gland.

  19. Specific α4β2 Nicotinic Acetylcholine Receptor Binding of [F-18]Nifene in the Rhesus Monkey

    PubMed Central

    Hillmer, A.T.; Wooten, D.W.; Moirano, J.; Slesarev, M.; Barnhart, T.E.; Engle, J.W.; Nickles, R.J.; Murali, D.; Schneider, M.; Mukherjee, J.; Christian, B.T.

    2013-01-01

    Objective [F-18]Nifene is a PET radioligand developed to image α4β2* nicotinic acetylcholine receptors (nAChR) in the brain. This work assesses the in vivo binding and imaging characteristics of [F-18]nifene in rhesus monkeys for the development of PET experiments examining nAChR binding. Methods Dynamic PET imaging experiments with [F-18]nifene were acquired in 4 anesthetized macaca mulatta (rhesus) monkeys using a microPET P4 scanner. Data acquisition was initiated with a bolus injection of 109 ± 17 MBq [F-18]nifene and the time course of the radioligand in the brain was measured for up to 120 minutes. For two experiments, a displacement dose of (−)nicotine (0.03 mg/kg, i.v.) was given 45–60 minutes post injection and followed 30 minutes later with a second [F-18]nifene injection to measure radioligand nondisplaceable uptake. Time activity curves were extracted in the regions of the antereoventral thalamus (AVT), lateral geniculate nucleus region (LGN), frontal cortex, and the cerebellum (CB). Results The highest levels of [F-18]nifene uptake were observed in the AVT and LGN. Target-to-CB ratios reached maximum values of 3.3 ± 0.4 in the AVT and 3.2 ± 0.3 in the LG 30–45 minutes post-injection. Significant binding of [F-18]nifene was observed in the subiculum, insula cortex, temporal cortex, cingulate gyrus, frontal cortex, striatum, and midbrain areas. The (−)nicotine displaced bound [F-18]nifene to near background levels within 15 minutes post-drug injection. No discernable displacement was observed in the CB, suggesting its potential as a reference region. Logan graphical estimates using the CB as a reference region yielded binding potentials (BPND) of 1.6 ± 0.1 in the AVT, and 1.3 ± 0.1 in the LGN. The post-nicotine injection displayed uniform nondisplaceable uptake of [F-18]nifene throughout gray and white brain matter. Conclusions [F-18]Nifene exhibits rapid equilibration and a moderately high target to background binding profile in the α4

  20. Repeated Administration of a Mutant Cocaine Esterase: Effects on Plasma Cocaine Levels, Cocaine-Induced Cardiovascular Activity, and Immune Responses in Rhesus Monkeys

    PubMed Central

    Collins, Gregory T.; Brim, Remy L.; Noon, Kathleen R.; Narasimhan, Diwahar; Lukacs, Nicholas W.; Sunahara, Roger K.; Woods, James H.

    2012-01-01

    Previous studies have demonstrated the capacity of a long-acting mutant form of a naturally occurring bacterial double mutant cocaine esterase (DM CocE) to antagonize the reinforcing, discriminative, convulsant, and lethal effects of cocaine in rodents and reverse the increases in mean arterial pressure (MAP) and heart rate (HR) produced by cocaine in rhesus monkeys. This study was aimed at characterizing the immunologic responses to repeated dosing with DM CocE and determining whether the development of anti-CocE antibodies altered the capacity of DM CocE to reduce plasma cocaine levels and ameliorate the cardiovascular effects of cocaine in rhesus monkeys. Under control conditions, intravenous administration of cocaine (3 mg/kg) resulted in a rapid increase in the plasma concentration of cocaine (n = 2) and long-lasting increases in MAP and HR (n = 3). Administration of DM CocE (0.32 mg/kg i.v.) 10 min after cocaine resulted in a rapid hydrolysis of cocaine with plasma levels below detection limits within 5 to 8 min. Elevations in MAP and HR were significantly reduced within 25 and 50 min of DM CocE administration, respectively. Although slight (10-fold) increases in anti-CocE antibodies were observed after the fourth administration of DM CocE, these antibodies did not alter the capacity of DM CocE to reduce plasma cocaine levels or ameliorate cocaine's cardiovascular effects. Anti-CocE titers were transient and generally dissipated within 8 weeks. Together, these results suggest that highly efficient cocaine esterases, such as DM CocE, may provide a novel and effective therapeutic for the treatment of acute cocaine intoxication in humans. PMID:22518021

  1. Associations between Parity, Hair Hormone Profiles during Pregnancy and Lactation, and Infant Development in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Dettmer, Amanda M.; Rosenberg, Kendra L.; Suomi, Stephen J.; Meyer, Jerrold S.; Novak, Melinda A.

    2015-01-01

    Studies examining hormones throughout pregnancy and lactation in women have been limited to single, or a few repeated, short-term measures of endocrine activity. Furthermore, potential differences in chronic hormonal changes across pregnancy/lactation between first-time and experienced mothers are not well understood, especially as they relate to infant development. Hormone concentrations in hair provide long-term assessments of hormone production, and studying these measures in non-human primates allows for repeated sampling under controlled conditions that are difficult to achieve in humans. We studied hormonal profiles in the hair of 26 female rhesus monkeys (Macaca mulatta, n=12 primiparous), to determine the influences of parity on chronic levels of cortisol (hair cortisol concentration, HCC) and progesterone (hair progesterone concentration, HPC) during early- to mid-pregnancy (PREG1), in late pregnancy/early lactation (PREG2/LACT1), and in peak lactation (LACT2). We also assessed infants’ neurobehavioral development across the first month of life. After controlling for age and stage of pregnancy at the first hair sampling period, we found that HCCs overall peaked in PREG2/LACT1 (p=0.02), but only in primiparous monkeys (p<0.001). HPCs declined across pregnancy and lactation for all monkeys (p<0.01), and primiparous monkeys had higher HPCs overall than multiparous monkeys (p=0.02). Infants of primiparous mothers had lower sensorimotor reflex scores (p=0.02) and tended to be more irritable (p=0.05) and less consolable (p=0.08) in the first month of life. Moreover, across all subjects, HCCs in PREG2/LACT1 were positively correlated with irritability (r(s)=0.43, p=0.03) and negatively correlated with sensorimotor scores (r(s)=-0.41, p=0.04). Together, the present results indicate that primiparity influences both chronic maternal hormonal profiles and infant development. These effects may, in part, reflect differential reproductive and maternal effort in

  2. Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta).

    PubMed

    Dow, Geoffrey S; Gettayacamin, Montip; Hansukjariya, Pranee; Imerbsin, Rawiwan; Komcharoen, Srawuth; Sattabongkot, Jetsumon; Kyle, Dennis; Milhous, Wilbur; Cozens, Simon; Kenworthy, David; Miller, Anne; Veazey, Jim; Ohrt, Colin

    2011-07-29

    Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns. In 2005, the radical curative efficacy of tafenoquine combinations was investigated in Plasmodium cynomolgi-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD). In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans. The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg versus 18 mg/kg) than for monotherapy. This regimen (1.8 mg/kg) was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg) was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg) appears to be biologically equivalent to a 600-1200 mg dose in humans. At

  3. Radical curative efficacy of tafenoquine combination regimens in Plasmodium cynomolgi-infected Rhesus monkeys (Macaca mulatta)

    PubMed Central

    2011-01-01

    Background Tafenoquine is an 8-aminoquinoline being developed for radical cure (blood and liver stage elimination) of Plasmodium vivax. During monotherapy treatment, the compound exhibits slow parasite and fever clearance times, and toxicity in glucose-6-phosphate dehydrogenase (G6PD) deficiency is a concern. Combination with other antimalarials may mitigate these concerns. Methods In 2005, the radical curative efficacy of tafenoquine combinations was investigated in Plasmodium cynomolgi-infected naïve Indian-origin Rhesus monkeys. In the first cohort, groups of two monkeys were treated with a three-day regimen of tafenoquine at different doses alone and in combination with a three-day chloroquine regimen to determine the minimum curative dose (MCD). In the second cohort, the radical curative efficacy of a single-day regimen of tafenoquine-mefloquine was compared to that of two three-day regimens comprising tafenoquine at its MCD with chloroquine or artemether-lumefantrine in groups of six monkeys. In a final cohort, the efficacy of the MCD of tafenoquine against hypnozoites alone and in combination with chloroquine was investigated in groups of six monkeys after quinine pre-treatment to eliminate asexual parasites. Plasma tafenoquine, chloroquine and desethylchloroquine concentrations were determined by LC-MS in order to compare doses of the drugs to those used clinically in humans. Results The total MCD of tafenoquine required in combination regimens for radical cure was ten-fold lower (1.8 mg/kg versus 18 mg/kg) than for monotherapy. This regimen (1.8 mg/kg) was equally efficacious as monotherapy or in combination with chloroquine after quinine pre-treatment to eliminate asexual stages. The same dose of (1.8 mg/kg) was radically curative in combination with artemether-lumefantrine. Tafenoquine was also radically curative when combined with mefloquine. The MCD of tafenoquine monotherapy for radical cure (18 mg/kg) appears to be biologically equivalent to a 600

  4. Spacelab flight simulated by two monkeys at CERMA

    NASA Technical Reports Server (NTRS)

    Langereux, P.

    1980-01-01

    A semiautomatic module for two monkeys was designed. The module shelters two Rhesus monkeys seated side by side in a compartment, reducing the emotional stresses caused by isolation. Food pellets, water, and air are supplied and body wastes are automatically removed. Physiological and environmental parameters are continually monitored, making possible the performance of experiments concerning the pathophysiological mechanisms of the disorders of weightlessness. A ten day flight of the module in Spacelab was simulated.

  5. Rhesus macaques recognize unique multi-modal face-voice relations of familiar individuals and not of unfamiliar ones

    PubMed Central

    Habbershon, Holly M.; Ahmed, Sarah Z.; Cohen, Yale E.

    2013-01-01

    Communication signals in non-human primates are inherently multi-modal. However, for laboratory-housed monkeys, there is relatively little evidence in support of the use of multi-modal communication signals in individual recognition. Here, we used a preferential-looking paradigm to test whether laboratory-housed rhesus could “spontaneously” (i.e., in the absence of operant training) use multi-modal communication stimuli to discriminate between known conspecifics. The multi-modal stimulus was a silent movie of two monkeys vocalizing and an audio file of the vocalization from one of the monkeys in the movie. We found that the gaze patterns of those monkeys that knew the individuals in the movie were reliably biased toward the individual that did not produce the vocalization. In contrast, there was not a systematic gaze pattern for those monkeys that did not know the individuals in the movie. These data are consistent with the hypothesis that laboratory-housed rhesus can recognize and distinguish between conspecifics based on auditory and visual communication signals. PMID:23774779

  6. Can Monkeys (Macaca mulatta) Represent Invisible Displacement?

    NASA Technical Reports Server (NTRS)

    Filion, Christine M.; Washburn, David A.; Gulledge, Jonathan P.

    1996-01-01

    Four experiments were conducted to assess whether or not rhesus macaques (Macaca mulatta) could represent the unperceived movements of a stimulus. Subjects were tested on 2 computerized tasks, HOLE (monkeys) and LASER (humans and monkeys), in which subjects needed to chase or shoot at, respectively, a moving target that either remained visible or became invisible for a portion of its path of movement. Response patterns were analyzed and compared between target-visible and target-invisible conditions. Results of Experiments 1, 2, and 3 demonstrated that the monkeys are capable of extrapolating movement. That this extrapolation involved internal representation of the target's invisible movement was suggested but not confirmed. Experiment 4, however, demonstrated that the monkeys are capable of representing the invisible displacements of a stimulus.

  7. Sex and menstrual cycle effects on chronic oral cocaine self-administration in rhesus monkeys: Effects of a nondrug alternative reward.

    PubMed

    Carroll, Marilyn E; Collins, Molly; Kohl, Emily A; Johnson, Seth; Dougen, Ben

    2016-08-01

    In previous studies, female monkeys self-administered more oral phencyclidine (PCP) than males, and PCP intake differed by phase of menstrual cycle. The purpose of this study was to examine sex and hormonal influences on oral cocaine self-administration in male and female rhesus monkeys in the follicular vs. luteal phases of the menstrual cycle, with concurrent access to an alternative nondrug reward, saccharin (SACC) vs. water. Concurrent access to cocaine (0.2, 0.4, and 0.8 mg/ml) and SACC or water was available from two drinking spouts under concurrent fixed-ratio (FR) 2, 4, and 8 schedules during daily 3-h sessions. Cocaine deliveries were similar in males and females in the females' luteal phase, but cocaine deliveries were higher in females during the follicular phase than the luteal phase and compared to males. When SACC was available, cocaine deliveries were reduced in females in the follicular phase of the cycle, and cocaine intake (mg/kg) was reduced in males and in females' follicular and luteal phases. Access to concurrent SACC (vs. water) reduced cocaine intake (mg/kg) in males and in females during both menstrual phases, and the magnitude of the reduction in cocaine intake was greatest during the females' follicular phase. Thus, a nondrug alternative reward, SACC, is a viable alternative treatment for reducing cocaine's rewarding effects on male and female monkeys, and reductions in cocaine seeking were optimal in the females' luteal phase.

  8. Adaptation of skeletal muscle to spaceflight: Cosmos rhesus project. Cosmos 2044 and 2229

    NASA Technical Reports Server (NTRS)

    Bodine-Fowler, Sue

    1994-01-01

    The proposed experiments were designed to determine the effects of the absence of weight support on hindlimb muscles of the monkey: an ankle flexor (tibialis anterior, TA), two ankle extensors (medial gastrocnemius, MG and soleus, SOL), and a knee extensor (vastus lateralis, VL). These effects were assessed by examining the biochemical and morphological properties of muscle fibers obtained from biopsies in young Rhesus monkeys (3-4 Kg). Biopsies taken from ground base experiments were analyzed to determine: (1) the effects of chair restraint at 1 G on muscle properties and (2) the growth rate of flexor and extensor muscles in the Rhesus. In addition, two sets of biopsies were taken from monkeys which were in the flight pool and the four monkeys that flew on the Cosmos 2044 and 2229 biosatellite missions. Based on data collected in rats it is generally assumed that extensors atrophy to a greater extent than flexors in response to spaceflight or hindlimb suspension. Consequently, the finding that fibers in the TA (a fast flexor) of the flight monkeys atrophied, whereas fibers in the Sol (a predominantly slow extensor) and MG (a fast extensor) grew after a 14-day spaceflight (Cosmos 2044) and 12-day spaceflight (Cosmos 2229) was unexpected. In Cosmos 2044, the TA in both flight monkeys had a 21 percent decrease in fiber size, whereas the Sol and MG both had a 79 percent increase in fiber size. In Cosmos 2229, the TA in both flight monkeys showed significant atrophy, whereas the Sol and MG showed slight growth in one monkey (906) and slight atrophy in the other monkey (151).

  9. A geometric analysis of semicircular canals and induced activity in their peripheral afferents in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Reisine, H.; Simpson, J. I.; Henn, V.

    1988-01-01

    Experiments were carried out to determine anatomically the planes of the semicircular canals of two juvenile rhesus monkeys, using plastic casts of the semicircular canals, and the anatomical measurements were related to the directional coding of neural signals transmitted by primary afferents innervating the same simicircular canals. In the experiments, animals were prepared for monitoring the eye position by the implantation of silver-silver chloride electrodes into the bony orbit. Following the recording of semicircular canal afferent activity, the animals were sacrificed; plastic casting resin was injected into the bony canals; and, when the temporal bone was demineralized and removed, the coordinates of points spaced along the circumference of the canal casts were measured. A comparison of the sensitivity vectors determined in these experiments and the anatomical measures showed that the average difference between a sensitivity vector and its respective normal vector was 6.3 deg.

  10. Assessment of the clinical cardiac drug-drug interaction associated with the combination of hepatitis C virus nucleotide inhibitors and amiodarone in guinea pigs and rhesus monkeys.

    PubMed

    Regan, Christopher P; Morissette, Pierre; Regan, Hillary K; Travis, Jeffery J; Gerenser, Pamela; Wen, Jianzhong; Fitzgerald, Kevin; Gruver, Shaun; DeGeorge, Joseph J; Sannajust, Frederick J

    2016-11-01

    In 2015, European and U.S. health agencies issued warning letters in response to 9 reported clinical cases of severe bradycardia/bradyarrhythmia in hepatitis C virus (HCV)-infected patients treated with sofosbuvir (SOF) in combination with other direct acting antivirals (DAAs) and the antiarrhythmic drug, amiodarone (AMIO). We utilized preclinical in vivo models to better understand this cardiac effect, the potential pharmacological mechanism(s), and to identify a clinically translatable model to assess the drug-drug interaction (DDI) cardiac risk of current and future HCV inhibitors. An anesthetized guinea pig model was used to elicit a SOF+AMIO-dependent bradycardia. Detailed cardiac electrophysiological studies in this species revealed SOF+AMIO-dependent selective nodal dysfunction, with initial, larger effects on the sinoatrial node. Further studies in conscious, rhesus monkeys revealed an emergent bradycardia and bradyarrhythmia in 3 of 4 monkeys administered SOF+AMIO, effects not observed with either agent alone. Morever, bradycardia and bradyarrhythmia were not observed in rhesus monkeys when intravenous infusion of MK-3682 was completed after AMIO pretreatment. These are the first preclinical in vivo experiments reported to replicate the severe clinical SOF+AMIO cardiac DDI and provide potential in vivo mechanism of action. As such, these data provide a preclinical risk assessment paradigm, including a clinically relevant nonhuman primate model, with which to better understand cardiovascular DDI risk for this therapeutic class. Furthermore, these studies suggest that not all HCV DAAs and, in particular, not all HCV nonstructural protein 5B inhibitors may exhibit this cardiac DDI with amiodarone. Given the selective in vivo cardiac electrophysiological effect, these data enable targeted cellular/molecular mechanistic studies to more precisely identify cell types, receptors, and/or ion channels responsible for the clinical DDI. (Hepatology 2016

  11. Aptamer Against Mannose-capped Lipoarabinomannan Inhibits Virulent Mycobacterium tuberculosis Infection in Mice and Rhesus Monkeys

    PubMed Central

    Pan, Qin; Wang, Qilong; Sun, Xiaoming; Xia, Xianru; Wu, Shimin; Luo, Fengling; Zhang, Xiao-Lian

    2014-01-01

    The major surface lipoglycan of Mycobacterium tuberculosis (M. tb), mannose-capped lipoarabinomannan (ManLAM), is an immunosuppressive epitope of M. tb. We used systematic evolution of ligands by exponential enrichment (SELEX) to generate an aptamer (ZXL1) that specifically bound to ManLAM from the virulent M. tb strain H37Rv. Aptamer ZXL1 had the highest binding affinity, with an equilibrium dissociation constant (Kd) of 436.3 ± 37.84 nmol/l, and competed with the mannose receptor for binding to ManLAM and M. tb H37Rv. ZXL1 significantly inhibited the ManLAM-induced immunosuppression of CD11c+ dendritic cells (DCs) and enhanced the M. tb antigen–presenting activity of DCs for naive CD4+ Th1 cell activation. More importantly, we demonstrated that injection of aptamer ZXL1 significantly reduced the progression of M. tb H37Rv infections and bacterial loads in lungs of mice and rhesus monkeys. These results suggest that the aptamer ZXL1 is a new potential antimycobacterial agent and tuberculosis vaccine immune adjuvant. PMID:24572295

  12. Effects of amphetamine, morphine, and CP 55, 940 on Go/No-Go task performance in rhesus monkeys.

    PubMed

    Koek, Wouter; Gerak, Lisa R; France, Charles P

    2015-08-01

    In humans, impulsivity measured as false alarms in a Go/No-Go task is reportedly decreased by amphetamine and is not affected by oxycodone and delta(9)-tetrahydrocannabinol. To model these findings in animals, three rhesus monkeys were trained to perform a food-reinforced Go/No-Go task. In this task, amphetamine was found to decrease false alarms (i.e. responding during No-Go trials), but only at doses that also decreased hits (i.e. responding during Go trials). Morphine generally decreased hits but not false alarms. The cannabinoid receptor agonist CP 55, 940 decreased both false alarms and hits, but only at doses that also decreased the number of trials completed. Additional studies in animals and humans are necessary to delineate the conditions under which amphetamine and other psychoactive drugs affect impulsivity in Go/No-Go tasks.

