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Sample records for alert rhesus monkeys

  1. Changes in the horizontal vestibulo-ocular reflex of the rhesus monkey with behavioral and pharmacological alerting.

    PubMed

    Furman, J M; O'Leary, D P; Wolfe, J W

    1981-02-16

    It is well known that eye movements are influenced by an animal's state of arousal. Alterations in the dynamic characteristics of the horizontal vestibulo-ocular reflex of adolescent rhesus monkeys induced by changes in the animal's state of arousal were studied using linear system analysis employing both single frequency sinusoidal and white noise rotational stimulations. Arousal changes were induced by a behavioral task and/or the administration of amphetamines (0.5 mg/kg). Results indicate that highly alert animals display vestibulo-ocular reflex gains significantly different from less alert animals. Specifically, the gain of the vestibulo-ocular reflex is closer to unity over a wider range of frequencies in more alert animals. These changes were independent of the method used to maintain a high level of arousal. PMID:7214148

  2. Head Movements Evoked in Alert Rhesus Monkey by Vestibular Prosthesis Stimulation: Implications for Postural and Gaze Stabilization

    PubMed Central

    Mitchell, Diana E.; Dai, Chenkai; Rahman, Mehdi A.; Ahn, Joong Ho; Della Santina, Charles C.; Cullen, Kathleen E.

    2013-01-01

    The vestibular system detects motion of the head in space and in turn generates reflexes that are vital for our daily activities. The eye movements produced by the vestibulo-ocular reflex (VOR) play an essential role in stabilizing the visual axis (gaze), while vestibulo-spinal reflexes ensure the maintenance of head and body posture. The neuronal pathways from the vestibular periphery to the cervical spinal cord potentially serve a dual role, since they function to stabilize the head relative to inertial space and could thus contribute to gaze (eye-in-head + head-in-space) and posture stabilization. To date, however, the functional significance of vestibular-neck pathways in alert primates remains a matter of debate. Here we used a vestibular prosthesis to 1) quantify vestibularly-driven head movements in primates, and 2) assess whether these evoked head movements make a significant contribution to gaze as well as postural stabilization. We stimulated electrodes implanted in the horizontal semicircular canal of alert rhesus monkeys, and measured the head and eye movements evoked during a 100ms time period for which the contribution of longer latency voluntary inputs to the neck would be minimal. Our results show that prosthetic stimulation evoked significant head movements with latencies consistent with known vestibulo-spinal pathways. Furthermore, while the evoked head movements were substantially smaller than the coincidently evoked eye movements, they made a significant contribution to gaze stabilization, complementing the VOR to ensure that the appropriate gaze response is achieved. We speculate that analogous compensatory head movements will be evoked when implanted prosthetic devices are transitioned to human patients. PMID:24147142

  3. Rhesus monkey platelets

    SciTech Connect

    Harbury, C.B.

    1986-03-01

    The purpose of this abstract is to describe the adenine nucleotide metabolism of Rhesus monkey platelets. Nucleotides are labelled with /sup 14/C-adenine and extracted with EDTA-ethanol (EE) and perchlorate (P). Total platelet ATP and ADP (TATP, TADP) is measured in the Holmsen Luciferase assay, and expressed in nanomoles/10/sup 8/ platelets. TR=TATP/TADP. Human platelets release 70% of their TADP, with a ratio of released ATP/ADP of 0.7. Rhesus platelets release 82% of their TADP, with a ratio of released ATP/ADP of 0.33. Thus, monkey platelets contain more ADP than human platelets. Thin layer chromatography of EE gives a metabolic ratio of 11 in human platelets and 10.5 in monkey platelets. Perchlorate extracts metabolic and actin bound ADP. The human and monkey platelets ratios were 5, indicating they contain the same proportion of actin. Thus, the extra ADP contained in monkey platelets is located in the secretory granules.

  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. 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. PMID:27388917

  6. 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.

  7. Vitreal syneresis in rhesus monkeys.

    PubMed

    Stuck, B E; Talsma, D M; Beatrice, E S

    1977-11-01

    The eyes of 15 rhesus monkeys were evaluated. Various degrees of vitreal syneresis were observed in 28 of the 30 eyes. The observed vitreal structures varied from fine strands randomly spaced throughout the vitreous to thick, intertwining, fibrous networks with some clumping of the collagenous condensate at the fiber junctions. Qualitatively, the degree of syneresis was slightly more extensive in the eight older mature males than in the seven younger animals. In all animals a clear view of the fundus could be obtained with the ophthalmoscope. The vitreous structures may be one cause of variability in ocular dose-response relationships for exposure to laser radiation. The effect on retinal exposure experiments of the finer vitreal structure is considered minimal.

  8. Generation of Chimeric Rhesus Monkeys

    PubMed Central

    Tachibana, Masahito; Sparman, Michelle; Ramsey, Cathy; Ma, Hong; Lee, Hyo-Sang; Penedo, Maria Cecilia T.; Mitalipov, Shoukhrat

    2011-01-01

    Summary Totipotent cells in early embryos are progenitors of all stem cells and are capable of developing into a whole organism, including extraembryonic tissues such as placenta. Pluripotent cells in the inner cell mass (ICM) are the descendants of totipotent cells and can differentiate into any cell type of a body except extraembryonic tissues. The ability to contribute to chimeric animals upon reintroduction into host embryos is the key feature of murine totipotent and pluripotent cells. Here, we demonstrate that rhesus monkey embryonic stem cells (ESCs) and isolated ICMs fail to incorporate into host embryos and develop into chimeras. However, chimeric offspring were produced following aggregation of totipotent cells of the 4-cell embryos. These results provide insights into the species-specific nature of primate embryos and suggest that a chimera assay using pluripotent cells may not be feasible. PMID:22225614

  9. 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.