  13. A non-invasive method for studying an index of pupil diameter and visual performance in the rhesus monkey.

    PubMed

    Fairhall, Sarah J; Dickson, Carol A; Scott, Leah; Pearce, Peter C

    2006-04-01

    A non-invasive model has been developed to estimate gaze direction and relative pupil diameter, in minimally restrained rhesus monkeys, to investigate the effects of low doses of ocularly administered cholinergic compounds on visual performance. Animals were trained to co-operate with a novel device, which enabled eye movements to be recorded using modified human eye-tracking equipment, and to perform a task which determined visual threshold contrast. Responses were made by gaze transfer under twilight conditions. 4% w/v pilocarpine nitrate was studied to demonstrate the suitability of the model. Pilocarpine induced marked miosis for >3 h which was accompanied by a decrement in task performance. The method obviates the need for invasive surgery and, as the position of point of gaze can be approximately defined, the approach may have utility in other areas of research involving non-human primates.

  14. The misbehaviour of a metacognitive monkey

    PubMed Central

    Sayers, Ken; Evans, Theodore A.; Menzel, Emilie; Smith, J. David; Beran, Michael J.

    2015-01-01

    Summary Metacognition, the monitoring of one’s own mental states, is a fundamental aspect of human intellect. Despite tests in nonhuman animals suggestive of uncertainty monitoring, some authors interpret these results solely in terms of primitive psychological mechanisms and reinforcement regimes, where “reinforcement” is invariably considered to be the delivery and consumption of earned food rewards. Surprisingly, few studies have detailed the trial-by-trial behaviour of animals engaged in such tasks. Here we report ethology-based observations on a rhesus monkey completing sparse-dense discrimination problems, and given the option of escaping trials (i.e., responding “uncertain”) at its own choosing. Uncertainty responses were generally made on trials of high objective difficulty, and were characterized by long latencies before beginning visible trials, long times taken for response, and, even after controlling for difficulty, high degrees of wavering during response. Incorrect responses were also common in trials of high objective difficulty, but were characterized by low degrees of wavering. This speaks to the likely adaptive nature of “hesitation,” and is inconsistent with models which argue or predict implicit, inflexible information-seeking or “alternative option” behaviours whenever challenging problems present themselves, Confounding models which suggest that nonhuman behaviour in metacognition tasks is driven solely by food delivery/consumption, the monkey was also observed allowing pellets to accumulate and consuming them during and after trials of all response/outcome categories (i.e., whether correct, incorrect, or escaped). This study thus bolsters previous findings that rhesus monkey behaviour in metacognition tasks is in some respects disassociated from mere food delivery/consumption, or even the avoidance of punishment. These and other observations fit well with the evolutionary status and natural proclivities of rhesus monkeys

  15. Behavioral Determinants of Cannabinoid Self-Administration in Old World Monkeys.

    PubMed

    John, William S; Martin, Thomas J; Nader, Michael A

    2017-06-01

    Reinforcing effects of Δ 9 -tetrahydrocannabinol (THC), the primary active ingredient in marijuana, as assessed with self-administration (SA), has only been established in New World primates (squirrel monkeys). The objective of this study was to investigate some experimental factors that may enhance intravenous SA of THC and the cannabinoid receptor (CBR) agonist CP 55 940 in Old World monkeys (rhesus and cynomolgus), a species that has been used extensively in biomedical research. In one experiment, male rhesus monkeys (N=9) were trained to respond under a fixed-ratio 10 schedule of food presentation. The effects of CP 55 940 (1.0-10 μg/kg, i.v.) and THC (3.0-300 μg/kg, i.v.) on food-maintained responding and body temperature were determined in these subjects prior to giving them access to self-administer each drug. Both drugs dose-dependently decreased food-maintained responding. CP 55 940 (0.001-3.0 μg/kg) functioned as a reinforcer in three monkeys, whereas THC (0.01-10 μg/kg) did not have reinforcing effects in any subject. CP 55 940 was least potent to decrease food-maintained responding in the monkeys in which CP 55 940 functioned as a reinforcer. Next, THC was administered daily to monkeys until tolerance developed to rate-decreasing effects. When THC SA was reexamined, it functioned as a reinforcer in three monkeys. In a group of cocaine-experienced male cynomolgus monkeys (N=4), THC SA was examined under a second-order schedule of reinforcement; THC functioned as reinforcer in two monkeys. These data suggest that SA of CBR agonists may be relatively independent of their rate-decreasing effects in Old World monkeys. Understanding individual differences in vulnerability to THC SA may lead to novel treatment strategies for marijuana abuse.

  16. Metabolism of /sup 14/C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta)

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Slikker, W. Jr.; Holder, C.L.; Lipe, G.W.

    The time-course of the metabolic fate of (/sup 14/C)doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus (/sup 14/C)doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-(1-phenyl-1-(2-pyridinyl)ethoxy) acetic acid, 1-(1-phenyl-1(2-pyridinyl)ethoxy) methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peakmore » 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination.« less

  17. Change Detection by Rhesus Monkeys (Macaca mulatta) and Pigeons (Columba livia)

    PubMed Central

    Elmore, L. Caitlin; Magnotti, John F.; Katz, Jeffrey S.; Wright, Anthony A.

    2012-01-01

    Two monkeys learned a color change-detection task where two colored circles (selected from a 4-color set) were presented on a 4×4 invisible matrix. Following a delay, the correct response was to touch the changed colored circle. The monkeys' learning, color transfer, and delay transfer were compared to a similar experiment with pigeons. Monkeys, like pigeons, showed full transfer to four novel colors, and to delays as long as 6.4 s, suggesting they remembered the colors as opposed to perceptual based attentional capture process that may work at very short delays. The monkeys and pigeons were further tested to compare transfer to other dimensions. Monkeys transferred to shape and location changes, unlike the pigeons, but neither species transferred to size changes. Thus, monkeys were less restricted in their domain to detect change than pigeons, but both species learned the basic task and appear suitable for comparative studies of visual short-term memory. PMID:22428982

  18. Effect of spaceflight on the isotonic contractile properties of single skeletal muscle fibers in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Romatowski, J. G.; Blaser, C.; De La Cruz, L.; Gettelman, G. J.; Widrick, J. J.

    2000-01-01

    Experiments from both Cosmos and Space Shuttle missions have shown weightlessness to result in a rapid decline in the mass and force of rat hindlimb extensor muscles. Additionally, despite an increased maximal shortening velocity, peak power was reduced in rat soleus muscle post-flight. In humans, declines in voluntary peak isometric ankle extensor torque ranging from 15-40% have been reported following long- and short-term spaceflight and prolonged bed rest. Complete understanding of the cellular events responsible for the fiber atrophy and the decline in force, as well as the development of effective countermeasures, will require detailed knowledge of how the physiological and biochemical processes of muscle function are altered by spaceflight. The specific purpose of this investigation was to determine the extent to which the isotonic contractile properties of the slow- and fast-twitch fiber types of the soleus and gastrocnemius muscles of rhesus monkeys (Macaca mulatta) were altered by a 14-day spaceflight.

  19. Characterization and storage of malaria antigens: Fractionation of Plasmodium knowlesi-induced antigens of rhesus monkey erythrocyte membranes*

    PubMed Central

    Schmidt-Ullrich, R.; Wallach, D. F. H.; Lightholder, J.

    1979-01-01

    In order to characterize parasite-induced host cell membrane antigens, the plasma membranes of Plasmodium knowlesi-infected rhesus erythrocytes have been compared with those of normal red cells and purified schizonts by immunochemical and biochemical techniques. Host cell membranes and schizonts were separated by differential centrifugation following nitrogen decompression. Isolated schizonts were further fractionated into several subcellular compartments. Crossed-immune electrophoresis, against monkey anti-schizont serum, of Triton X-100-solubilized material identified 7 P. knowlesi-specific antigens, of which 4 could be detected only in the host cell membranes. These membranes also contained 3 proteins, with relative molecular masses of 55 000, 65 000 and 90 000 and isoelectric points at pH 4.5, 4.5 and 5.2, respectively, which are lacking in normal membranes. Pulse-chase experiments with (14C)-glucosamine showed that these parasite-induced host cell membrane components are glycoproteins. ImagesFig. 1Fig. 2 PMID:120762

  20. Effects of Vector Backbone and Pseudotype on Lentiviral Vector-mediated Gene Transfer: Studies in Infant ADA-Deficient Mice and Rhesus Monkeys

    PubMed Central

    Carbonaro Sarracino, Denise; Tarantal, Alice F; Lee, C Chang I.; Martinez, Michele; Jin, Xiangyang; Wang, Xiaoyan; Hardee, Cinnamon L; Geiger, Sabine; Kahl, Christoph A; Kohn, Donald B

    2014-01-01

    Systemic delivery of a lentiviral vector carrying a therapeutic gene represents a new treatment for monogenic disease. Previously, we have shown that transfer of the adenosine deaminase (ADA) cDNA in vivo rescues the lethal phenotype and reconstitutes immune function in ADA-deficient mice. In order to translate this approach to ADA-deficient severe combined immune deficiency patients, neonatal ADA-deficient mice and newborn rhesus monkeys were treated with species-matched and mismatched vectors and pseudotypes. We compared gene delivery by the HIV-1-based vector to murine γ-retroviral vectors pseudotyped with vesicular stomatitis virus-glycoprotein or murine retroviral envelopes in ADA-deficient mice. The vesicular stomatitis virus-glycoprotein pseudotyped lentiviral vectors had the highest titer and resulted in the highest vector copy number in multiple tissues, particularly liver and lung. In monkeys, HIV-1 or simian immunodeficiency virus vectors resulted in similar biodistribution in most tissues including bone marrow, spleen, liver, and lung. Simian immunodeficiency virus pseudotyped with the gibbon ape leukemia virus envelope produced 10- to 30-fold lower titers than the vesicular stomatitis virus-glycoprotein pseudotype, but had a similar tissue biodistribution and similar copy number in blood cells. The relative copy numbers achieved in mice and monkeys were similar when adjusted to the administered dose per kg. These results suggest that this approach can be scaled-up to clinical levels for treatment of ADA-deficient severe combined immune deficiency subjects with suboptimal hematopoietic stem cell transplantation options. PMID:24925206

  1. Effects of vector backbone and pseudotype on lentiviral vector-mediated gene transfer: studies in infant ADA-deficient mice and rhesus monkeys.

    PubMed

    Carbonaro Sarracino, Denise; Tarantal, Alice F; Lee, C Chang I; Martinez, Michele; Jin, Xiangyang; Wang, Xiaoyan; Hardee, Cinnamon L; Geiger, Sabine; Kahl, Christoph A; Kohn, Donald B

    2014-10-01

    Systemic delivery of a lentiviral vector carrying a therapeutic gene represents a new treatment for monogenic disease. Previously, we have shown that transfer of the adenosine deaminase (ADA) cDNA in vivo rescues the lethal phenotype and reconstitutes immune function in ADA-deficient mice. In order to translate this approach to ADA-deficient severe combined immune deficiency patients, neonatal ADA-deficient mice and newborn rhesus monkeys were treated with species-matched and mismatched vectors and pseudotypes. We compared gene delivery by the HIV-1-based vector to murine γ-retroviral vectors pseudotyped with vesicular stomatitis virus-glycoprotein or murine retroviral envelopes in ADA-deficient mice. The vesicular stomatitis virus-glycoprotein pseudotyped lentiviral vectors had the highest titer and resulted in the highest vector copy number in multiple tissues, particularly liver and lung. In monkeys, HIV-1 or simian immunodeficiency virus vectors resulted in similar biodistribution in most tissues including bone marrow, spleen, liver, and lung. Simian immunodeficiency virus pseudotyped with the gibbon ape leukemia virus envelope produced 10- to 30-fold lower titers than the vesicular stomatitis virus-glycoprotein pseudotype, but had a similar tissue biodistribution and similar copy number in blood cells. The relative copy numbers achieved in mice and monkeys were similar when adjusted to the administered dose per kg. These results suggest that this approach can be scaled-up to clinical levels for treatment of ADA-deficient severe combined immune deficiency subjects with suboptimal hematopoietic stem cell transplantation options.

  2. Effects of damage to the suprachiasmatic area of the anterior hypothalamus on the daily melatonin and cortisol rhythms in the rhesus monkey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Reppert, S.M.; Perlow, M.J.; Ungerleider, L.G.

    The effects of lesions of the suprachiasmatic nucleus (SCN) on the circadian rhythms in melatonin and cortisol were examined in the rhesus monkey. The concentrations of the two hormones were monitored in cerebrospinal fluid (CSF) withdrawn from two sham-operated animals, two animals with complete bilateral SCN lesions, and two animals with partial SCN damage at 4 and 8 months after surgery. In the sham-operated animals, as in the intact animal, the daily melatonin rhythm was entrained to the daily light-dark cycle, was suppressed in constant light, and persisted in constant darkness. In contrast, neither animal with complete SCN ablation exhibitedmore » a daily pattern of CSF melatonin in diurnal lighting at 4 months after surgery nor were their melatonin levels at constant low values. Furthermore, CSF melatonin concentrations were not suppressed in either animal by constant light. Surprisingly, at 8 months after surgery, spectral analysis revealed a 24-hr component to the melatonin patterns for each animal with complete SCN ablation in both diurnal lighting and constant darkness. The two animals with partial SCN damage exhibited a daily melatonin rhythm in diurnal lighting, but constant light did not suppress CSF melatonin concentrations consistently. Daily rhythms persisted in both for a 6 1/2-d period of study in constant darkness. In contrast to the alterations in the melatonin rhythm after SCN damage, there was no apparent effect of either partial or complete SCN ablation on the daily CSF cortisol rhythm. These data indicate that, in the rhesus monkey, the SCN is important for the generation, photic entrainment, and photic suppression of the melatonin rhythm. However, circadian oscillators located outside of the SCN region may control the normal daily cortisol rhythm and perhaps the melatonin rhythm in the absence of the SCN.« less

  3. Sex and menstrual cycle effects on chronic oral cocaine self-administration in rhesus monkeys: Effects of a nondrug alternative reward

    PubMed Central

    Carroll, Marilyn E.; Collins, Molly; Kohl, Emily A.; Johnson, Seth; Dougen, Ben

    2016-01-01

    Background In previous studies female monkeys self-administered more oral phencyclidine (PCP) than males, and PCP intake differed by phase of menstrual cycle. Objectives The purpose of this study was to examine sex and hormonal influences on oral cocaine self-administration in male and female rhesus monkeys in the follicular vs. luteal phases of the menstrual cycle, with concurrent access to an alternative nondrug reward, saccharin (SACC) vs. water. Materials and methods Concurrent access to cocaine (0.2, 0.4 and 0.8 mg/ml) and SACC or water was available from two drinking spouts under concurrent fixed-ratio (FR) 2, 4, and 8 schedules during daily 3-h sessions. Results Cocaine deliveries were similar in males and females in the females’ luteal phase, but cocaine deliveries were higher in females during the follicular phase than the luteal phase and compared to males. When SACC was available cocaine deliveries were reduced in females in the follicular phase of the cycle, and cocaine intake (mg/kg) was reduced in males and in females’ follicular and luteal phases. Conclusions Access to concurrent SACC (vs. water) reduced cocaine intake (mg/kg) in males and in females during both menstrual phases, and the magnitude of the reduction in cocaine intake was greatest during the females’ follicular phase. Thus, a nondrug alternative reward, SACC, is a viable alternative treatment for reducing cocaine’s rewarding effects on male and female monkeys, and reductions in cocaine-seeking were optimal in the females’ luteal phase. PMID:27318989

  4. Light and Gravity Effects on Circadian Rhythms of Rhesus Macaques

    NASA Technical Reports Server (NTRS)

    Fuller, Charles

    1997-01-01

    Temporal integration of a biological organism's physiological, behavioral and biochemical systems depends upon its circadian timing system. The endogenous period of this timing system is typically synchronized to the 24- hour day by environmental cues. The daily alternation of light and dark has long been known as one of the most potent environmental synchronizers influencing the circadian timing system. Alterations in the lighting environment (length or intensity of light exposure) can also affect the homeostatic state of the organism. A series of experiments was performed using rhesus monkeys with the objective of defining the fundamental properties of the circadian rhythm of body temperature. Three major experiments were performed in addition to several preliminary studies. These experiments explored 1.) the response of the rhesus body temperature rhythm to varying day length and light intensity; 2.) the response of the body temperature rhythm to light exposure as a function of time of day; and 3.) the characteristics of the metabolic heat production rhythm which is responsible for the daily cycle in body temperature. Results of these three completed experiments will be reported here. In addition, preliminary experiments were also performed in social entrainment of rhesus circadian rhythms and the properties of rhesus body temperature rhythms in constant conditions, where no external time cues were provided. Four adult male rhesus monkeys served as subjects in all experiments. All experiments were performed at the California Regional Primate Research Center. Each animal was implanted with a biotelemetry unit that measured deep body temperature. All surgeries were performed by a board certified veterinary surgeon under sterile conditions. The biotelemetry implants also provided an index of activity level in each animal. For metabolic heat production measurements, oxygen consumption and carbon dioxide production were measured and the caloric equivalent of these

  5. Note on hand use in the manipulation of joysticks by rhesus monkeys (Macaca mulatta) and chimpanzees (Pan troglodytes)

    NASA Technical Reports Server (NTRS)

    Hopkins, William D.; Washburn, David A.; Rumbaugh, Duane M.

    1989-01-01

    MacNeilage et al. (1987) have proposed that nonhuman primate handedness may be contingent on the specific task requirements, with visual-spatial tasks yielding left-hand preferences and fine-motor tasks producing right-hand preferences. This study reports hand preferences in the manipulation of joysticks by 2 rhesus monkeys and 3 chimpanzees. Reach data were also collected for comparison with preference data for manipulation of the joystick. The data indicated that all 5 subjects demonstrated significant right-hand preferences in manipulating the joystick. In contrast, no significant hand preferences were found for the reach data. Reaction-time data also indicated that the right hand could perform a perceptual-motor task better than the left hand in all 5 subjects. Overall, the data indicate that reach tasks may not be sensitive enough measures to produce reliable hand preferences, whereas tasks that assess fine-motor control produce significant hand preferences.

  6. Enhanced discriminative stimulus effects of Δ9-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys

    PubMed Central

    McMahon, Lance R.

    2016-01-01

    Background Cannabidiol, a therapeutic with potential serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A receptor agonist activity, is the second most prevalent cannabinoid in Cannabis after Δ9-THC. The extent to which cannabidiol modifies the effects of Δ9-THC has not been firmly established, especially with respect to abuse-related effects in rhesus monkeys where previously antagonistic interactions have been reported for some behavioral outcomes. Methods Cannabidiol and the 5-HT1A receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) were tested in two separate discrimination assays in rhesus monkeys. One group (n=6) discriminated Δ9-tetrahydrocannabinol (Δ9-THC; 0.1 mg/kg i.v.); a second group (n=6) discriminated the cannabinoid antagonist rimonabant (1 mg/kg i.v.) while receiving Δ9-THC daily (1 mg/kg/12 h s.c.). Responding was maintained under a fixed ratio 5 schedule of stimulus-shock termination. Results Both training drugs dose-dependently increased the percentage of responses on the respective drug-associated levers. Cannabidiol (up to 17.8 mg/kg) and 8-OH-DPAT (up to 0.178 mg/kg) did not substitute for either training drug; however, both significantly increased the potency of Δ9-THC to produce discriminative stimulus effects. Moreover, 8-OH-DPAT significantly attenuated the discriminative stimulus effects of rimonabant, whereas cannabidiol did not modify the rimonabant discriminative stimulus. Conclusions These results, which are consistent with cannabidiol lacking CB1 receptor agonist or antagonist activity in vivo, demonstrate enhancement of the effects of Δ9-THC by cannabidiol, albeit at cannabidiol amounts larger than those in Cannabis or cannabidiol-based therapeutics (nabiximols). In addition to showing that cannabidiol and a 5-HT1A receptor agonist have overlapping behavioral effects, the current results suggest that 5-HT1A agonism enhances the CB1 receptor-mediated effects of Δ9-THC. PMID:27289270

  7. Enhanced discriminative stimulus effects of Δ(9)-THC in the presence of cannabidiol and 8-OH-DPAT in rhesus monkeys.

    PubMed

    McMahon, Lance R

    2016-08-01

    Cannabidiol, a therapeutic with potential serotonin (5-hydroxytryptamine; 5-HT) 5-HT1A receptor agonist activity, is the second most prevalent cannabinoid in Cannabis after Δ(9)-THC. The extent to which cannabidiol modifies the effects of Δ(9)-THC has not been firmly established, especially with respect to abuse-related effects in rhesus monkeys where previously antagonistic interactions have been reported for some behavioral outcomes. Cannabidiol and the 5-HT1A receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT) were tested in two separate discrimination assays in rhesus monkeys. One group (n=6) discriminated Δ(9)-tetrahydrocannabinol (Δ(9)-THC; 0.1mg/kg i.v.); a second group (n=6) discriminated the cannabinoid antagonist rimonabant (1mg/kg i.v.) while receiving Δ(9)-THC daily (1mg/kg/12hs.c.). Responding was maintained under a fixed ratio 5 schedule of stimulus-shock termination. Both training drugs dose-dependently increased the percentage of responses on the respective drug-associated levers. Cannabidiol (up to 17.8mg/kg) and 8-OH-DPAT (up to 0.178mg/kg) did not substitute for either training drug; however, both significantly increased the potency of Δ(9)-THC to produce discriminative stimulus effects. Moreover, 8-OH-DPAT significantly attenuated the discriminative stimulus effects of rimonabant, whereas cannabidiol did not modify the rimonabant discriminative stimulus. These results, which are consistent with cannabidiol lacking CB1 receptor agonist or antagonist activity in vivo, demonstrate enhancement of the effects of Δ(9)-THC by cannabidiol, albeit at cannabidiol amounts larger than those in Cannabis or cannabidiol-based therapeutics (nabiximols). In addition to showing that cannabidiol and a 5-HT1A receptor agonist have overlapping behavioral effects, the current results suggest that 5-HT1A agonism enhances the CB1 receptor-mediated effects of Δ(9)-THC. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. Transcriptome analyses of rhesus monkey preimplantation embryos reveal a reduced capacity for DNA double-strand break repair in primate oocytes and early embryos

    PubMed Central

    Wang, Xinyi; Liu, Denghui; He, Dajian; Suo, Shengbao; Xia, Xian; He, Xiechao; Han, Jing-Dong J.; Zheng, Ping

    2017-01-01

    Preimplantation embryogenesis encompasses several critical events including genome reprogramming, zygotic genome activation (ZGA), and cell-fate commitment. The molecular basis of these processes remains obscure in primates in which there is a high rate of embryo wastage. Thus, understanding the factors involved in genome reprogramming and ZGA might help reproductive success during this susceptible period of early development and generate induced pluripotent stem cells with greater efficiency. Moreover, explaining the molecular basis responsible for embryo wastage in primates will greatly expand our knowledge of species evolution. By using RNA-seq in single and pooled oocytes and embryos, we defined the transcriptome throughout preimplantation development in rhesus monkey. In comparison to archival human and mouse data, we found that the transcriptome dynamics of monkey oocytes and embryos were very similar to those of human but very different from those of mouse. We identified several classes of maternal and zygotic genes, whose expression peaks were highly correlated with the time frames of genome reprogramming, ZGA, and cell-fate commitment, respectively. Importantly, comparison of the ZGA-related network modules among the three species revealed less robust surveillance of genomic instability in primate oocytes and embryos than in rodents, particularly in the pathways of DNA damage signaling and homology-directed DNA double-strand break repair. This study highlights the utility of monkey models to better understand the molecular basis for genome reprogramming, ZGA, and genomic stability surveillance in human early embryogenesis and may provide insights for improved homologous recombination-mediated gene editing in monkey. PMID:28223401

  9. Developmental consequences of behavioral inhibition: a model in rhesus monkeys (Macaca mulatta).

    PubMed

    Chun, Katie; Capitanio, John P

    2016-11-01

    In children, behavioral inhibition is characterized by a disposition to withdraw in the presence of strangers and novel situations. Later in life, behavioral inhibition can result in an increased risk for anxiety and depression and a decrease in social behavior. We selected rhesus monkeys that, during infancy, showed evidence of behavioral inhibition in response to separation, and contrasted them with non-inhibited peers. To understand the development of behavioral inhibition at juvenile age, we collected behavioral data in response to relocation; in response to a human intruder challenge; and in naturalistic outdoor field corrals. At 4 years of age (young adulthood), we again collected behavioral data in the outdoor field corrals to understand the adult social consequences of behavioral inhibition. We also included sex, dominance rank, and number of available kin in our analyses. Finally, to understand the consistency in behavior in behaviorally inhibited animals, we conducted exploratory analyses contrasting behaviorally inhibited animals that showed high vs. low durations of non-social behaviors as adults. At juvenile age, behaviorally inhibited animals continued to show behavioral differences in the novel testing room and during the human intruder challenge, generally showing evidence of greater anxiety and emotionality compared to non-inhibited controls. In their outdoor corrals, behaviorally inhibited juveniles spent more time alone and less time in proximity and grooming with mother and other adult females. In young adulthood, we found that behavioral inhibition was not related to time spent alone. We did find that duration of time alone in adulthood was related to time alone exhibited as juveniles; sex, dominance rank, or the number of kin were not influential in adult non-social duration, either as main effects or as moderators. Finally, exploratory analyses revealed that behaviorally inhibited females that were more sociable (less time spent alone) as

  10. Aggressive temperament predicts ethanol self-administration in late adolescent male and female rhesus macaques

    PubMed Central

    McClintick, Megan N.; Grant, Kathleen A.

    2017-01-01

    Rationale Anxiety and aggression are associated with ethanol self-administration, but these behaviors can serve as either risk factors for or consequences of heavy drinking in rodents and humans. Baseline levels of aggressive-like and anxious-like behavior in non-human primates have not yet been characterized in relation to future or prior ethanol intake. Objective To test the association between temperament at baseline with future ethanol self-administration in late adolescent male (n=21) and female (n=11) rhesus monkeys. Methods Shortly after entering the laboratory and before exposure to ethanol, the Human Intruder Test (HIT) and the Novel Object Test (NOT) were used to determine baseline anxious-like and aggressive-like behavior in age-matched male and female rhesus monkeys (Macaca mulatta). The monkeys were induced to drink ethanol 4% (w/v) using a schedule-induced polydipsia procedure, followed by “open-access” ethanol self-administration in which the monkeys were allowed a choice of water or 4% ethanol (w/v) for 22 hours/day (h/d) for 52 weeks. Results Aggressive monkeys self-administered more ethanol and attained higher Blood Ethanol Concentrations (BECs). No significant differences in ethanol intakes or BECs were found between anxious and non-anxious monkeys or between behaviorally inhibited and non-inhibited monkeys. Baseline aggressive behavior positively correlated with ethanol intake and intoxication. Conclusions Baseline reactive aggression was associated with higher future ethanol intake and intoxication. While significant sex differences in HIT reactivity were observed, the relationship between aggression and ethanol drinking was observed across sex and is not sex-specific. PMID:27627910

  11. Contractile properties of rat, rhesus monkey, and human type I muscle fibers

    NASA Technical Reports Server (NTRS)

    Widrick, J. J.; Romatowski, J. G.; Karhanek, M.; Fitts, R. H.

    1997-01-01

    It is well known that skeletal muscle intrinsic maximal shortening velocity is inversely related to species body mass. However, there is uncertainty regarding the relationship between the contractile properties of muscle fibers obtained from commonly studied laboratory animals and those obtained from humans. In this study we determined the contractile properties of single chemically skinned fibers prepared from rat, rhesus monkey, and human soleus and gastrocnemius muscle samples under identical experimental conditions. All fibers used for analysis expressed type I myosin heavy chain as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Allometric coefficients for type I fibers from each muscle indicated that there was little change in peak tension (force/fiber cross-sectional area) across species. In contrast, both soleus and gastrocnemius type I fiber maximal unloaded shortening velocity (Vo), the y-intercept of the force-velocity relationship (Vmax), peak power per unit fiber length, and peak power normalized for fiber length and cross-sectional area were all inversely related to species body mass. The present allometric coefficients for soleus fiber Vo (-0.18) and Vmax (-0.11) are in good agreement with published values for soleus fibers obtained from common laboratory and domesticated mammals. Taken together, these observations suggest that the Vo of slow fibers from quadrupeds and humans scale similarly and can be described by the same quantitative relationships. These findings have implications in the design and interpretation of experiments, especially those that use small laboratory mammals as a model of human muscle function.

  12. Causal effect of disconnection lesions on interhemispheric functional connectivity in rhesus monkeys

    PubMed Central

    O’Reilly, Jill X.; Croxson, Paula L.; Jbabdi, Saad; Sallet, Jerome; Noonan, MaryAnn P.; Mars, Rogier B.; Browning, Philip G.F.; Wilson, Charles R. E.; Mitchell, Anna S.; Miller, Karla L.; Rushworth, Matthew F. S.; Baxter, Mark G.

    2013-01-01

    In the absence of external stimuli or task demands, correlations in spontaneous brain activity (functional connectivity) reflect patterns of anatomical connectivity. Hence, resting-state functional connectivity has been used as a proxy measure for structural connectivity and as a biomarker for brain changes in disease. To relate changes in functional connectivity to physiological changes in the brain, it is important to understand how correlations in functional connectivity depend on the physical integrity of brain tissue. The causal nature of this relationship has been called into question by patient data suggesting that decreased structural connectivity does not necessarily lead to decreased functional connectivity. Here we provide evidence for a causal but complex relationship between structural connectivity and functional connectivity: we tested interhemispheric functional connectivity before and after corpus callosum section in rhesus monkeys. We found that forebrain commissurotomy severely reduced interhemispheric functional connectivity, but surprisingly, this effect was greatly mitigated if the anterior commissure was left intact. Furthermore, intact structural connections increased their functional connectivity in line with the hypothesis that the inputs to each node are normalized. We conclude that functional connectivity is likely driven by corticocortical white matter connections but with complex network interactions such that a near-normal pattern of functional connectivity can be maintained by just a few indirect structural connections. These surprising results highlight the importance of network-level interactions in functional connectivity and may cast light on various paradoxical findings concerning changes in functional connectivity in disease states. PMID:23924609

  13. The Effect of Age on Optic Nerve Axon Counts, SDOCT Scan Quality, and Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in Rhesus Monkeys

    PubMed Central

    Fortune, Brad; Reynaud, Juan; Cull, Grant; Burgoyne, Claude F.; Wang, Lin

    2014-01-01

    Purpose To evaluate the effect of age on optic nerve axon counts, spectral-domain optical coherence tomography (SDOCT) scan quality, and peripapillary retinal nerve fiber layer thickness (RNFLT) measurements in healthy monkey eyes. Methods In total, 83 healthy rhesus monkeys were included in this study (age range: 1.2–26.7 years). Peripapillary RNFLT was measured by SDOCT. An automated algorithm was used to count 100% of the axons and measure their cross-sectional area in postmortem optic nerve tissue samples (N = 46). Simulation experiments were done to determine the effects of optical changes on measurements of RNFLT. An objective, fully-automated method was used to measure the diameter of the major blood vessel profiles within each SDOCT B-scan. Results Peripapillary RNFLT was negatively correlated with age in cross-sectional analysis (P < 0.01). The best-fitting linear model was RNFLT(μm) = −0.40 × age(years) + 104.5 μm (R2 = 0.1, P < 0.01). Age had very little influence on optic nerve axon count; the result of the best-fit linear model was axon count = −1364 × Age(years) + 1,210,284 (R2 < 0.01, P = 0.74). Older eyes lost the smallest diameter axons and/or axons had an increased diameter in the optic nerve of older animals. There was an inverse correlation between age and SDOCT scan quality (R = −0.65, P < 0.0001). Simulation experiments revealed that approximately 17% of the apparent cross-sectional rate of RNFLT loss is due to reduced scan quality associated with optical changes of the aging eye. Another 12% was due to thinning of the major blood vessels. Conclusions RNFLT declines by 4 μm per decade in healthy rhesus monkey eyes. This rate is approximately three times faster than loss of optic nerve axons. Approximately one-half of this difference is explained by optical degradation of the aging eye reducing SDOCT scan quality and thinning of the major blood vessels. Translational Relevance Current models used to predict retinal ganglion cell

  14. Protection of Rhesus Monkeys by a DNA Prime/Poxvirus Boost Malaria Vaccine Depends on Optimal DNA Priming and Inclusion of Blood Stage Antigens

    PubMed Central

    Weiss, Walter R.; Kumar, Anita; Jiang, George; Williams, Jackie; Bostick, Anthony; Conteh, Solomon; Fryauff, David; Aguiar, Joao; Singh, Manmohan; O'Hagan, Derek T.; Ulmer, Jeffery B.; Richie, Thomas L.

    2007-01-01

    Background We have previously described a four antigen malaria vaccine consisting of DNA plasmids boosted by recombinant poxviruses which protects a high percentage of rhesus monkeys against Plasmodium knowlesi (Pk) malaria. This is a multi-stage vaccine that includes two pre-erythrocytic antigens, PkCSP and PkSSP2(TRAP), and two erythrocytic antigens, PkAMA-1 and PkMSP-1(42kD). The present study reports three further experiments where we investigate the effects of DNA dose, timing, and formulation. We also compare vaccines utilizing only the pre-erythrocytic antigens with the four antigen vaccine. Methodology In three experiments, rhesus monkeys were immunized with malaria vaccines using DNA plasmid injections followed by boosting with poxvirus vaccine. A variety of parameters were tested, including formulation of DNA on poly-lactic co-glycolide (PLG) particles, varying the number of DNA injections and the amount of DNA, varying the interval between the last DNA injection to the poxvirus boost from 7 to 21 weeks, and using vaccines with from one to four malaria antigens. Monkeys were challenged with Pk sporozoites given iv 2 to 4 weeks after the poxvirus injection, and parasitemia was measured by daily Giemsa stained blood films. Immune responses in venous blood samples taken after each vaccine injection were measured by ELIspot production of interferon-γ, and by ELISA. Conclusions 1) the number of DNA injections, the formulation of the DNA plasmids, and the interval between the last DNA injection and the poxvirus injection are critical to vaccine efficacy. However, the total dose used for DNA priming is not as important; 2) the blood stage antigens PkAMA-1 and PkMSP-1 were able to protect against high parasitemias as part of a genetic vaccine where antigen folding is not well defined; 3) immunization with PkSSP2 DNA inhibited immune responses to PkCSP DNA even when vaccinations were given into separate legs; and 4) in a counter-intuitive result, higher

  15. Social Communication and Vocal Recognition in Free-Ranging Rhesus Monkeys

    NASA Astrophysics Data System (ADS)

    Rendall, Christopher Andrew

    Kinship and individual identity are key determinants of primate sociality, and the capacity for vocal recognition of individuals and kin is hypothesized to be an important adaptation facilitating intra-group social communication. Research was conducted on adult female rhesus monkeys on Cayo Santiago, Puerto Rico to test this hypothesis for three acoustically distinct calls characterized by varying selective pressures on communicating identity: coos (contact calls), grunts (close range social calls), and noisy screams (agonistic recruitment calls). Vocalization playback experiments confirmed a capacity for both individual and kin recognition of coos, but not screams (grunts were not tested). Acoustic analyses, using traditional spectrographic methods as well as linear predictive coding techniques, indicated that coos (but not grunts or screams) were highly distinctive, and that the effects of vocal tract filtering--formants --contributed more to statistical discriminations of both individuals and kin groups than did temporal or laryngeal source features. Formants were identified from very short (23 ms.) segments of coos and were stable within calls, indicating that formant cues to individual and kin identity were available throughout a call. This aspect of formant cues is predicted to be an especially important design feature for signaling identity efficiently in complex acoustic environments. Results of playback experiments involving manipulated coo stimuli provided preliminary perceptual support for the statistical inference that formant cues take precedence in facilitating vocal recognition. The similarity of formants among female kin suggested a mechanism for the development of matrilineal vocal signatures from the genetic and environmental determinants of vocal tract morphology shared among relatives. The fact that screams --calls strongly expected to communicate identity--were not individually distinctive nor recognized suggested the possibility that their

  16. Inhaled oxytocin amplifies both vicarious reinforcement and self reinforcement in rhesus macaques (Macaca mulatta)

    PubMed Central

    Chang, Steve W. C.; Barter, Joseph W.; Ebitz, R. Becket; Watson, Karli K.; Platt, Michael L.