  10. 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.

  11. 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

  12. Sequential planning in rhesus monkeys (Macaca mulatta)

    PubMed Central

    Danly, Erin; Morgan, Gin; Colombo, Michael; Terrace, Herbert S.

    2014-01-01

    In the current study, we examined the planning abilities of rhesus monkeys (Macaca mulatta) by training them on a five-item list composed of coloured photographs and then testing them on switch and mask trials. In contrast to previous studies where monkeys made responses using a joystick, in the current study, monkeys made responses directly to a touch screen. On switch trials, after a response to the first list item, the on-screen positions of two list items were exchanged. Performance on trials in which the second and third list items were exchanged was poorer compared to normal (non-switch) trials for all subjects. When the third and fourth items were exchanged, however, only one subject continued to show performance deficits. On mask trials, following a response to the first item, the remaining items were covered by opaque white squares. When two items were masked, all four subjects responded to each masked item at a level significantly above chance. When three items were masked, however, only one subjected was able to respond to all three masked items at a level significantly above chance. The results of the present study indicate that three of our four monkeys planned one response ahead while a single monkey planned two responses ahead. The significance of these findings is discussed in relation to previous studies on planning in chimpanzees and monkeys. PMID:21184125

  13. 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…

  14. 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.

  15. Volume effects in Rhesus monkey spinal cord

    SciTech Connect

    Schultheiss, T.E. ); Stephens, L.C.; Price, R.E.; Ang, K.K.; Peters, L.J. )

    1994-04-30

    An experiment was conducted to test for the existence of a volume effect in radiation myelopathy using Rhesus monkeys treated with clinically relevant field sizes and fractionation schedules. Five groups of Rhesus monkeys were irradiated using 2.2 Gy per fraction to their spinal cords. Three groups were irradiated with 8 cm fields to total doses of 70.4, 77, and 83.6 Gy. Two additional groups were irradiated to 70.4 Gy using 4 and 16 cm fields. The incidence of paresis expressed within 2 years following the completion of treatment was determined for each group. Maximum likelihood estimation was used to determine parameters of a logistic dose response function. The volume effect was modeled using the probability model in which the probability of producing a lesion in an irradiated volume is governed by the probability of the occurrence of independent events. This is a two parameter model requiring only the estimates of the parameters of the dose-response function for the reference volume, but not needing any additional parameters for describing the volume effect. The probability model using a logistic dose-response function fits the data well with the D[sub 50] = 75.8 Gy for the 8-cm field. No evidence was seen for a difference in sensitivities for different anatomical levels of the spinal cord. Most lesions were type 3, combined white matter parenchymal and vascular lesions. Latent periods did not differ significantly from those of type 3 lesions in humans. The spinal cord exhibits a volume effect that is well described by the probability model. Because the dose response function for radiation myelopathy is steep, the volume effect is modest. The Rhesus monkey remains the animal model most similar to humans in dose response, histopathology, and latency for radiation myelopathy. 22 refs., 3 figs., 1 tab.

  16. Can Rhesus Monkey Learn Executive Attention?

    PubMed Central

    Bramlett-Parker, Jessica; Washburn, David A.

    2016-01-01

    A growing body of data indicates that, compared to humans, rhesus monkeys perform poorly on tasks that assess executive attention, or voluntary control over selection for processing, particularly under circumstances in which attention is attracted elsewhere by competing stimulus control. In the human-cognition literature, there are hotly active debates about whether various competencies such as executive attention, working memory capacity, and fluid intelligence can be improved through training. In the current study, rhesus monkeys (Macaca mulatta) completed an attention-training intervention including several inhibitory-control tasks (a Simon task, numerical Stroop task, global/local interference task, and a continuous performance task) to determine whether generalized improvements would be observed on a version of the Attention Network Test (ANT) of controlled attention, which was administered before and after the training intervention. Although the animals demonstrated inhibition of prepotent responses and improved in executive attention with practice, this improvement did not generalize to the ANT at levels consistently better than were observed for control animals. Although these findings fail to encourage the possibility that species differences in cognitive competencies can be ameliorated through training, they do advance our understanding of the competition between stimulus-control and cognitive-control in performance by nonhuman and human primates. PMID:27304969

  17. Extinction Deficits in Socially Isolated Rhesus Monkeys (Macaca mulatta)

    ERIC Educational Resources Information Center

    Gluck, John P.; Sackett, Gene P.

    1976-01-01

    Rhesus monkeys were reared in total isolation, in partial isolation, or under normal conditions with access to mothers and peers. Each group was compared on the rate of acquisition of a simple operant response. (GO)

  18. Automatic brain segmentation in rhesus monkeys

    NASA Astrophysics Data System (ADS)

    Styner, Martin; Knickmeyer, Rebecca; Joshi, Sarang; Coe, Christopher; Short, Sarah J.; Gilmore, John

    2007-03-01

    Many neuroimaging studies are applied to primates as pathologies and environmental exposures can be studied in well-controlled settings and environment. In this work, we present a framework for both the semi-automatic creation of a rhesus monkey atlas and a fully automatic segmentation of brain tissue and lobar parcellation. We determine the atlas from training images by iterative, joint deformable registration into an unbiased average image. On this atlas, probabilistic tissue maps and a lobar parcellation. The atlas is then applied via affine, followed by deformable registration. The affinely transformed atlas is employed for a joint T1/T2 based tissue classification. The deformed atlas parcellation masks the tissue segmentations to define the parcellation. Other regional definitions on the atlas can also straightforwardly be used as segmentation. We successfully built average atlas images for the T1 and T2 datasets using a developmental training datasets of 18 cases aged 16-34 months. The atlas clearly exhibits an enhanced signal-to-noise ratio compared to the original images. The results further show that the cortical folding variability in our data is highly limited. Our segmentation and parcellation procedure was successfully re-applied to all training images, as well as applied to over 100 additional images. The deformable registration was able to identify corresponding cortical sulcal borders accurately. Even though the individual methods used in this segmentation framework have been applied before on human data, their combination is novel, as is their adaptation and application to rhesus monkey MRI data. The reduced variability present in the primate data results in a segmentation pipeline that exhibits high stability and anatomical accuracy.

  19. Delay discounting of saccharin in rhesus monkeys.

    PubMed

    Freeman, Kevin B; Green, Leonard; Myerson, Joel; Woolverton, William L

    2009-10-01

    The value of a reinforcer decreases as the time until its receipt increases, a phenomenon referred to as delay discounting. Although delay discounting of non-drug reinforcers has been studied extensively in a number of species, our knowledge of discounting in non-human primates is limited. In the present study, rhesus monkeys were allowed to choose in discrete trials between 0.05% saccharin delivered in different amounts and with different delays. Indifference points were calculated and discounting functions were established. Discounting functions for saccharin were well described by a hyperbolic function. Moreover, the discounting rates for saccharin in all six monkeys were comparable to those of other non-human animals responding for non-drug reinforcers. Also consistent with other studies of non-human animals, changing the amount of a saccharin reinforcer available after a 10-s delay did not affect its relative subjective value. Discounting functions for saccharin were steeper than we found in a previous study with cocaine, raising the possibility that drugs such as cocaine may be discounted less steeply than non-drug reinforcers. PMID:19540317

  20. Delay discounting of cocaine by rhesus monkeys.

    PubMed

    Woolverton, William L; Myerson, Joel; Green, Leonard

    2007-06-01

    The present, subjective value of a reinforcer typically decreases as a function of the delay to its receipt, a phenomenon termed delay discounting. Delay discounting, which is assumed to reflect impulsivity, is hypothesized to play an important role in drug abuse. The present study examined delay discounting of cocaine injections by rhesus monkeys. Subjects were studied on a discrete-trials task in which they chose between 2 doses of cocaine: a smaller, immediate dose and a larger, delayed dose. The immediate dose varied between 0.012 and 0.4 mg/kg/injection, whereas the delayed dose was always 0.2 mg/kg/injection and was delivered after a delay that varied between 0 and 300 s in different conditions. At each delay, the point at which a monkey chose the immediate and delayed doses equally often (i.e., the ED50) provided a measure of the present, subjective value of the delayed dose. Dose-response functions for the immediate dose shifted to the left as delay increased. The amount of the immediate dose predicted to be equal in subjective value to the delayed dose decreased as a function of the delay, and hyperbolic discounting functions provided good fits to the data (median R(2)=.86). The current approach may provide the basis for an animal model of the effect of delay on the subjective value of drugs of abuse. PMID:17563210

  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. 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.

  3. 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.

  4. Delay discounting of saccharin in rhesus monkeys.

    PubMed

    Freeman, Kevin B; Green, Leonard; Myerson, Joel; Woolverton, William L

    2009-10-01

    The value of a reinforcer decreases as the time until its receipt increases, a phenomenon referred to as delay discounting. Although delay discounting of non-drug reinforcers has been studied extensively in a number of species, our knowledge of discounting in non-human primates is limited. In the present study, rhesus monkeys were allowed to choose in discrete trials between 0.05% saccharin delivered in different amounts and with different delays. Indifference points were calculated and discounting functions were established. Discounting functions for saccharin were well described by a hyperbolic function. Moreover, the discounting rates for saccharin in all six monkeys were comparable to those of other non-human animals responding for non-drug reinforcers. Also consistent with other studies of non-human animals, changing the amount of a saccharin reinforcer available after a 10-s delay did not affect its relative subjective value. Discounting functions for saccharin were steeper than we found in a previous study with cocaine, raising the possibility that drugs such as cocaine may be discounted less steeply than non-drug reinforcers.

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

    DOE PAGES

    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; et al

    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

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

    SciTech Connect

    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.

    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 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.

  7. 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…

  8. 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

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

    PubMed

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

    2015-02-01

    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.