    2012-01-01

    People attend not only to their own experiences, but also to the experiences of those around them. Such social awareness profoundly influences human behavior by enabling observational learning, as well as by motivating cooperation, charity, empathy, and spite. Oxytocin (OT), a neurosecretory hormone synthesized by hypothalamic neurons in the mammalian brain, can enhance affiliation or boost exclusion in different species in distinct contexts, belying any simple mechanistic neural model. Here we show that inhaled OT penetrates the CNS and subsequently enhances the sensitivity of rhesus macaques to rewards occurring to others as well as themselves. Roughly 2 h after inhaling OT, monkeys increased the frequency of prosocial choices associated with reward to another monkey when the alternative was to reward no one. OT also increased attention to the recipient monkey as well as the time it took to render such a decision. In contrast, within the first 2 h following inhalation, OT increased selfish choices associated with delivery of reward to self over a reward to the other monkey, without affecting attention or decision latency. Despite the differences in species typical social behavior, exogenous, inhaled OT causally promotes social donation behavior in rhesus monkeys, as it does in more egalitarian and monogamous ones, like prairie voles and humans, when there is no perceived cost to self. These findings potentially implicate shared neural mechanisms. PMID:22215593

  17. Synthesis, characterization, and first successful monkey imaging studies of metabotropic glutamate receptor subtype 5 (mGluR5) PET radiotracers.

    PubMed

    Hamill, Terence G; Krause, Stephen; Ryan, Christine; Bonnefous, Celine; Govek, Steve; Seiders, T Jon; Cosford, Nicholas D P; Roppe, Jeffrey; Kamenecka, Ted; Patel, Shil; Gibson, Raymond E; Sanabria, Sandra; Riffel, Kerry; Eng, Waisi; King, Christopher; Yang, Xiaoqing; Green, Mitchell D; O'Malley, Stacey S; Hargreaves, Richard; Burns, H Donald

    2005-06-15

    Three metabotropic glutamate receptor subtype 5 (mGluR5) PET tracers have been labeled with either carbon-11 or fluorine-18 and their in vitro and in vivo behavior in rhesus monkey has been characterized. Each of these tracers share the common features of high affinity for mGluR5 (0.08-0.23 nM vs. rat mGluR5) and moderate lipophilicity (log P 2.8-3.4). Compound 1b was synthesized using a Suzuki or Stille coupling reaction with [11C]MeI. Compounds 2b and 3b were synthesized by a SNAr reaction using a 3-chlorobenzonitrile precursor. Autoradiographic studies in rhesus monkey brain slices using 2b and 3b showed specific binding in cortex, caudate, putamen, amygdala, hippocampus, most thalamic nuclei, and lower binding in the cerebellum. PET imaging studies in monkey showed that all three tracers readily enter the brain and provide an mGluR5-specific signal in all gray matter regions, including the cerebellum. The specific signal observed in the cerebellum was confirmed by the autoradiographic studies and saturation binding experiments that showed tracer binding in the cerebellum of rhesus monkeys. In vitro metabolism studies using the unlabeled compounds showed that 1a, 2a, and 3a are metabolized slower by human liver microsomes than by monkey liver microsomes. In vivo metabolism studies showed 3b to be long-lived in rhesus plasma with only one other more polar metabolite observed. (c) 2005 Wiley-Liss, Inc.

  18. The frontal eye fields limit the capacity of visual short-term memory in rhesus monkeys.

    PubMed

    Lee, Kyoung-Min; Ahn, Kyung-Ha

    2013-01-01

    The frontal eye fields (FEF) in rhesus monkeys have been implicated in visual short-term memory (VSTM) as well as control of visual attention. Here we examined the importance of the area in the VSTM capacity and the relationship between VSTM and attention, using the chemical inactivation technique and multi-target saccade tasks with or without the need of target-location memory. During FEF inactivation, serial saccades to targets defined by color contrast were unaffected, but saccades relying on short-term memory were impaired when the target count was at the capacity limit of VSTM. The memory impairment was specific to the FEF-coded retinotopic locations, and subject to competition among targets distributed across visual fields. These results together suggest that the FEF plays a crucial role during the entry of information into VSTM, by enabling attention deployment on targets to be remembered. In this view, the memory capacity results from the limited availability of attentional resources provided by FEF: The FEF can concurrently maintain only a limited number of activations to register the targets into memory. When lesions render part of the area unavailable for activation, the number would decrease, further reducing the capacity of VSTM.

  19. Kinetic analysis of interactions of paraoxon and oximes with human, Rhesus monkey, swine, rabbit, rat and guinea pig acetylcholinesterase.

    PubMed

    Worek, Franz; Aurbek, Nadine; Wille, Timo; Eyer, Peter; Thiermann, Horst

    2011-01-15

    Previous in vitro studies showed marked species differences in the reactivating efficiency of oximes between human and animal acetylcholinesterase (AChE) inhibited by organophosphorus (OP) nerve agents. These findings provoked the present in vitro study which was designed to determine the inhibition, aging, spontaneous and oxime-induced reactivation kinetics of the pesticide paraoxon, serving as a model compound for diethyl-OP, and the oximes obidoxime, pralidoxime, HI 6 and MMB-4 with human, Rhesus monkey, swine, rabbit, rat and guinea pig erythrocyte AChE. Comparable results were obtained with human and monkey AChE. Differences between human, swine, rabbit, rat and guinea pig AChE were determined for the inhibition and reactivation kinetics. A six-fold difference of the inhibitory potency of paraoxon with human and guinea pig AChE was recorded while only moderate differences of the reactivation constants between human and animal AChE were determined. Obidoxime was by far the most effective reactivator with all tested species. Only minor species differences were found for the aging and spontaneous reactivation kinetics. The results of the present study underline the necessity to determine the inhibition, aging and reactivation kinetics in vitro as a basis for the development of meaningful therapeutic animal models, for the proper assessment of in vivo animal data and for the extrapolation of animal data to humans. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  20. Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys.

    PubMed

    Hutsell, Blake A; Negus, S Stevens; Banks, Matthew L

    2016-11-01

    Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined. Continuous 21-day treatments with ramping doses of d-amphetamine (days 1-7: 0.032mg/kg/h; days 8-21: 0.1mg/kg/h, i.v.) or risperidone (days 1-7: 0.001mg/kg/h; days 8-14: 0.0032mg/kg/h; days 15-21: 0.0056mg/kg/h, i.v.) were administered to rhesus monkeys (n=4) with daily access to two types of cocaine self-administration sessions: (1) a 2-h 'choice' session with concurrent availability of 1-g food pellets and intravenous cocaine injections (0-0.1mg/kg per injection) and (2) a 20-h 'extended-access' session with 0.1mg/kg per injection cocaine availability. Total daily cocaine intake increased >6-fold during extended cocaine access. d-Amphetamine significantly decreased total cocaine intake, but not cocaine vs food choice. In contrast, risperidone did not significantly alter either total cocaine intake or cocaine vs. food choice. These results confirm and extend previous results supporting treatment effectiveness for monoamine releasers, but not dopamine antagonists, to reduce cocaine self-administration. Moreover, these results suggest amphetamine treatment efficacy to decrease preclinical cocaine vs. food choice may depend upon cocaine access conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Effects of 21-day d-amphetamine and risperidone treatment on cocaine vs food choice and extended-access cocaine intake in male rhesus monkeys

    PubMed Central

    Hutsell, Blake A.; Negus, S. Stevens; Banks, Matthew L.

    2016-01-01

    Background Clinical trial data suggest amphetamine treatment is most efficacious in moderate to high frequency cocaine users. However, preclinical studies have examined amphetamine treatment effects under relatively limited cocaine access conditions with low to moderate cocaine intakes. This study determined d-amphetamine treatment effects on cocaine self-administration in rhesus monkeys under cocaine access conditions allowing for high daily cocaine intake. For comparison and as a negative control, treatment effects with the antipsychotic risperidone were also examined. Methods Continuous 21-day treatments with ramping doses of d-amphetamine (days 1–7: 0.032 mg/kg/h; days 8–21: 0.1 mg/kg/h, i.v.) or risperidone (days 1–7: 0.001 mg/kg/h; days 8–14: 0.0032 mg/kg/h; days 15–21: 0.0056 mg/kg/h, i.v.) were administered to rhesus monkeys (n = 4) with daily access to two types of cocaine self-administration sessions: (1) a 2-h ‘choice’ session with concurrent availability of 1-g food pellets and intravenous cocaine injections (0–0.1 mg/kg per injection) and (2) a 20-h ‘extended-access’ session with 0.1 mg/kg per injection cocaine availability. Results Total daily cocaine intake increased >6-fold during extended cocaine access. d-Amphetamine significantly decreased total cocaine intake, but not cocaine vs food choice. In contrast, risperidone did not significantly alter either total cocaine intake or cocaine vs. food choice. Conclusions These results confirm and extend previous results supporting treatment effectiveness for monoamine releasers, but not dopamine antagonists, to reduce cocaine self-administration. Moreover, these results suggest amphetamine treatment efficacy to decrease preclinical cocaine vs. food choice may depend upon cocaine access conditions. PMID:27615401

  2. The Toxicity of Soman in the African Green Monkey (Chlorocebus aethiops)

    DTIC Science & Technology

    2007-01-01

    M., and Mestries, 1. C. 1998. Nerve agent poisoning in primates: antilethal, anti -epileptic and neuroprotective effects of GK-11. Arch. Toxico/. 72...toxicity in African green monkeys (Chlorocebus aethiops) and is the first step in exploring the suitability of this species as a model for nerve agent ...rhesus monkey (Macaca mulatta) has traditionally served as the NHP research species of choice to assess nerve agent toxicity and the effectiveness of

  3. Adrenal hyperandrogenism is induced by fetal androgen excess in a rhesus monkey model of polycystic ovary syndrome.

    PubMed

    Zhou, Rao; Bird, Ian M; Dumesic, Daniel A; Abbott, David H

    2005-12-01

    Adrenal androgen excess is found in approximately 25-60% of women with polycystic ovary syndrome (PCOS), but the mechanisms underlying PCOS-related adrenal androgen excess are unclear. The objective of this study was to determine whether adrenal androgen excess is manifest in a nonhuman primate model for PCOS. Six prenatally androgenized (PA) and six control female rhesus monkeys of similar age, body weight, and body mass index were studied during d 2-6 of two menstrual cycles or anovulatory 30-d periods. Predexamethasone adrenal steroid levels were assessed in the first cycle (cycle 1). In a subsequent cycle (cycle 2), occurring one to three cycles after cycle 1, adrenal steroids were determined 14.5-16.0 h after an i.m. injection of 0.5 mg/kg dexamethasone (postdexamethasone levels) and after an i.v. injection of 50 microg ACTH-(1-39). Both before and after dexamethasone, serum levels of dehydroepiandrosterone (DHEA) in PA females exceeded those in controls. After ACTH injection, PA females exhibited higher circulating levels of DHEA, androstenedione, and corticosterone but comparable levels of 17alpha-hydroxyprogesterone, cortisol, the sulfoconjugate of DHEA, and testosterone compared with controls. Enhanced basal and ACTH-stimulated adrenal androgen levels in PA female monkeys may reflect up-regulation of 17,20 lyase activity in the adrenal zona reticularis, causing adrenal androgen excess comparable with that found in PCOS women with adrenal androgen excess. These findings open the possibility that PCOS adrenal hyperandrogenism may have its origins in fetal androgen excess reprogramming of adrenocortical function.

  4. Mathematical Modeling of Serum 13C-Retinol in Captive Rhesus Monkeys Provides New Insights on Hypervitaminosis A1–3

    PubMed Central

    Escaron, Anne L.; Green, Michael H.; Howe, Julie A.; Tanumihardjo, Sherry A.

    2009-01-01

    Hypervitaminosis A is increasingly a public health concern, and thus noninvasive quantitative methods merit exploration. In this study, we applied the 13C-retinol isotope dilution test to a nonhuman primate model with excessive liver stores. After baseline serum chemistries, rhesus macaques (Macaca mulatta; n = 16) were administered 3.5 μmol 13C2-retinyl acetate. Blood was drawn at baseline, 5 h, and 2, 4, 7, 14, 21, and 28 d following the dose. Liver biopsies were collected 7 d before and 2 d after dosing (n = 4) and at 7, 14, and 28 d (n = 4/time) after dosing. Serum and liver were analyzed by HPLC and GC-combustion-isotope ratio MS for retinol and its enrichment, respectively. Model-based compartmental analysis was applied to serum data. Lactate dehydrogenase was elevated in 50% of the monkeys. Total body reserves (TBR) of vitamin A (VA) were calculated at 28 d. Predicted TBR (3.52 ± 2.01 mmol VA) represented measured liver stores (4.56 ± 1.38 mmol VA; P = 0.124). Predicted liver VA concentrations (13.3 ± 9.7 μmol/g) were similar to measured liver VA concentrations (16.4 ± 5.3 μmol/g). The kinetic models predict that 27–52% of extravascular VA is exchanging with serum in hypervitaminotic A monkeys. The test correctly diagnosed hypervitaminosis A in all monkeys, i.e. 100% sensitivity. Stable isotope techniques have important public health potential for the classification of VA status, including hypervitaminosis, because no other technique besides invasive liver biopsies, correctly identifies excessive liver VA stores. PMID:19710158

  5. 3B11-N, a monoclonal antibody against MERS-CoV, reduces lung pathology in rhesus monkeys following intratracheal inoculation of MERS-CoV Jordan-n3/2012

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Johnson, Reed F., E-mail: johnsonreed@mail.nih.gov; Bagci, Ulas; Center for Research in Computer Vision

    Middle East Respiratory Syndrome Coronavirus (MERS-CoV) was identified in 2012 as the causative agent of a severe, lethal respiratory disease occurring across several countries in the Middle East. To date there have been over 1600 laboratory confirmed cases of MERS-CoV in 26 countries with a case fatality rate of 36%. Given the endemic region, it is possible that MERS-CoV could spread during the annual Hajj pilgrimage, necessitating countermeasure development. In this report, we describe the clinical and radiographic changes of rhesus monkeys following infection with 5×10{sup 6} PFU MERS-CoV Jordan-n3/2012. Two groups of NHPs were treated with either a humanmore » anti-MERS monoclonal antibody 3B11-N or E410-N, an anti-HIV antibody. MERS-CoV Jordan-n3/2012 infection resulted in quantifiable changes by computed tomography, but limited other clinical signs of disease. 3B11-N treated subjects developed significantly reduced lung pathology when compared to infected, untreated subjects, indicating that this antibody may be a suitable MERS-CoV treatment. - Highlights: • MERS-CoV Jordan-n3/2012 challenge of rhesus monkeys results in a mild disease. • CT can be used to monitor disease progression to aid models of human disease. • Treatment with the human monoclonal antibody 3B11-N resulted in decreased disease.« less

  6. Comparison of Object Recognition Behavior in Human and Monkey

    PubMed Central

    Rajalingham, Rishi; Schmidt, Kailyn

    2015-01-01

    Although the rhesus monkey is used widely as an animal model of human visual processing, it is not known whether invariant visual object recognition behavior is quantitatively comparable across monkeys and humans. To address this question, we systematically compared the core object recognition behavior of two monkeys with that of human subjects. To test true object recognition behavior (rather than image matching), we generated several thousand naturalistic synthetic images of 24 basic-level objects with high variation in viewing parameters and image background. Monkeys were trained to perform binary object recognition tasks on a match-to-sample paradigm. Data from 605 human subjects performing the same tasks on Mechanical Turk were aggregated to characterize “pooled human” object recognition behavior, as well as 33 separate Mechanical Turk subjects to characterize individual human subject behavior. Our results show that monkeys learn each new object in a few days, after which they not only match mean human performance but show a pattern of object confusion that is highly correlated with pooled human confusion patterns and is statistically indistinguishable from individual human subjects. Importantly, this shared human and monkey pattern of 3D object confusion is not shared with low-level visual representations (pixels, V1+; models of the retina and primary visual cortex) but is shared with a state-of-the-art computer vision feature representation. Together, these results are consistent with the hypothesis that rhesus monkeys and humans share a common neural shape representation that directly supports object perception. SIGNIFICANCE STATEMENT To date, several mammalian species have shown promise as animal models for studying the neural mechanisms underlying high-level visual processing in humans. In light of this diversity, making tight comparisons between nonhuman and human primates is particularly critical in determining the best use of nonhuman primates to

  7. Conceptual thresholds for same and different in old-(Macaca mulatta) and new-world (Cebus apella) monkeys

    PubMed Central

    Flemming, Timothy M.

    2011-01-01

    Learning of the relational same/different (S/D) concept has been demonstrated to be largely dependent upon stimulus sets containing more than two items for pigeons and old-world monkeys. Stimulus arrays containing several images for use in same/different discrimination procures (e.g. 16 identical images vs. 16 nonidentical images) have been shown to facilitate and even be necessary for learning of relational concepts (Flemming, Beran & Washburn, 2007; Wasserman, Young & Fagot, 2001; Young, Wasserman & Garner, 1997). In the present study, we investigate the threshold at which a new world primate, the capuchin (Cebus apella) may be able to make such a discrimination. Utilizing a method of increasing entropy, rather than conventional procedures of decreasing entropy, we demonstrate unique evidence that capuchin monkeys are readily capable of making 2-item relational S/D conditional discriminations. In another experiment, we examine the supposed level of difficulty in making S/D discriminations by rhesus monkeys (Macaca mulatta). Whereas pigeons (Columba livia) and baboons (Papio papio) have shown marked difficulty simultaneously discriminating same from different arrays at all when composed of fewer than 8 items each, rhesus monkeys seem to understand that pairs of stimuli connote sameness and difference just the same (Flemming et al., 2007). With sustained accurate performance of 2-item S/D discriminations, both experienced and task-naïve rhesus monkeys appear quite certain in their conceptual knowledge of same and different. We conclude that learning of the same/different relational concept may be less dependent upon high levels of entropy contrast than originally hypothesized for nonhuman primates. PMID:21238555

  8. Pharmacological inhibition of PI3K reduces adiposity and metabolic syndrome in obese mice and rhesus monkeys.

    PubMed

    Ortega-Molina, Ana; Lopez-Guadamillas, Elena; Mattison, Julie A; Mitchell, Sarah J; Muñoz-Martin, Maribel; Iglesias, Gema; Gutierrez, Vincent M; Vaughan, Kelli L; Szarowicz, Mark D; González-García, Ismael; López, Miguel; Cebrián, David; Martinez, Sonia; Pastor, Joaquin; de Cabo, Rafael; Serrano, Manuel

    2015-04-07

    Genetic inhibition of PI3K signaling increases energy expenditure, protects from obesity and metabolic syndrome, and extends longevity. Here, we show that two pharmacological inhibitors of PI3K, CNIO-PI3Ki and GDC-0941, decrease the adiposity of obese mice without affecting their lean mass. Long-term treatment of obese mice with low doses of CNIO-PI3Ki reduces body weight until reaching a balance that is stable for months as long as the treatment continues. CNIO-PI3Ki treatment also ameliorates liver steatosis and decreases glucose serum levels. The above observations have been recapitulated in independent laboratories and using different oral formulations of CNIO-PI3Ki. Finally, daily oral treatment of obese rhesus monkeys for 3 months with low doses of CNIO-PI3Ki decreased their adiposity and lowered their serum glucose levels, in the absence of detectable toxicities. Therefore, pharmacological inhibition of PI3K is an effective and safe anti-obesity intervention that could reverse the negative effects of metabolic syndrome in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Neonatal Amygdala Lesions Alter Mother–Infant Interactions in Rhesus Monkeys Living in a Species-Typical Social Environment

    PubMed Central

    Stephens, Shannon B.Z.; Sanchez, Mar; Bachevalier, Jocelyne; Wallen, Kim

    2015-01-01

    The current study examined the effects of neonatal amygdala lesions on mother–infant interactions in rhesus monkeys reared in large species-typical social groups. Focal observations of mother–infant interactions were collected in their social group for the first 12 months postpartum on infants that had received amygdala lesions (Neo-A) at 24–25 days of age and control infants. Early amygdala lesions resulted in subtle behavioral alterations. Neo-A females exhibited earlier emergence of independence from the mother than did control females, spending more time away from their mother, whereas Neo-A males did not. Also, a set of behaviors, including coo vocalizations, time in contact, and time away from the mother, accurately discriminated Neo-A females from control females, but not Neo-A and control males. Data suggest that neonatal amygdalectomy either reduced fear, therefore increasing exploration in females, or reduced the positive reward value of maternal contact. Unlike females, neonatal amygdala lesions had little measurable effects on male mother–infant interactions. The source of this sex difference is unknown. PMID:24986273

  10. Traditional Chinese medicine etiology and pathogenesis of acquired immune deficiency syndrome in simian immunodeficiency virus-infected Chinese rhesus macaques.

    PubMed

    Li, Maoqing; Fu, Linchun; Hu, Yinjie; Zhang, Miaomiao; He, Jinyang; Chen, Zhixi; Chen, Jinyan

    2012-12-01

    To investigate the traditional Chinese Medicine (TCM) etiology and pathogenesis of acquired immune deficiency syndrome (AIDS) by 18-month observation of Chinese rhesus macaques infected with simian immunodeficiency virus (SIV) mac239. Thirty-five healthy Chinese rhesus macaques were divided into a model group (n = 30) and a control group (n = 5). The model was established by inoculating monkeys intravenously with SIVmac239. Changes in TCM symptoms after SIV infection within 18 months were then observed and recorded. Routine blood tests, SIV viral load, T-lymphocyte subsets, plasma triiodothyronine (T3), tetraiodothyronine (T4), adrenocorticotropic hormone (ACTH) and cortisol (Cor) were tested periodically during the experiment. During the acute infection period of SIV, model monkeys temporarily showed clinical symptoms such as diarrhea, dysphoria and slight weight loss. Decrease percentages of CD4+ T-lymphocytes were observed but levels of T3, T4, Cor, and ACTH were relatively unchanged. Monkeys in the model group during the early and middle periods of infection showed no obvious symptoms, except few monkeys exhibited transient diarrhea and reduced food intake. All variables at this stage showed normal fluctuations. In the middle period model group monkeys showed chronic and persistent diarrhea, weight loss, reduced food intake and low levels of T3 and Cor. In the late period, symptoms including emaciation, weight loss, listlessness, crouching in corners and low levels of T3 appeared. The results suggest that the rhesus monkey SIV/SAIDS model can be applied to research on TCM etiology and pathogenesis of AIDS. According to this model, the etiology of disease is the SIV virus. The pathogenesis manifests as the invasion of SIV virus, incubation of the virus, balance between virus and healthy "Qi", damage to spleen and kidney as the disease progressed, exhaustion of vitality and finally the failure of five zang and six fu organs.

  11. A decade of theory of mind research on Cayo Santiago: Insights into rhesus macaque social cognition.

    PubMed

    Drayton, Lindsey A; Santos, Laurie R

    2016-01-01

    Over the past several decades, researchers have become increasingly interested in understanding how primates understand the behavior of others. One open question concerns whether nonhuman primates think about others' behavior in psychological terms, that is, whether they have a theory of mind. Over the last ten years, experiments conducted on the free-ranging rhesus monkeys (Macaca mulatta) living on Cayo Santiago have provided important insights into this question. In this review, we highlight what we think are some of the most exciting results of this body of work. Specifically we describe experiments suggesting that rhesus monkeys may understand some psychological states, such as what others see, hear, and know, but that they fail to demonstrate an understanding of others' beliefs. Thus, while some aspects of theory of mind may be shared between humans and other primates, others capacities are likely to be uniquely human. We also discuss some of the broader debates surrounding comparative theory of mind research, as well as what we think may be productive lines for future research with the rhesus macaques of Cayo Santiago. © 2016 Wiley Periodicals, Inc.

  12. Diet choice, cortisol reactivity, and emotional feeding in socially housed rhesus monkeys.

    PubMed

    Arce, Marilyn; Michopoulos, Vasiliki; Shepard, Kathryn N; Ha, Quynh-Chau; Wilson, Mark E

    2010-11-02

    Chronic psychosocial stress produces an array of adverse health consequences that are highly comorbid, including emotional eating, affective disorders, and metabolic syndrome. The consumption of high caloric diets (HCDs) is thought to provide comfort in the face of unrelenting psychosocial stress. Using social subordination in female rhesus monkeys as a model of continual exposure to daily stressors in women, we tested the hypothesis that subordinate females would consume significantly more calories from a HCD compared to dominant females, and this pattern of food intake would be associated with reduced cortisol release and reduced frequency of anxiety-like behaviors. Food intake, parameters of cortisol secretion, and socio-emotional behavior were assessed for 3 weeks during a no choice phase when only a low caloric diet (LCD) was available and during a choice condition when both a LCD and HCD were available. While all animals preferred the HCD, subordinate females consumed significantly more of the HCD than did dominant females. A flattening of the diurnal cortisol rhythm and a greater increase in serum cortisol to an acute social separation occurred during the diet choice condition in all females. Furthermore, the rate of anxiety-like behavior progressively declined during the 3-week choice condition in subordinate but not dominant females. These data provide support for the hypothesis that daily exposure to psychosocial stress increases consumption of calorically dense foods. Furthermore, consumption of HCDs may be a metabolic stressor that synergizes with the psychosocial stress of subordination to further increase the consumption of these diets. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Self-administration of (+)-methamphetamine and (+)-pseudoephedrine, alone and combined, by rhesus monkeys.

    PubMed

    Freeman, Kevin B; Wang, Zhixia; Woolverton, William L

    2010-04-01

    (+)-Methamphetamine (MA) is an illicit psychostimulant that can be synthesized from the nonprescription nasal decongestant, (+)-pseudoephedrine (PE). While MA is widely abused, PE appears to have little or no abuse liability in currently available formulations. However, PE produces centrally-mediated dopaminergic effects that are linked to the reinforcing effects of MA and other illicit psychostimulants and has been reported to function as a positive reinforcer in non-human primates. There has yet to be an assessment of the relative reinforcing effects of MA and PE. Therefore, the current study compared the reinforcing potency and strength of MA and PE, alone and combined, in four rhesus monkeys that were allowed to self-administer MA (0.003-0.3 mg/kg/inj), PE (0.1-3.0 mg/kg/inj), or combinations of the two under a progressive-ratio schedule of reinforcement. (+)-Methamphetamine functioned as a positive reinforcer in a dose-dependent manner. (+)-Pseudoephedrine also functioned as a positive reinforcer, but was less potent than MA. There were no differences in maximum injections between MA, PE, or any of the combinations of the two. Dose-addition analysis and the interaction index indicated that combinations of PE and MA were either additive or sub-additive in their reinforcing effects. These results suggest that, while MA is a more potent reinforcer than PE, the two drugs are comparable in terms of reinforcing strength. However, MA and PE do not appear to interact in a manner that enhances their relative reinforcing effects. Published by Elsevier Inc.

  14. Self-administration of (+)-methamphetamine and (+)-pseudoephedrine, alone and combined, by rhesus monkeys

    PubMed Central

    Freeman, Kevin B.; Wang, Zhixia; Woolverton, William L.

    2010-01-01

    (+)-Methamphetamine (MA) is an illicit psychostimulant that can be synthesized from the nonprescription nasal decongestant, (+)-pseudoephedrine (PE). While MA is widely abused, PE appears to have little or no abuse liability in currently available formulations. However, PE produces centrally-mediated dopaminergic effects that are linked to the reinforcing effects of MA and other illicit psychostimulants and has been reported to function as a positive reinforcer in non-human primates. There has yet to be an assessment of the relative reinforcing effects of MA and PE. Therefore, the current study compared the reinforcing potency and strength of MA and PE, alone and combined, in four rhesus monkeys that were allowed to self-administer MA (0.003-0.3 mg/kg/inj), PE (0.1-3.0 mg/kg/inj), or combinations of the two under a progressive-ratio schedule of reinforcement. (+)-Methamphetamine functioned as a positive reinforcer in a dose-dependent manner. (+)-Pseudoephedrine also functioned as a positive reinforcer, but was less potent than MA. There were no differences in maximum injections between MA, PE, or any of the combinations of the two. Dose-addition analysis and the interaction index indicated that combinations of PE and MA were either additive or sub-additive in their reinforcing effects. These results suggest that, while MA is a more potent reinforcer than PE, the two drugs are comparable in terms of reinforcing strength. However, MA and PE do not appear to interact in a manner that enhances their relative reinforcing effects. PMID:20100506

  15. Intrinsic connections and architectonics of posterior parietal cortex in the rhesus monkey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pandya, D.N.; Seltzer, B.

    1982-01-10

    By means of autoradiographic and ablation-degeneration techniques, the intrinsic cortical connections of the posterior parietal cortex in the rhesus monkey were traced and correlated with a reappraisal of cerebral architectonics. Two major rostral-to-caudal connectional sequences exist. One begins in the dorsal postcentral gyrus (area 2) and proceeds, through architectonic divisions of the superior parietal lobule (areas PE and PEc), to a cortical region on the medial surface of the parietal lobe (area PGm). This area has architectonic features similar to those of the caudal inferior parietal lobule (area PG). The second sequence begins in the ventral post/central gyrus (area 2)more » and passes through the rostral inferior parietal lobule (areas PG and PFG) to reach the caudal inferior parietal lobule (area PG). Both the superior parietal lobule and the rostral inferior parietal lobule also send projections to various other zones located in the parietal opercular region, the intraparietal sulcus, and the caudalmost portion of the cingulate sulcus. Areas PGm and PG, on the other hand, project to each other, to the cingulate region, to the caudalmost portion of the superior temporal gyrus, and to the upper bank of the superior temporal sulcus. Finally, a reciprocal sequence of connections, directed from caudal to rostral, links together many of the above-mentioned parietal zones. With regard to the laminar pattern of termination, the rostral-to-caudal connections are primarily distributed in the form of cortical ''columns'' while the caudal-to-rostral connections are found mainly over the first cortical cell layer.« less

  16. Effects of taurodihydrofusidate, a bile salt analogue, on bile formation and biliary lipid secretion in the rhesus monkey.

    PubMed Central

    Beaudoin, M; Carey, M C; Small, D M

    1975-01-01

    Bile salts play a major role in bile formation and biliary lipid secretion. Sodium taurodihydrofusidate (TDHF), a derivative of the antibiotic fusidic acid, closely resembles bile salts in terms of structure, micellar characteristics, and capacity ot solubilize otherwise insolbule lipids. We have therefore studied the biliary secretion of this bile salt analogue and its influence on bile formation and biliary lipid secretion in primates. Alert, unanesthetized female rhesus monkeys prepared with a total biliary fistula were allowed to reach a steady bile salt secretion rate before each study. In three animals (group I),[14C]TDHF was infused intravenously. Most of the compound was secreted rapidly in bile chemically unchanged. The biliary secretion of this drug produced a twofold increase in bile flow; however, the bile salt output was markedly reduced during the infusion. In spite of this reduction, the phospholipid output remained essentially unchanged whereas the cholesterol output increased almost twofold. In five other animals (group II), the effect of TDHF on the bile salt secretion was further investigated by an intravenous infusion of [14C]taurocholate followed by a combined infusion of [14C]taurocholate and TDHF. When TDHF was added to the infusate, a reduction in the [14C]taurocholate output and a progressive rise in the plasma [14C]taurocholate concentration were observed in each animal. An analysis of the data in both groups indicates that (a) the most likely explanation to account for the decreased bile salt output is that the bile salt analogue, TDHF, interfered with bile salt secretion into the biliary canaliculi; (b) TDHF induces a greater secretion of biliary water than was observed with bile salts, an effect consistent with a stimulation of the bile salt-independent canalicular flow; (c) at similar 3alpha-hydroxysteroid secretion rates TDHF caused a significant increase in cholesterol secretion compared to that induced by bile salt. This finding

  17. Ion transport characteristics in rhesus monkey erythrocytes: relationship to age and blood pressure.

    PubMed

    Hennessy, J F; Buckalew, V M; Gruber, K A; Ober, K P; Bullock, B; Hannert, P; Garay, R

    1984-01-01

    Erythrocyte (RBC) ion transport characteristics were examined in six young Rhesus monkeys (RM) age 3.3 +/- .3 (means +/- S.D.) years and seven mature RM 15.4 +/- 1 (means +/- S.D.) years. It was found that the older RM when compared to the younger RM demonstrated significantly elevated mean arterial pressures (MAP) (96 +/- 15 versus 75 +/- 11 mmHg), RBC intracellular sodiums (RBC Nai) (16.2 +/- 4 versus 11 +/- 3 mEq/liter RBC) and NaK ATPase pump rates per RBC (PR) (PR = ouabain sensitive K uptake divided by ouabain binding sites per RBC) (104 +/- 18 versus 83 +/- 18 K+ ions/sec/pump unit). However, it was also found that when the data from both groups were pooled and collectively analyzed a significantly positive correlation could be found between MAP and RBC Nai (p less than .001, r = .82), MAP and PR (p less than .01, r = .67) as well as PR and RBC Nai (p less than .001, r = .76). The fact that positive correlations exist among these parameters, independent of age, would suggest that while MAP, RBC Nai and PR tend to be elevated with advancing age, these abberations are not invariable consequences of age and best reflect the pivotal abberration of rising Nai. While insufficient data exist to account for the rise in Nai and no cause-effect relationship can be established it is clear that rising MAP and PR correlate best with rising Nai.

  18. Early Life Experiences and Telomere Length in Adult Rhesus Monkeys: An Exploratory Study

    PubMed Central

    Schneper, Lisa M.; Brooks-Gunn, Jeanne; Notterman, Daniel A.; Suomi, Stephen J.

    2016-01-01

    Objective Child rearing environments have been associated with morbidity in adult rhesus monkeys. We examine whether such links are also seen with leukocyte telomere length. Methods To determine telomere length in leukocytes, blood was collected from 11 adult females aged seven to ten years who had been exposed to different rearing environments between birth and seven months. Four had been reared with their mothers in typical social groups comprised of other females, their offspring, and 1–2 adult males. The other seven had been reared in either small groups of peers or in individual cages with extensive peer interaction daily. After seven months, all shared a common environment. Results Telomere lengths were longer for those adults who had been reared with their mothers in social groups (median = 16.0 kb, interquartile range = 16.5–15.4) than for those who were reared without their mothers (median = 14.0 kb, interquartile range = 14.3–12.7; 2.2 kb/telomere difference, p<0.027). Conclusions This observation adds to emerging knowledge about early adverse child rearing conditions and their potential for influencing later morbidity. As newborns were randomly assigned to the mother or other rearing conditions, the findings are not confounded by other conditions that co-occur with adverse child rearing environments in humans (e.g., prenatal stress, nutrition and health as well as postnatal nutrition and negative life experiences over and above rearing conditions). PMID:27763985

  19. Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images.

    PubMed

    Chang, Liangtang; Zhang, Shikun; Poo, Mu-Ming; Gong, Neng

    2017-03-21

    Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal.