  10. 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. PMID:24795661

  11. Social separation increases alcohol consumption in rhesus monkeys.

    PubMed

    Kraemer, G W; McKinney, W T

    1985-01-01

    This study used 16 socially reared juvenile rhesus monkeys as subjects to test the hypothesis that social separation promotes alcohol consumption in this species. In the first part of the study, 12 monkeys were intermittently separated from their social groups, while 4 were separated before the beginning of the study and remained continuously separated. Refrigerated water or aspartame-sweetened water (vehicle) containing 6% alcohol (w/v) were presented after 4.5 h of fluid deprivation. Intermittently separated monkeys drank more alcohol during separation than when they were socially housed, and more than the continuously separated monkeys. Stable individual differences in consumption rate developed over repeated separations. These differences were not correlated with consumption of refrigerated water or vehicle, or with differential behavioral (locomotor) responses to social separation. This suggested that some monkeys were predisposed to drink more alcohol than others. The second part of the study determined whether established alcohol/vehicle consumption rates for all 16 monkeys were altered when the monkeys were not water deprived, and then when water and the vehicle were available at the same time as alcohol/vehicle. Among monkeys that drank the most (mean of 2.4 g/kg/h) and the least (mean of 0.8 g/kg/h), alcohol consumption was not affected. These results, combined with previous reports, suggest a neurobiological linkage between genetically based social attachment mechanisms, social stressors, and vulnerability to alcohol abuse and addiction in primates.

  12. Music perception and octave generalization in rhesus monkeys.

    PubMed

    Wright, A A; Rivera, J J; Hulse, S H; Shyan, M; Neiworth, J J

    2000-09-01

    Two rhesus monkeys were tested for octave generalization in 8 experiments by transposing 6- and 7-note musical passages by an octave and requiring same or different judgments. The monkeys showed no octave generalization to random-synthetic melodies, atonal melodies, or individual notes. They did show complete octave generalization to childhood songs (e.g., "Happy Birthday") and tonal melodies (from a tonality algorithm). Octave generalization was equally strong for 2-octave transpositions but not for 0.5- or 1.5-octave transpositions of childhood songs. These results combine to show that tonal melodies form musical gestalts for monkeys, as they do for humans, and retain their identity when transposed with whole octaves so that chroma (key) is preserved. This conclusion implicates similar transduction, storage, processing, and relational memory of musical passages in monkeys and humans and has implications for nature-nurture origins of music perception. PMID:11006902

  13. 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.

  14. A restraining system for rhesus monkeys used in space research.

    PubMed

    Florence, G; Riondet, L; Malecki, H; Blanquie, J P; Martin, F; Viso, M; Milhaud, C L

    1995-02-01

    A new chronic restraining system has been designed specifically for male rhesus monkeys (8-13 kg) housed in weightlessness for scientific purposes. The restraining system consists of a coat (jacket and skirt) and a chair. The system separates the thorax from the lower part of the body, and allows large movements of the upper part of the body. The macaque can feed and groom itself, and can also sleep in close-to-normal position. PMID:8613974

  15. Noninvasive scalp recording of cortical auditory evoked potentials in the alert macaque monkey.

    PubMed

    Itoh, Kosuke; Nejime, Masafumi; Konoike, Naho; Nakada, Tsutomu; Nakamura, Katsuki

    2015-09-01

    Scalp-recorded evoked potentials (EP) provide researchers and clinicians with irreplaceable means for recording stimulus-related neural activities in the human brain, due to its high temporal resolution, handiness, and, perhaps more importantly, non-invasiveness. This work recorded the scalp cortical auditory EP (CAEP) in unanesthetized monkeys by using methods that are essentially identical to those applied to humans. Young adult rhesus monkeys (Macaca mulatta, 5-7 years old) were seated in a monkey chair, and their head movements were partially restricted by polystyrene blocks and tension poles placed around their head. Individual electrodes were fixated on their scalp using collodion according to the 10-20 system. Pure tone stimuli were presented while electroencephalograms were recorded from up to nineteen channels, including an electrooculogram channel. In all monkeys (n = 3), the recorded CAEP comprised a series of positive and negative deflections, labeled here as macaque P1 (mP1), macaque N1 (mN1), macaque P2 (mP2), and macaque N2 (mN2), and these transient responses to sound onset were followed by a sustained potential that continued for the duration of the sound, labeled the macaque sustained potential (mSP). mP1, mN2 and mSP were the prominent responses, and they had maximal amplitudes over frontal/central midline electrode sites, consistent with generators in auditory cortices. The study represents the first noninvasive scalp recording of CAEP in alert rhesus monkeys, to our knowledge.

  16. Mononeuropathy multiplex in rhesus monkeys with chronic Lyme disease.

    PubMed

    England, J D; Bohm, R P; Roberts, E D; Philipp, M T

    1997-03-01

    Peripheral neuropathy is a recognized but poorly understood manifestation of Lyme disease. We performed serial electrophysiological studies on 8 rhesus monkeys chronically infected with the JD1 strain of Borrelia burgdorferi and compared the results with those of similar studies on 10 uninfected control monkeys. Four infected and 2 uninfected animals underwent sural nerve biopsy. Five of the infected and 1 of the uninfected animals also had postmortem neuropathological examinations. Altogether, 5 of the infected monkeys demonstrated primarily axonal-loss-variety multifocal neuropathies. Only one nerve lesion exhibited findings compatible with demyelination. Pathologically, peripheral nerve specimens showed multifocal axonal degeneration and regeneration and occasional perivascular inflammatory cellular infiltrates without vessel wall necrosis. Free spirochetal structures were not seen, but several macrophages exhibited positive immunostaining with a highly specific anti-B. burgdorferi, 7.5-kd lipoprotein monoclonal antibody. In the infected animals, serial analysis of serum antibodies to B. burgdorferi showed increasing numbers of IgG specificities and new IgM specificities, suggesting persistent infection. Thus, peripheral neuropathy in the form of a mononeuropathy multiplex develops frequently in rhesus monkeys chronically infected with B. burgdorferi. The pathogenesis of these nerve lesions is not yet known, but our studies suggest an immune-mediated process perhaps driven by persistent infection with B. burgdorferi.

  17. Operant discrimination of an interoceptive stimulus in rhesus monkeys1

    PubMed Central

    Slucki, Henry; Adam, Gyorgi; Porter, Robert W.

    1965-01-01

    Five rhesus macaques monkeys surgically prepared with Thiry small intestinal (jejunum) loops and implanted brain electrodes were restrained in primate chairs and kept on 23-hr deprivation-feeding cycle. After being trained to press a lever for sugar pills on an FR 25 schedule of reinforcement, a discrimination training procedure was established. Lever presses were reinforced during the SD—a non-aversive mechanical stimulus applied to the internal walls of the Thiry loop by rhythmic inflation-deflation of a small latex balloon by air at the rate of one cycle per sec at 100 mm Hg pressure. The SΔ was the absence of the visceral stimulation. The monkeys successfully discriminated between presence and absence of the internal stimulus. A discrimination reversal was attempted and completed on one monkey. The results clearly show operant discrimination based on an interoceptive stimulus. Cortical and subcortical EEG records reflected the onset but not termination of the visceral stimulation. PMID:4954822

  18. Color-detection thresholds in rhesus macaque monkeys and humans.

    PubMed

    Gagin, Galina; Bohon, Kaitlin S; Butensky, Adam; Gates, Monica A; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L; Qu, Jane; Stoughton, Cleo M; Swanbeck, Sonja N; Conway, Bevil R

    2014-07-15

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection thresholds from initial testing to plateau performance (“learning”) was similar for +L − M (red) colors and +M − L (bluish-green) colors. But the extent of learning was higher for +S (lavender) than for −S (yellow-lime); moreover, at plateau performance, the cone contrast at the detection threshold was higher for +S than for −S. These asymmetries may reflect differences in retinal circuitry for S-ON and S-OFF. At plateau performance, the two species also had similar detection thresholds for all colors, although monkeys had shorter reaction times than humans and slightly lower thresholds for colors that modulated L/M cones. We discuss whether these observations, together with previous work showing that monkeys have lower spatial acuity than humans, could be accounted for by selective pressures driving higher chromatic sensitivity at the cost of spatial acuity amongst monkeys, specifically for the more recently evolved L − M mechanism.

  19. 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.

  20. Facial expression recognition in rhesus monkeys, Macaca mulatta.

    PubMed

    Parr, Lisa A; Heintz, Matthew

    2009-06-01

    The ability to recognize and accurately interpret facial expressions is critically important for nonhuman primates that rely on these nonverbal signals for social communication. Despite this, little is known about how nonhuman primates, particularly monkeys, discriminate between facial expressions. In the present study, seven rhesus monkeys were required to discriminate four categories of conspecific facial expressions using a matching-to-sample task. In experiment 1, the matching pair showed identical photographs of facial expressions, paired with every other expression type as the nonmatch. The identity of the nonmatching stimulus monkey differed from the one in the sample. Subjects performed above chance on session 1, with no difference in performance across the four expression types. In experiment 2, the identity of all three monkeys differed in each trial, and a neutral portrait was also included as the nonmatching stimulus. Monkeys discriminated expressions across individual identity when the non-match was a neutral stimulus, but they had difficulty when the nonmatch was another expression type. We analysed the degree to which specific feature redundancy could account for these error patterns using a multidimensional scaling analysis which plotted the perceived dissimilarity between expression dyads along a two-dimensional axis. One axis appeared to represent mouth shape, stretched open versus funnelled, while the other appeared to represent a combination of lip retraction and mouth opening. These features alone, however, could not account for overall performance and suggest that monkeys do not rely solely on distinctive features to discriminate among different expressions. PMID:20228886

  1. Color-detection thresholds in rhesus macaque monkeys and humans

    PubMed Central

    Gagin, Galina; Bohon, Kaitlin S.; Butensky, Adam; Gates, Monica A.; Hu, Jiun-Yiing; Lafer-Sousa, Rosa; Pulumo, Reitumetse L.; Qu, Jane; Stoughton, Cleo M.; Swanbeck, Sonja N.; Conway, Bevil R.