  20. Full-Field Accommodation in Rhesus Monkeys Measured Using Infrared Photorefraction

    PubMed Central

    He, Lin; Wendt, Mark

    2012-01-01

    Purpose. Full-field photorefraction was measured during accommodation in anesthetized monkeys to better understand the monkey as a model of human accommodation and how accommodation affects off-axis refraction. Methods. A photorefraction camera was rotated on a 30-cm-long rod in a horizontal arc, with the eye at the center of curvature of the arc so that the measurement distance remained constant. The resistance of a potentiometer attached to the rotation center of the rod changed proportionally with the rotation angle. Photorefraction and rotation angle were simultaneously measured at 30 Hz. Trial-lens calibrations were performed on-axis and across the full field in each eye. Full-field refraction measurements were compared using on-axis and full-field calibrations. In five iridectomized monkeys (mean age in years ± SD: 12.8 ± 0.9), full-field refraction was measured before and during carbachol iontophoresis stimulated accommodation, a total of seven times (with one repeat each in two monkeys). Results. Measurements over approximately 20 seconds had <0.1 D of variance and an angular resolution of 0.1°, from at least −30° to 30°. Photorefraction calibrations performed over the full field had a maximum variation in the calibration slopes within one eye of 90%. Applying full-field calibrations versus on-axis calibrations resulted in a decrease in the maximum SDs of the calculated refractions from 1.99 to 0.89 D for relative peripheral refractive error and from 4.68 to 1.99 D for relative accommodation. Conclusions. By applying full-field calibrations, relative accommodation in pharmacologically stimulated monkeys was found to be similar to that reported with voluntary accommodation in humans. PMID:22125278

  1. Clinically Employed Opioid Analgesics Produce Antinociception via μ-δ Opioid Receptor Heteromers in Rhesus Monkeys

    PubMed Central

    2012-01-01

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans. PMID:23019498

  2. Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

    PubMed

    Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

    2012-09-19

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

  3. Maternal and Fetal Pharmacokinetics of Oral Radiolabeled and Authentic Bisphenol A in the Rhesus Monkey

    PubMed Central

    VandeVoort, Catherine A.; Gerona, Roy R.; vom Saal, Frederick S.; Tarantal, Alice F.; Hunt, Patricia A.; Hillenweck, Anne; Zalko, Daniel

    2016-01-01

    The present study was conducted in pregnant rhesus monkeys to determine the rapidity and extent to which BPA reaches the fetal compartment following oral ingestion, and the 24-hr fate of BPA. To assess metabolism changes during the course of pregnancy, we compared BPA biotransformation during the second and third trimesters in the same animals, measuring the levels of sulfated, gluronidated, and free BPA in maternal serum, amniotic fluid, and fetal serum. All animals showed measurable unconjugated and conjugated BPA in the fetal compartment and slow clearance compared to maternal serum. There were higher levels of BPA-G in amniotic fluid at 150 days gestation compared to 100 days gestation, as well as higher levels of BPA-G than BPA-S. We also monitored 3H-BPA (and metabolites) in key tissues and excreta from a mother and fetus and from a non-pregnant female. The elimination of radioactivity was rapid, but residues were still detectable 24 hr after dosing in all tissues analyzed. These data suggest that, in primates, rapid maternal processing of BPA does not alleviate the risk of exposure to the developing fetus. This study elevates concerns about levels of current BPA human exposure from potentially a large number of unknown sources and the risks posed to developing fetuses. PMID:27930651

  4. Accelerated Episodic LH Release Accompanies Blunted Progesterone Regulation in PCOS-like Female Rhesus Monkeys (Macaca mulatta) Exposed to Testosterone During Early-to-Mid Gestation.

    PubMed

    Abbott, David H; Vepraskas, Sarah H; Horton, Teresa H; Terasawa, Ei; Levine, Jon E

    2018-06-15

    Ovarian theca cell hyperandrogenism in women with PCOS is compounded by androgen receptor-mediated impairment of estradiol and progesterone negative feedback regulation of episodic LH release. The resultant LH hypersecretion, likely the product of accelerated episodic release of GnRH from the median eminence of the hypothalamus, hyperstimulates ovarian theca cell steroidogenesis, enabling testosterone (T) and androstenedione excess. Prenatally androgenized female monkeys (PA) exposed to fetal male levels of T during early-to-mid gestation, when adult, demonstrate PCOS-like traits, including high T and LH levels. This study tests the hypothesis that progesterone resistance-associated acceleration in episodic LH release contributes to PA monkey LH excess. 4 PA and 3 regularly cycling, healthy control adult female rhesus monkeys of comparable age and body mass index underwent (1) a 10 h, frequent intravenous sampling assessment for LH episodic release, immediately followed by (2) IV infusion of exogenous GnRH to quantify continuing pituitary LH responsiveness, and subsequently (3) an SC injection of a progesterone receptor antagonist, mifepristone, to examine LH responses to blockade of progesterone-mediated action. Compared to controls, the relatively hyperandrogenic PA females exhibited ~100% increase (p = 0.037) in LH pulse frequency, positive correlation of LH pulse amplitude (p = 0.017) with androstenedione, ~100% greater increase (p = 0.034) in acute (0--10 min) LH responses to exogenous GnRH, and an absence (p = 0.008) of modest LH elevation following acute progesterone receptor blockade suggestive of diminished progesterone negative feedback. Such dysregulation of LH release in PCOS-like monkeys implicates impaired feedback control of episodic release of hypothalamic GnRH reminiscent of PCOS neuroendocrinopathy. 2018 S. Karger AG, Basel.

  5. Social instability and immunity in rhesus monkeys: the role of the sympathetic nervous system.

    PubMed

    Capitanio, John P; Cole, Steven W

    2015-05-26

    Social instability can adversely affect endocrine, immune and health outcomes, and recent evidence suggests that the sympathetic nervous system (SNS) might mediate these effects. We conducted two studies with adult male rhesus monkeys (Macaca mulatta) to understand how social conditions affect measures of SNS activity and immune function. In Experiment 1, animals were socialized in stable social conditions, then were switched to unstable (stressful) social conditions, then were returned to stable conditions. Analysis revealed quadratic effects for measures of behaviour, urinary metabolites of epinephrine and norepinephrine, and expression of immune response genes: as expected, social instability adversely impacted most measures, and the effects remediated upon re-imposition of stable conditions. Cortisol levels were unaffected. In Experiment 2, we used the sympathomimetic drug methamphetamine to challenge the SNS; animals also underwent socialization in stable or unstable groups. Surprisingly, while methamphetamine elevated plasma catecholamines, responses in lymph nodes tracked the social, and not the drug, condition: social instability upregulated the density of SNS fibres in lymph nodes and downregulated Type I interferon gene expression. Together, these results indicate that the SNS is extremely sensitive to social conditions; full understanding of the adverse effects of social instability on health should therefore incorporate measures of this health-relevant system. © 2015 The Author(s) Published by the Royal Society. All rights reserved.

  6. Effects of Phendimetrazine Treatment on Cocaine vs Food Choice and Extended-Access Cocaine Consumption in Rhesus Monkeys

    PubMed Central

    Banks, Matthew L; Blough, Bruce E; Fennell, Timothy R; Snyder, Rodney W; Negus, S Stevens

    2013-01-01

    There is currently no Food and Drug Administration-approved pharmacotherapy for cocaine addiction. Monoamine releasers such as d-amphetamine constitute one class of candidate medications, but clinical use and acceptance are hindered by their own high-abuse liability. Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine. This study determined efficacy of chronic PDM to reduce cocaine self-administration by rhesus monkeys (N=4) using a novel procedure that featured both daily assessments of cocaine vs food choice (to assess medication efficacy to reallocate behavior away from cocaine choice and toward choice of an alternative reinforcer) and 20 h/day cocaine access (to allow high-cocaine intake). Continuous 21-day treatment with ramping PDM doses (days 1–7: 0.32 mg/kg/h; days 8–21: 1.0 mg/kg/h) reduced cocaine choices, increased food choices, and nearly eliminated extended-access cocaine self-administration without affecting body weight. There was a trend for plasma PDM and PM levels to correlate with efficacy to decrease cocaine choice such that the monkey with the highest plasma PDM and PM levels also demonstrated the greatest reductions in cocaine choice. These results support further consideration of PDM as a candidate anti-cocaine addiction pharmacotherapy. Moreover, PDM may represent a novel pharmacotherapeutic approach for cocaine addiction because it may simultaneously function as both a monoamine-uptake inhibitor (via the parent drug PDM) and as a monoamine releaser (via the active metabolite PM). PMID:23893022

  7. Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.

    PubMed

    Banks, Matthew L; Blough, Bruce E; Fennell, Timothy R; Snyder, Rodney W; Negus, S Stevens

    2013-12-01

    There is currently no Food and Drug Administration-approved pharmacotherapy for cocaine addiction. Monoamine releasers such as d-amphetamine constitute one class of candidate medications, but clinical use and acceptance are hindered by their own high-abuse liability. Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine. This study determined efficacy of chronic PDM to reduce cocaine self-administration by rhesus monkeys (N=4) using a novel procedure that featured both daily assessments of cocaine vs food choice (to assess medication efficacy to reallocate behavior away from cocaine choice and toward choice of an alternative reinforcer) and 20 h/day cocaine access (to allow high-cocaine intake). Continuous 21-day treatment with ramping PDM doses (days 1-7: 0.32 mg/kg/h; days 8-21: 1.0 mg/kg/h) reduced cocaine choices, increased food choices, and nearly eliminated extended-access cocaine self-administration without affecting body weight. There was a trend for plasma PDM and PM levels to correlate with efficacy to decrease cocaine choice such that the monkey with the highest plasma PDM and PM levels also demonstrated the greatest reductions in cocaine choice. These results support further consideration of PDM as a candidate anti-cocaine addiction pharmacotherapy. Moreover, PDM may represent a novel pharmacotherapeutic approach for cocaine addiction because it may simultaneously function as both a monoamine-uptake inhibitor (via the parent drug PDM) and as a monoamine releaser (via the active metabolite PM).

  8. A freely-moving monkey treadmill model.

    PubMed

    Foster, Justin D; Nuyujukian, Paul; Freifeld, Oren; Gao, Hua; Walker, Ross; I Ryu, Stephen; H Meng, Teresa; Murmann, Boris; J Black, Michael; Shenoy, Krishna V

    2014-08-01

    Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic motor neuroscience and for the successful

  9. A freely-moving monkey treadmill model

    NASA Astrophysics Data System (ADS)

    Foster, Justin D.; Nuyujukian, Paul; Freifeld, Oren; Gao, Hua; Walker, Ross; Ryu, Stephen I.; Meng, Teresa H.; Murmann, Boris; Black, Michael J.; Shenoy, Krishna V.

    2014-08-01

    Objective. Motor neuroscience and brain-machine interface (BMI) design is based on examining how the brain controls voluntary movement, typically by recording neural activity and behavior from animal models. Recording technologies used with these animal models have traditionally limited the range of behaviors that can be studied, and thus the generality of science and engineering research. We aim to design a freely-moving animal model using neural and behavioral recording technologies that do not constrain movement. Approach. We have established a freely-moving rhesus monkey model employing technology that transmits neural activity from an intracortical array using a head-mounted device and records behavior through computer vision using markerless motion capture. We demonstrate the flexibility and utility of this new monkey model, including the first recordings from motor cortex while rhesus monkeys walk quadrupedally on a treadmill. Main results. Using this monkey model, we show that multi-unit threshold-crossing neural activity encodes the phase of walking and that the average firing rate of the threshold crossings covaries with the speed of individual steps. On a population level, we find that neural state-space trajectories of walking at different speeds have similar rotational dynamics in some dimensions that evolve at the step rate of walking, yet robustly separate by speed in other state-space dimensions. Significance. Freely-moving animal models may allow neuroscientists to examine a wider range of behaviors and can provide a flexible experimental paradigm for examining the neural mechanisms that underlie movement generation across behaviors and environments. For BMIs, freely-moving animal models have the potential to aid prosthetic design by examining how neural encoding changes with posture, environment and other real-world context changes. Understanding this new realm of behavior in more naturalistic settings is essential for overall progress of basic

  10. Dietary variety is associated with larger meals in female rhesus monkeys.

    PubMed

    Moore, Carla J; Michopoulos, Vasiliki; Johnson, Zachary P; Toufexis, Donna; Wilson, Mark E

    2013-07-02

    The complex, interacting influences on eating behavior and energy expenditure prevent elucidation of the causal role of any single factor in the current obesity epidemic. However, greater variety in the food supply, particularly in the form of highly palatable, energy-dense foods, has likely made a contribution. This study was undertaken to test the hypothesis that greater dietary variety is associated with greater caloric intake within individual meals consumed by free-feeding, socially-housed female rhesus monkeys. Meal patterns were assessed during two, two-week dietary phases. One phase consisted of a choice between a standard chow diet and a highly palatable diet (HPD). The other phase consisted of access to the chow only. Food intake for each subject was recorded continuously using previously validated, automated feeders, and a meal was defined based on a minimum kilocalorie requirement and a minimum inter-meal interval. During the choice condition, animals electively consumed mixed meals that incorporated both diets as well as other meals that consisted exclusively of a single diet - chow-only or HPD-only. Animals consumed the most calories per meal when the meal was comprised of both the chow and HPD, which differed in caloric density, flavor, and texture. Interestingly, however, there was no significant difference in the amount of calories consumed as HPD-only meals in the choice condition compared to meals in the chow-only, no choice condition, suggesting consumption of a single food during a meal, regardless of palatability, provides a constant sensory experience that may lead to more rapid habituation and subsequent meal cessation. Additionally, during the dietary choice condition, animals consumed fewer calories in the form of chow-only meals. Thus, the present results suggest that limiting dietary variety, regardless of palatability, may be a useful strategy for weight loss in overweight and obese individuals by reducing caloric intake within

  11. Do monkeys choose to choose?

    PubMed

    Perdue, Bonnie M; Evans, Theodore A; Washburn, David A; Rumbaugh, Duane M; Beran, Michael J

    2014-06-01

    Both empirical and anecdotal evidence supports the idea that choice is preferred by humans. Previous research has demonstrated that this preference extends to nonhuman animals, but it remains largely unknown whether animals will actively seek out or prefer opportunities to choose. Here we explored the issue of whether capuchin and rhesus monkeys choose to choose. We used a modified version of the SELECT task-a computer program in which monkeys can choose the order of completion of various psychomotor and cognitive tasks. In the present experiments, each trial began with a choice between two icons, one of which allowed the monkey to select the order of task completion, and the other of which led to the assignment of a task order by the computer. In either case, subjects still had to complete the same number of tasks and the same number of task trials. The tasks were relatively easy, and the monkeys responded correctly on most trials. Thus, global reinforcement rates were approximately equated across conditions. The only difference was whether the monkey chose the task order or it was assigned, thus isolating the act of choosing. Given sufficient experience with the task icons, all monkeys showed a significant preference for choice when the alternative was a randomly assigned order of tasks. To a lesser extent, some of the monkeys maintained a preference for choice over a preferred, but computer-assigned, task order that was yoked to their own previous choice selection. The results indicated that monkeys prefer to choose when all other aspects of the task are equated.

  12. The relationship between reinforcing effects and in vitro effects of D1 agonists in monkeys.

    PubMed

    Weed, M R; Paul, I A; Dwoskin, L P; Moore, S E; Woolverton, W L

    1997-10-01

    The reinforcing effects of many psychomotor stimulants have been related to increased dopaminergic neurotransmission and stimulation of central nervous system (CNS) dopamine (DA) receptors. Consistent with this notion, some drugs that directly stimulate DA receptors have been found to function as positive reinforcers. The present experiments were designed to examine why some, but not all, D1 receptor agonists can function as reinforcers in rhesus monkeys by comparing behavioral and CNS in vitro measures of potency and efficacy. Seven rhesus monkeys were allowed to self-administer cocaine under a progressive-ratio (PR) schedule until stable responding was established. Various doses of D1 agonists, previously reported to function as positive reinforcers, were then made available for self-administration. Stimulation of cAMP production in rhesus and rat striatal tissue was studied for these compounds and for D1 agonists previously reported not to function as positive reinforcers in monkeys (SKF 38393, SKF 77434 and S(-)-6-BrAPB). Blockade of DA uptake in rat striata was also examined for all compounds. SKF 81297, SKF 82958 and R(+)-6-BrAPB maintained responding under the PR schedule and did not differ significantly in efficacy as positive reinforcers; SKF 81297 was less potent than the other two agonists. SKF 81297, SKF 82958 and R(+)-6-BrAPB stimulated higher levels of cAMP production in rhesus striata than did SKF 38393, SKF 77434 and S(-)-6-BrAPB. In contrast, all compounds blocked DA uptake. Thus, reinforcing efficacy among D1 agonists increases with efficacy in stimulating D1 receptors.

  13. Effects of Long-Wavelength Lighting on Refractive Development in Infant Rhesus Monkeys

    PubMed Central

    Smith, Earl L.; Hung, Li-Fang; Arumugam, Baskar; Holden, Brien A.; Neitz, Maureen; Neitz, Jay

    2015-01-01

    Purpose Differences in the spectral composition of lighting between indoor and outdoor scenes may contribute to the higher prevalence of myopia in children who spend low amounts of time outdoors. Our goal was to determine whether environments dominated by long-wavelength light promote the development of myopia. Methods Beginning at 25 ± 2 days of age, infant monkeys were reared with long-wavelength-pass (red) filters in front of one (MRL, n = 6) or both eyes (BRL, n = 7). The filters were worn continuously until 146 ± 7 days of age. Refractive development, corneal power, and vitreous chamber depth were assessed by retinoscopy, keratometry, and ultrasonography, respectively. Control data were obtained from 6 monkeys reared with binocular neutral density (ND) filters and 33 normal monkeys reared with unrestricted vision under typical indoor lighting. Results At the end of the filter-rearing period, the median refractive error for the BRL monkeys (+4.25 diopters [D]) was significantly more hyperopic than that for the ND (+2.22 D; P = 0.003) and normal monkeys (+2.38 D; P = 0.0001). Similarly, the MRL monkeys exhibited hyperopic anisometropias that were larger than those in normal monkeys (+1.70 ± 1.55 vs. −0.013 ± 0.33 D, P < 0.0001). The relative hyperopia in the treated eyes was associated with shorter vitreous chambers. Following filter removal, the filter-reared monkeys recovered from the induced hyperopic errors. Conclusions The observed hyperopic shifts indicate that emmetropization does not necessarily target the focal plane that maximizes luminance contrast and that reducing potential chromatic cues can interfere with emmetropization. There was no evidence that environments dominated by long wavelengths necessarily promote myopia development. PMID:26447984

  14. RESPONSE LATENCIES OF NORMAL AND FOCAL-HEAD IRRADIATED MONKEYS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    McDowell, A.A.; Brown, W.L.

    1963-12-01

    This study was designed to determine whether focal-head irradiated rhesus monkeys differ from normal monkeys in a manner analogous to that previously found in whole-body irradiated monkeys with respect to response latencies under both familiar and novel stimulus conditions. Five control and four focal-head irradiated rhesus monkeys with nearly identical training histories were used; the latter were survivors of a focal-head irradiation study conducted four years earlier. They had received 3000 r x radiation to the inferior parietal lobule and posterior aspect of the temporal lobe of the brain, and 30 days later the same dosage to the same areamore » of the brain. The testing was conducted in a modified version of the Wisconsin General Test Apparatus, with 24 trials per day for two days, on response latency to a single food-rewarded wooden block placed randomly over either of the two extreme food-well positions. Then, 24 trials were conducted per day for two days on response latency to either the same food-rewarded wooden block or to a novel nonrewarded wooden block presented simultaneously. On the single-block condition, median response latencies of the two groups were comparable and the groups improved in a similar manner with practice. Optimal performance latencies were also comparable for the two groups. When the novel nonrewarded stimulus block was introduced, both groups manifested comparable disruption of median response latencies, but disruption of optimal response latencies was shown only by the focalhead irradiated group. The findings show that monkeys with previous focal-head irradiation of the posterior association areas, unlike relatively high-dose whole-body irradiated monkeys, manifest median response latencies comparable to those of controls. These data indicate the lasting effects of focal-head irradiation with x rays, and suggest that the sites of permanent damage for monkeys given sublethal whole-body radiation exposure differ from the sites

  15. Effects of a Serotonin 2C Agonist and a 2A Antagonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys.

    PubMed

    Perez Diaz, Maylen; Andersen, Monica L; Rice, Kenner C; Howell, Leonard L

    2017-06-01

    Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under well-controlled conditions in laboratory animals. Thus, we examined the effects of a 5-HT 2C receptor agonist, WAY163909, and a 5-HT 2A receptor antagonist, M100907, given alone and in combination, on actigraphy-based sleep parameters disrupted by methamphetamine self-administration in non-human primates. Adult male/female rhesus monkeys self-administered methamphetamine (0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week). Nighttime activity was evaluated using Actiwatch monitors. WAY163909 (0.1, 0.3, and 1.0 mg/kg), M100907 (0.03, 0.1, and 0.3 mg/kg), and a combination (0.1 mg/kg M100+0.3 mg/kg WAY) were administered i.m. before lights-out. Each dose was given for five consecutive days during which self-administration took place in the morning. Both drugs improved activity-based sleep measures disrupted by methamphetamine by decreasing sleep latency and increasing sleep efficiency compared with vehicle. By combining these drugs, their individual effects were significantly enhanced. Agonists at the 5-HT 2C receptor and antagonists at the 5-HT 2A receptor show promise as potential treatments for the sleep-disrupting effects of stimulants when used alone and in combination. Combining subthreshold doses of WAY and M100 produced significant improvements in nighttime activity measures while avoiding the general motor-decreasing effects of the high dose of WAY.

  16. Effects of a Serotonin 2C Agonist and a 2A Antagonist on Actigraphy-Based Sleep Parameters Disrupted by Methamphetamine Self-Administration in Rhesus Monkeys

    PubMed Central

    Perez Diaz, Maylen; Andersen, Monica L; Rice, Kenner C; Howell, Leonard L

    2017-01-01

    Sleep disorders and substance abuse are highly comorbid and we have previously shown that methamphetamine self-administration significantly disrupts activity-based sleep parameters in rhesus monkeys. To the best of our knowledge, no study has evaluated the effectiveness of any pharmacological intervention to attenuate the effects of methamphetamine on nighttime activity under well-controlled conditions in laboratory animals. Thus, we examined the effects of a 5-HT2C receptor agonist, WAY163909, and a 5-HT2A receptor antagonist, M100907, given alone and in combination, on actigraphy-based sleep parameters disrupted by methamphetamine self-administration in non-human primates. Adult male/female rhesus monkeys self-administered methamphetamine (0.03 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement (60-min sessions once a day, 5 days per week). Nighttime activity was evaluated using Actiwatch monitors. WAY163909 (0.1, 0.3, and 1.0 mg/kg), M100907 (0.03, 0.1, and 0.3 mg/kg), and a combination (0.1 mg/kg M100+0.3 mg/kg WAY) were administered i.m. before lights-out. Each dose was given for five consecutive days during which self-administration took place in the morning. Both drugs improved activity-based sleep measures disrupted by methamphetamine by decreasing sleep latency and increasing sleep efficiency compared with vehicle. By combining these drugs, their individual effects were significantly enhanced. Agonists at the 5-HT2C receptor and antagonists at the 5-HT2A receptor show promise as potential treatments for the sleep-disrupting effects of stimulants when used alone and in combination. Combining subthreshold doses of WAY and M100 produced significant improvements in nighttime activity measures while avoiding the general motor-decreasing effects of the high dose of WAY. PMID:27986974

  17. Dynamic Response-by-Response Models of Matching Behavior in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Lau, Brian; Glimcher, Paul W.

    2005-01-01

    We studied the choice behavior of 2 monkeys in a discrete-trial task with reinforcement contingencies similar to those Herrnstein (1961) used when he described the matching law. In each session, the monkeys experienced blocks of discrete trials at different relative-reinforcer frequencies or magnitudes with unsignalled transitions between the…

  18. Monkey Visual Short-Term Memory Directly Compared to Humans

    PubMed Central

    Elmore, L. Caitlin; Wright, Anthony A.

    2015-01-01

    Two adult rhesus monkeys were trained to detect which item in an array of memory items had changed using the same stimuli, viewing times, and delays as used with humans. Although the monkeys were extensively trained, they were less accurate than humans with the same array sizes (2, 4, & 6 items), with both stimulus types (colored squares, clip art), and showed calculated memory capacities of about one item (or less). Nevertheless, the memory results from both monkeys and humans for both stimulus types were well characterized by the inverse power-law of display size. This characterization provides a simple and straightforward summary of a fundamental process of visual short-term memory (how VSTM declines with memory load) that emphasizes species similarities based upon similar functional relationships. By more closely matching of monkey testing parameters to those of humans, the similar functional relationships strengthen the evidence suggesting similar processes underlying monkey and human VSTM. PMID:25706544

  19. Head Rotation Detection in Marmoset Monkeys

    NASA Astrophysics Data System (ADS)

    Simhadri, Sravanthi

    Head movement is known to have the benefit of improving the accuracy of sound localization for humans and animals. Marmoset is a small bodied New World monkey species and it has become an emerging model for studying the auditory functions. This thesis aims to detect the horizontal and vertical rotation of head movement in marmoset monkeys. Experiments were conducted in a sound-attenuated acoustic chamber. Head movement of marmoset monkey was studied under various auditory and visual stimulation conditions. With increasing complexity, these conditions are (1) idle, (2) sound-alone, (3) sound and visual signals, and (4) alert signal by opening and closing of the chamber door. All of these conditions were tested with either house light on or off. Infra-red camera with a frame rate of 90 Hz was used to capture of the head movement of monkeys. To assist the signal detection, two circular markers were attached to the top of monkey head. The data analysis used an image-based marker detection scheme. Images were processed using the Computation Vision Toolbox in Matlab. The markers and their positions were detected using blob detection techniques. Based on the frame-by-frame information of marker positions, the angular position, velocity and acceleration were extracted in horizontal and vertical planes. Adaptive Otsu Thresholding, Kalman filtering and bound setting for marker properties were used to overcome a number of challenges encountered during this analysis, such as finding image segmentation threshold, continuously tracking markers during large head movement, and false alarm detection. The results show that the blob detection method together with Kalman filtering yielded better performances than other image based techniques like optical flow and SURF features .The median of the maximal head turn in the horizontal plane was in the range of 20 to 70 degrees and the median of the maximal velocity in horizontal plane was in the range of a few hundreds of degrees per

  20. Chemical composition of axillary odorants reflects social and individual attributes in rhesus macaques.

    PubMed

    Weiß, Brigitte M; Kücklich, Marlen; Thomsen, Ruth; Henkel, Stefanie; Jänig, Susann; Kulik, Lars; Birkemeyer, Claudia; Widdig, Anja

    2018-01-01

    Scents play an important role in the life of most terrestrial mammals and may transmit valuable information about conspecifics. Olfaction was long considered of low importance in Old World monkeys due to their relative reduction of olfactory structures and low incidence of scent-marking behavior but has been increasingly recognized for mediating social relationships in recent years. Yet, studies investigating the composition of their chemical cues remain scarce. In the present study, we analyzed the potential information content of chemicals present on the skin of rhesus macaques ( Macaca mulatta ). We collected axillary secretions from 60 animals of the semifree-ranging population on Cayo Santiago (Puerto Rico, USA) with precleaned cotton swabs from which the secretions were subsequently extracted and analyzed by gas chromatography-mass spectrometry. Rhesus macaque axillary odorants varied in their overall similarity and composition. This variation was attributable to differences in sex, group membership, and kinship and further appeared to reflect age and rank in parts of our sample. The compounds most strongly associated with this variation primarily comprised larger molecular weight aldehydes and steroids. Such compounds are considered to be perceivable by the primate olfactory system through close-range interactions or through breakdown into smaller molecules by bacterial fermentation. Overall, our results provide additional evidence that odors of Old World monkeys reflect a wealth of potential information about their carrier, which provides the basis for chemical communication via body odors; however, its use by conspecifics needs to be confirmed in bioassays. One prerequisite for olfactory communication is the presence of systematic variation in animal odors that is related to attributes such as age, sex, or kinship. The composition of odors has been examined in numerous mammals but, with the exception of humans, remains poorly understood in Old World

  1. The pathology of innactivation in monkeys.

    NASA Technical Reports Server (NTRS)

    Bourne, G. H.; Golarz De Bourne, M. N.; Mcclure, H.; Keeling, M.

    1973-01-01

    Progress report on a long-term experiment using rhesus monkeys and designed to study the effects of isolation up to one year, as well as the effects of bed rest simulated by immobilization in a plaster cast for six months. The investigation includes histopathological and histochemical studies of these effects on various internal organs and tissues, and some of the preliminary results of these studies are presented and discussed.

  2. Funduscopic alterations in the rhesus monkey induced by exposure to heavy ions /0+8/ 250 MeV/nucleon

    NASA Technical Reports Server (NTRS)

    Beckman, F. N.; Bonney, C. H.; Hunter, D. M.

    1974-01-01

    A heavy-ion, high-energy beam has been extracted from the Lawrence Radiation Laboratory Bevatron, making controlled exposure of biological systems feasible, and a series of experiments have been undertaken to determine the possible deleterious effects of such irradiation upon the primate retina. The left eyes of 54 rhesus monkeys have been exposed to accelerated 0+8 (250 MeV/nucleon). Beam flux ranged from 1.3 x 10 to the 7th particles/ sq cm (171 rads) to 5.9 x 10 to the 8th particles/sq cm (7740 rads). Fundus photography was performed immediately prior to and immediately following exposure, at 24 to 48 hours postexposure and at 1, 2, and 5 weeks postexposure. Punctate hemorrhages of the retina were visible at 1.3 x 10 to the 7th particles/sq cm (171 rads), the lowest exposure level utilized in this study. Acute radiation retinopathy, consisting of geographic retinal hemorrhage and ischemic necrosis of the retina, was not seen until total flux reached 7.7 x 10 to the 7th particles/sq cm (1000 rads).

  3. Development of breeding populations of rhesus macaques (Macaca mulatta) that are specific pathogen-free for rhesus cytomegalovirus.

    PubMed

    Barry, Peter A; Strelow, Lisa

    2008-02-01

    Development of breeding colonies of rhesus macaques (Macaca mulatta) that are specific pathogen-free (SPF) for rhesus cytomegalovirus (RhCMV) is relatively straightforward and requires few modifications from current SPF programs. Infants separated from the dam at or within a few days of birth and cohoused with similarly treated animals remain RhCMV seronegative indefinitely, provided they are never directly or indirectly exposed to a RhCMV-infected monkey. By systematically cohousing seronegative animals into larger social cohorts, breeding populations of animals SPF for RhCMV can be established. The additional costs involved in expanding the current definition of SPF status to include RhCMV are incremental compared with the money already being spent on existing SPF efforts. Moreover, the large increase in research opportunities available for RhCMV-free animals arguably would far exceed the development costs. Potential new areas of research and further expansion of existing research efforts involving these newly defined SPF animals would have direct implications for improvements in human health.

  4. Spontaneous expression of mirror self-recognition in monkeys after learning precise visual-proprioceptive association for mirror images

    PubMed Central

    Chang, Liangtang; Zhang, Shikun; Poo, Mu-ming; Gong, Neng

    2017-01-01

    Mirror self-recognition (MSR) is generally considered to be an intrinsic cognitive ability found only in humans and a few species of great apes. Rhesus monkeys do not spontaneously show MSR, but they have the ability to use a mirror as an instrument to find hidden objects. The mechanism underlying the transition from simple mirror use to MSR remains unclear. Here we show that rhesus monkeys could show MSR after learning precise visual-proprioceptive association for mirror images. We trained head-fixed monkeys on a chair in front of a mirror to touch with spatiotemporal precision a laser pointer light spot on an adjacent board that could only be seen in the mirror. After several weeks of training, when the same laser pointer light was projected to the monkey's face, a location not used in training, all three trained monkeys successfully touched the face area marked by the light spot in front of a mirror. All trained monkeys passed the standard face mark test for MSR both on the monkey chair and in their home cage. Importantly, distinct from untrained control monkeys, the trained monkeys showed typical mirror-induced self-directed behaviors in their home cage, such as using the mirror to explore normally unseen body parts. Thus, bodily self-consciousness may be a cognitive ability present in many more species than previously thought, and acquisition of precise visual-proprioceptive association for the images in the mirror is critical for revealing the MSR ability of the animal. PMID:28193875

  5. Bilateral neurotoxic amygdala lesions in rhesus monkeys (Macaca mulatta): Consistent pattern of behavior across different social contexts

    PubMed Central

    Machado, Christopher J.; Emery, Nathan J.; Capitanio, John P.; Mason, William A.; Mendoza, Sally P.; Amaral, David G.

    2010-01-01

    Although the amygdala has been repeatedly implicated in normal primate social behavior, great variability exists in the specific social and nonsocial behavioral changes observed after bilateral amygdala lesions in nonhuman primates. One plausible explanation pertains to differences in social context. To investigate this idea, we measured the social behavior of amygdala-lesioned and unoperated rhesus monkeys (Macaca mulatta) in two contexts. Animals interacted in four-member social groups over 32 test days. These animals were previously assessed in pairs (Emery et al., 2001), and were, therefore, familiar with each other at the beginning of this study. Across the two contexts, amygdala lesions produced a highly consistent pattern of social behavior. Operated animals engaged in more affiliative social interactions with control group partners than did control animals. In the course of their interactions, amygdala-lesioned animals also displayed an earlier decrease in nervous and fearful personality qualities than controls. The increased exploration and sexual behavior recorded for amygdala-lesioned animals in pairs was not found in the four-member groups. We conclude that the amygdala contributes to social inhibition and this function transcends various social contexts. PMID:18410164

  6. Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems

    NASA Technical Reports Server (NTRS)

    Chen, Silvia S.; Revoltella, Roberto P.; Papini, Sandra; Michelini, Monica; Fitzgerald, Wendy; Zimmerberg, Joshua; Margolis, Leonid

    2003-01-01

    In the course of normal embryogenesis, embryonic stem (ES) cells differentiate along different lineages in the context of complex three-dimensional (3D) tissue structures. In order to study this phenomenon in vitro under controlled conditions, 3D culture systems are necessary. Here, we studied in vitro differentiation of rhesus monkey ES cells in 3D collagen matrixes (collagen gels and porous collagen sponges). Differentiation of ES cells in these 3D systems was different from that in monolayers. ES cells differentiated in collagen matrixes into neural, epithelial, and endothelial lineages. The abilities of ES cells to form various structures in two chemically similar but topologically different matrixes were different. In particular, in collagen gels ES cells formed gland-like circular structures, whereas in collagen sponges ES cells were scattered through the matrix or formed aggregates. Soluble factors produced by feeder cells or added to the culture medium facilitated ES cell differentiation into particular lineages. Coculture with fibroblasts in collagen gel facilitated ES cell differentiation into cells of a neural lineage expressing nestin, neural cell adhesion molecule, and class III beta-tubulin. In collagen sponges, keratinocytes facilitated ES cell differentiation into cells of an endothelial lineage expressing factor VIII. Exogenous granulocyte-macrophage colony-stimulating factor further enhanced endothelial differentiation. Thus, both soluble factors and the type of extracellular matrix seem to be critical in directing differentiation of ES cells and the formation of tissue-like structures. Three-dimensional culture systems are a valuable tool for studying the mechanisms of these phenomena.

  7. Working and waiting for better rewards: self-control in two monkey species (Cebus apella and Macaca mulatta).

    PubMed

    Evans, Theodore A; Perdue, Bonnie M; Parrish, Audrey E; Beran, Michael J

    2014-03-01

    Self-control is typically defined as choosing a greater, delayed reward over a lesser, more immediate reward. However, in nature, there are other costs besides delay associated with obtaining the greatest outcome including increased effort, potential punishment, and low probability of reward. Effort is an interesting case because it sometimes impairs self-control, by acting as an additional cost, and at other times facilitates self-control, by distracting one from impulsive options. Additionally, different species may perform differently in effortful self-control tasks, based on their natural ecology. To gain insight into these aspects of self-control behavior, we examined capuchin monkeys' and rhesus monkeys' self-control in separate working and waiting choice tasks. We hypothesized that capuchins would show greater self-control in the working task, given their naturally higher activity level, whereas rhesus would perform similarly in both tasks. Rhesus performed as predicted, whereas contrary to our hypothesis, capuchins exhibited lesser performance in the working task. Nonetheless, these results may still stem from inherent species differences interacting with details of the methodology. Capuchins, being highly energetic and social monkeys, may have divided their energy and attention between the working task and other elements of the test environment such as visible group mates or manipulanda. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Ambiguity Aversion in Rhesus Macaques

    PubMed Central

    Hayden, Benjamin Y.; Heilbronner, Sarah R.; Platt, Michael L.