    2014-01-01

    Macaque monkeys are a model of human color vision. To facilitate linking physiology in monkeys with psychophysics in humans, we directly compared color-detection thresholds in humans and rhesus monkeys. Colors were defined by an equiluminant plane of cone-opponent color space. All subjects were tested on an identical apparatus with a four-alternative forced-choice task. Targets were 2° square, centered 2° from fixation, embedded in luminance noise. Across all subjects, the change in detection thresholds from initial testing to plateau performance (“learning”) was similar for +L − M (red) colors and +M − L (bluish-green) colors. But the extent of learning was higher for +S (lavender) than for −S (yellow-lime); moreover, at plateau performance, the cone contrast at the detection threshold was higher for +S than for −S. These asymmetries may reflect differences in retinal circuitry for S-ON and S-OFF. At plateau performance, the two species also had similar detection thresholds for all colors, although monkeys had shorter reaction times than humans and slightly lower thresholds for colors that modulated L/M cones. We discuss whether these observations, together with previous work showing that monkeys have lower spatial acuity than humans, could be accounted for by selective pressures driving higher chromatic sensitivity at the cost of spatial acuity amongst monkeys, specifically for the more recently evolved L − M mechanism. PMID:25027164

  2. 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

  3. Hot-hand bias in rhesus monkeys.

    PubMed

    Blanchard, Tommy C; Wilke, Andreas; Hayden, Benjamin Y

    2014-07-01

    Human decision-makers often exhibit the hot-hand phenomenon, a tendency to perceive positive serial autocorrelations in independent sequential events. The term is named after the observation that basketball fans and players tend to perceive streaks of high accuracy shooting when they are demonstrably absent. That is, both observing fans and participating players tend to hold the belief that a player's chance of hitting a shot are greater following a hit than following a miss. We hypothesize that this bias reflects a strong and stable tendency among primates (including humans) to perceive positive autocorrelations in temporal sequences, that this bias is an adaptation to clumpy foraging environments, and that it may even be ecologically rational. Several studies support this idea in humans, but a stronger test would be to determine whether nonhuman primates also exhibit a hot-hand bias. Here we report behavior of 3 monkeys performing a novel gambling task in which correlation between sequential gambles (i.e., temporal clumpiness) is systematically manipulated. We find that monkeys have better performance (meaning, more optimal behavior) for clumped (positively correlated) than for dispersed (negatively correlated) distributions. These results identify and quantify a new bias in monkeys' risky decisions, support accounts that specifically incorporate cognitive biases into risky choice, and support the suggestion that the hot-hand phenomenon is an evolutionary ancient bias.

  4. 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.

  5. Temperature and adrenocortical responses in rhesus monkeys exposed to microwaves

    SciTech Connect

    Lotz, W.G.; Podgorski, R.P.

    1982-12-01

    To determine if the endocrine response to microwave exposure was similar in a primate to that reported for other animals, rectal temperature and plasma levels of cortisol, thyroxine (T4), and growth hormone (GH) were measured in rhesus monkeys exposed to 1.29-GHz microwave radiation. Exposures were carried out under far-field conditions with the monkey restrained in a chair. Incident power densities of 0, 20, 28, and 38 mW/sq cm were used, with corresponding specific absorption rates of 0, 2.1, 3.0, and 4.1 W/kg. Blood samples were taken hourly via an indwelling jugular venous catheter over a 24-h period before, during, and after an 8-h exposure. Rectal temperature increased an average of 0.5, 0.7, and 1.7 C for the three intensities used. No changes in T4 or GH were observed. Cortisol levels were increased during exposure to 38 mW/sq cm. It was concluded that the temperature and adrenocortical responses to microwave exposure of the rhesus monkey are similar to the corresponding responses of other animals.

  6. Hair pulling and eating in captive rhesus monkey troops.

    PubMed

    Reinhardt, V; Reinhardt, A; Houser, D

    1986-01-01

    Hair pulling and eating has not yet received attention in the nonhuman primate literature. Hair pulling and eating was recorded 388 times in two heterogeneous troops of healthy rhesus monkeys that were kept according to modern management practices. The behavior in question consists of the following sequence: pulling with the fingers (1/3 of cases) or with the teeth (2/3 of cases) tufts of hair from one's own or from a partner's coat; chewing the hair and finally swallowing it; the undigested material is excreted in the feces. Hair pulling was almost exclusively (378/388) partner-directed. It was observed 364 times between animals whose dominance relationships were known; it was performed in 96% (349/364) of observations by a dominant but only in 4% (15/364) of observations by a subordinate monkey. The recipient of hair pulling showed typical fear and/or avoidance reactions. In both troops young animals (2-8 years of age) engaged in hair pulling and eating significantly more often than old animals (10-26 years of age). There was no evidence that nutritional, toxicological or climatic factors were responsible for the manifestation of this behavior. It was concluded that, similar to trichotillomania in man, wool pulling and eating in sheep and muskox, and feather picking in poultry, hair pulling and eating is an aggressive behavioral disorder in rhesus monkeys reflecting adjustment problems to a stressful environment. PMID:3583152

  7. Endocrine responses in the rhesus monkey during acute cold exposure

    SciTech Connect

    Lotz, W.G.; Saxton, J.L. )

    1991-03-11

    The authors studied five young male rhesus monkeys (Macaca mulatta), 3.4 to 6.7 kg, to determine the relationship between fluid balance hormones and urine production during acute, dry cold exposure. Each monkey served as its own control in duplicate experimental sessions at 6C or 26C. A 6-h experimental session consisted of 120 min equilibration at 26C, 120 min experimental exposure, and 120 min recovery at 26C. Urinary and venous catheters were inserted on the morning of a session. Rectal (Tre) and skin temperatures were monitored continuously. Blood samples were taken at 0, 30, 60 and 120 min of exposure, and at 60 min postexposure. Plasma was analyzed for arginine vasopressin (AVP), atrial natriuretic factor (ANF), plasma renin activity (PRA), plasma aldosterone (PA), and osmolality. Urine samples were analyzed for osmolality, electrolytes, and creatinine. Mean Tre was 1.6C lower after 120 min at 6C than at 26C. Urine volume and osmolality were not altered by cold exposure, as they are in humans and rats. Vasopressin and PA increased sharply, with mean plasma levels in monkeys exposed to cold more than threefold and tenfold, respectively, the levels in monkeys exposed at 26C. In contrast, ANF, PRA, and plasma osmolality were not significantly changed by cold exposure. The absence of a cold-induced diuresis in the monkey may be related to the marked increase in plasma AVP level.