    2010-01-01

    People generally prefer risky options, which have fully specified outcome probabilities, to ambiguous options, which have unspecified probabilities. This preference, formalized in economics, is strong enough that people will reliably prefer a risky option to an ambiguous option with a greater expected value. Explanations for ambiguity aversion often invoke uniquely human faculties like language, self-justification, or a desire to avoid public embarrassment. Challenging these ideas, here we demonstrate that a preference for unambiguous options is shared with rhesus macaques. We trained four monkeys to choose between pairs of options that both offered explicitly cued probabilities of large and small juice outcomes. We then introduced occasional trials where one of the options was obscured and examined their resulting preferences; we ran humans in a parallel experiment on a nearly identical task. We found that monkeys reliably preferred risky options to ambiguous ones, even when this bias was costly, closely matching the behavior of humans in the analogous task. Notably, ambiguity aversion varied parametrically with the extent of ambiguity. As expected, ambiguity aversion gradually declined as monkeys learned the underlying probability distribution of rewards. These data indicate that ambiguity aversion reflects fundamental cognitive biases shared with other animals rather than uniquely human factors guiding decisions. PMID:20922060

  9. Repeat sample intraocular pressure variance in induced and naturally ocular hypertensive monkeys.

    PubMed

    Dawson, William W; Dawson, Judyth C; Hope, George M; Brooks, Dennis E; Percicot, Christine L

    2005-12-01

    To compare repeat-sample means variance of laser induced ocular hypertension (OH) in rhesus monkeys with the repeat-sample mean variance of natural OH in age-range matched monkeys of similar and dissimilar pedigrees. Multiple monocular, retrospective, intraocular pressure (IOP) measures were recorded repeatedly during a short sampling interval (SSI, 1-5 months) and a long sampling interval (LSI, 6-36 months). There were 5-13 eyes in each SSI and LSI subgroup. Each interval contained subgroups from the Florida with natural hypertension (NHT), induced hypertension (IHT1) Florida monkeys, unrelated (Strasbourg, France) induced hypertensives (IHT2), and Florida age-range matched controls (C). Repeat-sample individual variance means and related IOPs were analyzed by a parametric analysis of variance (ANOV) and results compared to non-parametric Kruskal-Wallis ANOV. As designed, all group intraocular pressure distributions were significantly different (P < or = 0.009) except for the two (Florida/Strasbourg) induced OH groups. A parametric 2 x 4 design ANOV for mean variance showed large significant effects due to treatment group and sampling interval. Similar results were produced by the nonparametric ANOV. Induced OH sample variance (LSI) was 43x the natural OH sample variance-mean. The same relationship for the SSI was 12x. Laser induced ocular hypertension in rhesus monkeys produces large IOP repeat-sample variance mean results compared to controls and natural OH.

  10. Maternal antibodies against tetanus toxoid do not inhibit potency of antibody responses to autologous antigen in newborn rhesus monkeys.

    PubMed

    Veazey, Ronald S; Lu, Yingjie; Xu, Huanbin; Ziani, Widade; Doyle-Meyers, Lara A; Ratterree, Marion S; Wang, Xiaolei

    2018-02-01

    Our previous study suggested newborns have competent immune systems with the potential to respond to foreign antigens and vaccines. In this study, we examined infant immune responses to tetanus toxoid (TT) vaccination in the presence of maternal antibody to TT. We examined changes in plasma levels of tetanus toxoid-specific IgG1 (anti-TT IgG1) in a total of eight infant rhesus macaques from birth through 6 months of age using a commercial Monkey Anti-TT IgG1 ELISA kit. A significant correlation between anti-TT IgG1 levels in vaccinated dams and their paired newborn infants was detected in control (non-vaccinated) infants as previously reported. Maternal anti-TT IgG1 levels declined rapidly within 1 month of birth in non-vaccinated infants (n=4). In four infants vaccinated with TT at birth, we found two had rapid and robust antibody responses to vaccination. Interestingly, the other two first showed declining TT antibody levels for 2 weeks followed by increasing levels without additional vaccine boosts, indicating all four had good antibody responses to primary TT vaccination at birth, despite the presence of high levels of maternal antibodies to TT in all four infants. Our data indicate that newborn macaques have competent immune systems that are capable of generating their own primary antibody responses to vaccination, at least to tetanus antigens. Maternal antibodies thus do not significantly impair antibody response to the vaccination, even when received on the day of birth in infant rhesus macaques. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Cocaine-like discriminative stimulus effects of "norepinephrine-preferring" monoamine releasers: time course and interaction studies in rhesus monkeys.

    PubMed

    Kohut, Stephen J; Jacobs, David S; Rothman, Richard B; Partilla, John S; Bergman, Jack; Blough, Bruce E

    2017-12-01

    The therapeutic potential of monoamine releasers with prominent dopaminergic effects is hindered by their high abuse liability. The present study examined the effects of several novel "norepinephrine (NE)-preferring" monoamine releasers relative to non-selective monoamine releasers, d-amphetamine and d-methamphetamine, in rhesus monkeys trained to discriminate cocaine. NE-preferring releasers were approximately 13-fold more potent for NE compared to dopamine release and ranged in potency for serotonin release (PAL-329 < l-methamphetamine < PAL-169). Adult rhesus macaques were trained to discriminate 0.4 mg/kg, IM cocaine on a 30-response fixed ratio schedule of food reinforcement. Substitution studies determined the extent to which test drugs produced cocaine-like discriminative stimulus effects and their time course. Drug interaction studies determined whether pretreatment with test drugs altered the discriminable effects of cocaine. Results show that cocaine, d-amphetamine, and d-methamphetamine dose-dependently substituted for cocaine with similar potencies. Among the "NE-preferring" releasers, PAL-329 and l-methamphetamine also dose-dependently substituted for cocaine but differed in potency. PAL-169 failed to substitute for cocaine up to a dose that disrupted responding. When administered prior to cocaine, only d-amphetamine and PAL-329 significantly shifted the cocaine dose-effect function leftward indicating enhancement of cocaine's discriminative stimulus effects. These data suggest that greater potency for NE relative to dopamine release (up to 13-fold) does not interfere with the ability of a monoamine releaser to produce cocaine-like discriminative effects but that increased serotonin release may have an inhibitory effect. Further characterization of these and other "NE-preferring" monoamine releasers should provide insight into their potential for the management of cocaine addiction.

  12. Using infective mosquitoes to challenge monkeys with Plasmodium knowlesi in malaria vaccine studies.

    PubMed

    Murphy, Jittawadee R; Weiss, Walter R; Fryauff, David; Dowler, Megan; Savransky, Tatyana; Stoyanov, Cristina; Muratova, Olga; Lambert, Lynn; Orr-Gonzalez, Sachy; Zeleski, Katie Lynn; Hinderer, Jessica; Fay, Michael P; Joshi, Gyan; Gwadz, Robert W; Richie, Thomas L; Villasante, Eileen Franke; Richardson, Jason H; Duffy, Patrick E; Chen, Jingyang

    2014-06-03

    When rhesus monkeys (Macaca mulatta) are used to test malaria vaccines, animals are often challenged by the intravenous injection of sporozoites. However, natural exposure to malaria comes via mosquito bite, and antibodies can neutralize sporozoites as they traverse the skin. Thus, intravenous injection may not fairly assess humoral immunity from anti-sporozoite malaria vaccines. To better assess malaria vaccines in rhesus, a method to challenge large numbers of monkeys by mosquito bite was developed. Several species and strains of mosquitoes were tested for their ability to produce Plasmodium knowlesi sporozoites. Donor monkey parasitaemia effects on oocyst and sporozoite numbers and mosquito mortality were documented. Methylparaben added to mosquito feed was tested to improve mosquito survival. To determine the number of bites needed to infect a monkey, animals were exposed to various numbers of P. knowlesi-infected mosquitoes. Finally, P. knowlesi-infected mosquitoes were used to challenge 17 monkeys in a malaria vaccine trial, and the effect of number of infectious bites on monkey parasitaemia was documented. Anopheles dirus, Anopheles crascens, and Anopheles dirus X (a cross between the two species) produced large numbers of P. knowlesi sporozoites. Mosquito survival to day 14, when sporozoites fill the salivary glands, averaged only 32% when donor monkeys had a parasitaemia above 2%. However, when donor monkey parasitaemia was below 2%, mosquitoes survived twice as well and contained ample sporozoites in their salivary glands. Adding methylparaben to sugar solutions did not improve survival of infected mosquitoes. Plasmodium knowlesi was very infectious, with all monkeys developing blood stage infections if one or more infected mosquitoes successfully fed. There was also a dose-response, with monkeys that received higher numbers of infected mosquito bites developing malaria sooner. Anopheles dirus, An. crascens and a cross between these two species all were

  13. Interaction between behavioral and pharmacological treatment strategies to decrease cocaine choice in rhesus monkeys.

    PubMed

    Banks, Matthew L; Blough, Bruce E; Negus, S Stevens

    2013-02-01

    Behavioral and pharmacotherapeutic approaches constitute two prominent strategies for treating cocaine dependence. This study investigated interactions between behavioral and pharmacological strategies in a preclinical model of cocaine vs food choice. Six rhesus monkeys, implanted with a chronic indwelling double-lumen venous catheter, initially responded under a concurrent schedule of food delivery (1-g pellets, fixed-ratio (FR) 100 schedule) and cocaine injections (0-0.1 mg/kg/injection, FR 10 schedule) during continuous 7-day treatment periods with saline or the agonist medication phenmetrazine (0.032-0.1 mg/kg/h). Subsequently, the FR response requirement for cocaine or food was varied (food, FR 100; cocaine, FR 1-100; cocaine, FR 10; food, FR 10-300), and effects of phenmetrazine on cocaine vs food choice were redetermined. Decreases in the cocaine FR or increases in the food FR resulted in leftward shifts in the cocaine choice dose-effect curve, whereas increases in the cocaine FR or decreases in the food FR resulted in rightward shifts in the cocaine choice dose-effect curve. The efficacy of phenmetrazine to decrease cocaine choice varied systematically as a function of the prevailing response requirements, such that phenmetrazine efficacy was greatest when cocaine choice was maintained by relatively low unit cocaine doses. These results suggest that efficacy of pharmacotherapies to modulate cocaine use can be influenced by behavioral contingencies of cocaine availability. Agonist medications may be most effective under contingencies that engender choice of relatively low cocaine doses.

  14. Actigraphy-based sleep parameters during the reinstatement of methamphetamine self-administration in rhesus monkeys.

    PubMed

    Berro, Laís F; Andersen, Monica L; Tufik, Sergio; Howell, Leonard L

    2016-04-01

    The objective of this study was to investigate nighttime activity of nonhuman primates during extinction and cue- and drug-primed reinstatement of methamphetamine self-administration. Adult rhesus monkeys (Macaca mulatta; n = 5) self-administered methamphetamine (0.01 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement. Saline infusions were then substituted for methamphetamine and stimulus light (drug-conditioned stimulus presented during drug self-administration) withheld until subjects reached extinction criteria. Drug- and cue-induced reinstatement effects were evaluated after i.v. noncontingent priming injections of methamphetamine (0.03, 0.1, or 0.3 mg/kg). Activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline nighttime activity parameters) and throughout the protocol. Although methamphetamine self-administration did not significantly affect nighttime activity compared to baseline, sleeplike parameters were improved during extinction compared to self-administration maintenance. Priming injection of 0.1 mg/kg methamphetamine, but not 0.03 or 0.3 mg/kg, induced significant reinstatement effects. These behavioral responses were accompanied by nighttime outcomes, with increased sleep fragmentation and decreased sleep efficiency in the night following 0.1 mg/kg methamphetamine-induced reinstatement. In the absence of both drug and drug-paired cues (extinction conditions), nighttime activity decreased compared to self-administration maintenance. Additionally, effective reinstatement conditions impaired sleeplike measures. Our data indicate that the reintroduction of the stimulus light as a drug-paired cue increased nighttime activity. (c) 2016 APA, all rights reserved).

  15. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys.

    PubMed

    Maguire, David R; France, Charles P

    2016-04-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

  16. Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Slikker, W. Jr.; Althaus, Z.R.; Rowland, J.M.

    1982-11-01

    The late gestational age rhesus monkey was used to study the transplacental pharmacokinetics of radiolabeled triamcinolone acetonide (TAC) and cortisol. Tritiated-TAC and (/sup 14/C)cortisol were administered simultaneously via the maternal radial vein were administered simultaneously via the maternal radial vein and blood samples were serially drawn from catheters implanted in both the maternal femoral artery and fetal umbilical vein and artery. High-performance liquid chromatography of the processed blood samples revealed that from 93 to 100% of the /sup 3/H in the fetal circulation was parent TAC, whereas only 14 to 49% of the /sup 14/C was cortisol during the 40-minmore » period after dose administration. Fetal tissue samples taken at 3 hr after dose administration showed that 75 to 96% of the /sup 3/H present was TAC, whereas no cortisol was observed. TAC demonstrated dose-independent kinetics. Samples collected from the umbilical vein of the in situ placenta after fetectomy revealed that cortisol was extensively converted to cortisone by the placenta, whereas TAC was refractory to placental metabolism. This placental conversion of cortisol to cortisone and the further metabolism and conjugation of cortisol by the fetoplacental unit resulted in a fetal to maternal plasma cortisol ratio of 0.2. In contrast, the lack of placental or fetoplacental metabolism of TAC resulted in a fetal to maternal plasma TAC ratio of 0.6.« less

  17. Processing of frequency-modulated sounds in the lateral auditory belt cortex of the rhesus monkey.

    PubMed

    Tian, Biao; Rauschecker, Josef P

    2004-11-01

    Single neurons were recorded from the lateral belt areas, anterolateral (AL), mediolateral (ML), and caudolateral (CL), of nonprimary auditory cortex in 4 adult rhesus monkeys under gas anesthesia, while the neurons were stimulated with frequency-modulated (FM) sweeps. Responses to FM sweeps, measured as the firing rate of the neurons, were invariably greater than those to tone bursts. In our stimuli, frequency changed linearly from low to high frequencies (FM direction "up") or high to low frequencies ("down") at varying speeds (FM rates). Neurons were highly selective to the rate and direction of the FM sweep. Significant differences were found between the 3 lateral belt areas with regard to their FM rate preferences: whereas neurons in ML responded to the whole range of FM rates, AL neurons responded better to slower FM rates in the range of naturally occurring communication sounds. CL neurons generally responded best to fast FM rates at a speed of several hundred Hz/ms, which have the broadest frequency spectrum. These selectivities are consistent with a role of AL in the decoding of communication sounds and of CL in the localization of sounds, which works best with broader bandwidths. Together, the results support the hypothesis of parallel streams for the processing of different aspects of sounds, including auditory objects and auditory space.

  18. Metabolism of lithocholic and chenodeoxycholic acids in the squirrel monkey

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Suzuki, H.; Hamada, M.; Kato, F.

    1985-09-01

    Metabolism of lithocholic acid (LCA) and chenodeoxycholic acid (CDCA) was studied in the squirrel monkey to clarify the mechanism of the lack of toxicity of CDCA in this animal. Radioactive LCA was administered to squirrel monkeys with biliary fistula. Most radioactivity was excreted in the bile in the form of unsulfated lithocholyltaurine. The squirrel monkey thus differs from humans and chimpanzees, which efficiently sulfate LCA, and is similar to the rhesus monkey and baboon in that LCA is poorly sulfated. When labeled CDCA was orally administered to squirrel monkeys, less than 20% of the dosed radioactivity was recovered as LCAmore » and its further metabolites in feces over 3 days, indicating that bacterial metabolism of CDCA into LCA is strikingly less than in other animals and in humans. It therefore appears that LCA, known as a hepatotoxic secondary bile acid, is not accumulated in the squirrel monkey, not because of its rapid turnover through sulfation, but because of the low order of its production.« less

  19. Intra-renal arterial injection of autologous bone marrow mesenchymal stromal cells ameliorates cisplatin-induced acute kidney injury in a rhesus Macaque mulatta monkey model.

    PubMed

    Moghadasali, Reza; Azarnia, Mahnaz; Hajinasrollah, Mostafa; Arghani, Hassan; Nassiri, Seyed Mahdi; Molazem, Mohammad; Vosough, Ahmad; Mohitmafi, Soroush; Najarasl, Mostafa; Ajdari, Zahra; Yazdi, Reza Salman; Bagheri, Mohsen; Ghanaati, Hossein; Rafiei, Behrooz; Gheisari, Yousof; Baharvand, Hossein; Aghdami, Nasser

    2014-06-01

    Clinically, acute kidney injury (AKI) is a potentially devastating condition for which no specific therapy improves efficacy of the repair process. Bone marrow mesenchymal stromal cells (BM-MSCs) are proven to be beneficial for the renal repair process after AKI in different experimental rodent models, but their efficacy in large animals and humans remains unknown. This study aims to assess the effect of autologous rhesus Macaque mulatta monkey BM-MSC transplantation in cisplatin-induced AKI. We chose a model of AKI induced by intravenous administration of 5 mg/kg cisplatin. BM-MSCs were transplanted through intra-arterial injection. The animals were followed for survival, biochemistry analysis and pathology. Transplantation of 5 × 10(6) cells/kg ameliorated renal function during the first week, as shown by significantly lower serum creatinine and urea values and higher urine creatinine and urea clearance without hyponatremia, hyperkalemia, proteinuria and polyuria up to 84 d compared with the vehicle and control groups. The superparamagnetic iron oxide nanoparticle-labeled cells were found in both the glomeruli and tubules. BM-MSCs markedly accelerated Foxp3+ T-regulatory cells in response to cisplatin-induced damage, as revealed by higher numbers of Foxp3+ cells within the tubuli of these monkeys compared with cisplatin-treated monkeys in the control and vehicle groups. These data demonstrate that BM-MSCs in this unique large-animal model of cisplatin-induced AKI exhibited recovery and protective properties. Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

  20. Evaluation of a DNA Aβ42 vaccine in adult rhesus monkeys (Macaca mulatta): antibody kinetics and immune profile after intradermal immunization with full-length DNA Aβ42 trimer.

    PubMed

    Lambracht-Washington, Doris; Fu, Min; Frost, Pat; Rosenberg, Roger N

    2017-04-26

    Aggregated amyloid-β peptide 1-42 (Aβ42), derived from the cellular amyloid precursor protein, is one of the pathological hallmarks of Alzheimer's disease (AD). Although active immunization against Aβ42 peptide was successful in AD mouse models and led to removal of plaques and improved memory, a similar clinical trial in humans (Aβ42 peptide immunization with QS-21 adjuvant) was stopped in phase II, when 6% of the treated patients developed encephalitis. Currently ongoing passive immunizations with the injection of preformed monoclonal antibodies against different epitopes within the Aβ 1-42 peptide, which do not lead to activation of the immune system, have shown some effects in slowing AD pathology. Active DNA Aβ42 immunizations administered with the gene gun into the skin are noninflammatory because they activate a different T-cell population (Th2) with different cytokine responses eliciting a different humoral immune response. We present our findings in rhesus macaques that underwent the DNA Aβ42 immunization via gene gun delivery into the skin. Six rhesus monkeys received two different doses of a DNA Aβ42 trimer vaccine. The humoral immune response was analyzed from blood throughout the study, and cellular immune responses were determined in peripheral blood mononuclear cells (PBMCs) after three and six immunizations. DNA Aβ42 trimer immunization led to high titer antibody responses in the nonhuman primate (NHP) model. Antibodies generated in the rhesus monkeys following DNA Aβ42 immunization detected amyloid plaques consisting of human Aβ42 peptide in the brain of the triple-transgenic AD mouse model. T-cell responses showed no interferon (IFN)-γ- and interleukin (IL)-17-producing cells from PBMCs in Enzyme-Linked ImmunoSpot assays after three immunization time points. At six immunization time points, IFN-γ- and IL-17-producing cells were found in immunized animals as well as in control animals and were thus considered nonspecific and not due to