  8. 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. PMID:24367036

  9. 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

  10. 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.

  11. 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.

  12. [Preliminary study on xenotransfusion from porcine red blood cell into Rhesus monkey].

    PubMed

    Tan, Ying-Xia; Ji, Shou-Ping; Lu, Yan-Ping; Zhang, Cheng-Lin; Li, Li-Li; Gong, Feng; Zhang, Jin-Guo; Zhang, Yang-Pei

    2006-02-01

    In order to study the possibility of xenotransfusion from porcine red blood cell (pRBC) to primate, the antigens on pRBC surface were modified to make it more compatible to primate sera. Porcine RBCs were subjected to both enzymatic removal of membrane alpha-Gal antigens with recombinant alpha-galactosidase (AGL) and covalent attachment of succinimid propionate-linked methoxypolyethyleneglycol (mPEG-SPA) to camouflage non-alphaGal antigens. The effects of double modifications were determinated by hemagglutination and clinical cross-match testing with rhesus sera. In vivo clearance rates and safety of modified pRBCs were measured after it was transfused into Rhesus monkey with or without immunosuppressant treatment. The validity of pRBC was detected in exsanguine Rhesus monkey model. The results showed that AGL could effectively remove alpha-Gal xenoantigens on pRBC membrane and reduce hemagglutination. The combination of mPEG modification with AGL treatment could significantly increased compatibility between pRBCs and Rhesus monkey sera. Modified pRBCs were detectable in Rhesus monkey blood at 12 hours after transfusion, and their survival time was 40 hours in the immunosuppressant-treated Rhesus monkey. In vivo survival rates of pRBCs were 38% in exsanguine Rhesus monkey at 8 hours after transfusion, and during that time, the hemoglobin and hematocrit of Rhesus monkey were maintained at the same level as before it lost blood. It is concluded that the modified pRBC can be safely transfused into Rhesus monkey and relieve the anemic symptom exsanguine Rhesus monkey. It suggested that pRBC can be hopefully used as a blood substitute for primate and human in the future.

  13. Cerebrovascular amyloidosis in squirrel monkeys and rhesus monkeys: apolipoprotein E genotype.

    PubMed

    Morelli, L; Wei, L; Amorim, A; McDermid, J; Abee, C R; Frangione, B; Walker, L C; Levy, E

    1996-01-29

    Some neuropathological changes characteristic of aging and Alzheimer's disease (AD) in humans are present also in senescent non-human primates. The human apoE4 allele is associated with an increased risk of developing late-onset familial and sporadic AD. We found that rhesus monkeys and three subspecies of squirrel monkeys are homozygous for apoE phenotype with arginine at positions 112 and 158 as in human apoE4. However, in both species threonine replaces arginine at position 61 of human apoE. It was previously shown that arginine 61 was critical in determining apoE4 lipoprotein distribution in humans.

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

    PubMed Central

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

    2015-01-01

    During the last decade, visual illusions have been used repeatedly to understand similarities and differences of 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 vs. 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 Exp. 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. PMID:25812828

  15. Retinohypothalamic connections in the rhesus monkey

    NASA Astrophysics Data System (ADS)

    Chijuka, John C.

    Previous studies of retinohypothalamic projections in macaques were performed with anterograde degeneration or autoradiographic techniques that were not sufficiently sensitive to fully define these projections. Results of studies in non-primates using sensitive tracers have revealed more extensive retinohypothalamic projection than previously seen. We hypothesize that there are more extensive retinohypothalamic projections in the higher primate, macaque monkey. Thus, the primary goal of this investigation was to characterize the retinohypothalamic projections in the macaque monkey using the more sensitive tract tracer, cholera toxin subunit B (CTB) unilaterally injected intravitreally. Secondary goals were to determine: (1) whether there is a retinal projection to the sleep-related ventrolateral preoptic area of the hypothalamus; (2) whether there are direct retinal projections to gonadotropin-releasing hormone neurons in the hypothalamus; and (3) whether any retinally-projecting hypothalamic neurons can be retrogradely labeled by intravitreal CTB injections. Our results confirmed our hypothesis that there are more extensive projections to the central targets. We found that, in addition to the well-described retinal projection to the suprachiasmatic nucleus, a number of other hypothalamic areas were labeled. We observed projections to the medial and lateral preoptic areas, including the sleep-related ventrolateral preoptic area. A number of retinal fibers terminated immediately dorsal to the supraoptic nucleus (SO), with a few fibers penetrating and terminating within the nucleus. A few fibers continued laterally beyond the SO into the substantia innominata immediately ventral to the nucleus basalis of Meynert. In addition, a dense plexus of CTB-labeled, retinal fibers were present in the subventricular nucleus and adjacent subventricular area. Some of these fibers coursed dorsally from this region to penetrate the ependyma lining the third ventricle and apparently

  16. Pathology of chronic Bolivian hemorrhagic fever in the rhesus monkey.

    PubMed Central

    Mcleod, C. G.; Stookey, J. L.; Eddy, G. A.; Scott, K.

    1976-01-01

    Gross and microscopic lesions of Bolivian hemorrhagic fever (BHF) are described in 10 rhesus monkeys that survived from 30 to 78 days after subcutaneous inoculation with a dose of 10(3) plaque-forming units (PFU) of Machupo virus, a dose which produces a severe and generally fatal disease. Six of the monkeys had been given low doses of homologous immune globulin when initial signs of infection appeared. Monkeys exhibited clinical signs in two phases. The initial signs of acute infection which began to appear about 1 week following inoculation included: diarrhea, depression, anorexia, dehydration, and skin rash. The survivors of this early phase of the illness usually showed improvement before relapsing into the second (or chronic) phase, which was characterized clinically by central nervous system disturbances including incoordination, tremors, convulsions, paresis, and muscle atrophy. Microscopic lesions were similar in both immune globulin-treated and untreated animals. These included widespread lymphoreticular infiltrates in the walls and adventitia of blood vessels of the brain, spinal cord, pancreas, intestine, liver kidney, adrenal, parathyroid, heart, and skeletal muscle. Diffuse lymphocytic infiltrates not confined to the vascular or perivascular tissues were present to a variable degree in many of these and other organs. Several monkeys exhibited lymphocytic inflammation of the choroid, meninges, peripheral nerves, and ganglia. Images Figure 7 Figure 8 Figure 1 Figure 2 Figure 9 Figure 3 Figure 4 Figure 5 Figure 6 PMID:181994

  17. Individual differences in rhesus monkeys' demand for drugs of abuse.

    PubMed

    Koffarnus, Mikhail N; Hall, Amy; Winger, Gail

    2012-09-01

    A relatively small percentage of humans who are exposed to drugs of abuse eventually become addicted to or dependent on those drugs. These individual differences in likelihood of developing drug addiction may reflect behavioral, neurobiological or genetic correlates of drug addiction and are therefore important to model. Behavioral economic measures of demand establish functions whose overall elasticity (rate of decrease in consumption as price increases) reflects the reinforcing effectiveness of various stimuli, including drugs. Using these demand functions, we determined the reinforcing effectiveness of five drugs of abuse (cocaine, remifentanil, ketamine, methohexital and ethanol) in 10 rhesus monkeys with histories of intravenous drug-taking. There was a continuum of reinforcing effectiveness across the five drugs, with cocaine and remifentanil showing the most reinforcing effectiveness. There was also a continuum of sensitivity of the monkeys; two of the 10 animals, in particular, showed greater demand for the drugs than did the remaining eight monkeys. In addition, monkeys that demonstrated greater demand for one drug tended to show greater demand for all drugs but did not show a similar relatively greater demand for sucrose pellets. These findings suggest that the tendency to find drugs to be reinforcing is a general one, not restricted to particular drugs and also, that a minority of animals show a substantially enhanced sensitivity to the reinforcing effects of drugs. The possibility that differences in responsiveness to the reinforcing effects of drugs may form the basis of individual differences in drug-taking in humans should be considered. PMID:21762288

  18. Effects of spaceflight on bone mineralization in the rhesus monkey.

    PubMed

    Zerath, E; Novikov, V; Leblanc, A; Bakulin, A; Oganov, V; Grynpas, M

    1996-07-01

    We combined dual-photon absorptiometry, iliac crest histomorphometry, and backscattered electrons analysis to characterize bone mineralization effects of a spaceflight on young monkeys. Two 4- to 5-kg male rhesus monkeys (Macaca mulatta) were flown during a 11.5-day spaceflight that took place onboard Cosmos 2229 biosatellite (Bion 10). Vivarium (n = 4) and Earth-based chair (n = 4) control situations were studied for comparison. Flight monkeys exhibited lower values of iliac cancellous bone volume, associated with nonsignificantly thinner trabeculae. Bone mineralization rate and the proportion of trabecular bone surface involved in mineralization processes were found markedly reduced after spaceflight. Analysis of embedded sections by backscattered electrons imaging showed a nonsignificant shift to lower mineralization in the flight biopsies vs. postflight mock-up biopsies. These results were in accordance with dual-photon absorptiometry evaluations showing a tendency for decreased bone mineral content during flight and recovery thereafter. The ground simulation experiment performed on the same monkeys more than 1 mo after landing suggests that the observed effects were specifically related to spaceflight and that the animals had only partially recovered. Additional animals on future flights will be required to confirm these findings.

  19. In vitro fertilization and embryo transfer in the rhesus monkey.

    PubMed

    Wolf, D P; Vandevoort, C A; Meyer-Haas, G R; Zelinski-Wooten, M B; Hess, D L; Baughman, W L; Stouffer, R L

    1989-08-01

    Twenty-three rhesus monkeys were subjected to 9 days of ovarian hyperstimulation with sequential exposure to human follicle-stimulating hormone (hFSH) and then human luteinizing hormone (hLH) + hFSH. Six animals (26%) did not exhibit sustained, elevated levels of circulating estradiol, primarily due to the occurrence of a premature surge of endogenous LH (n = 4). Seventeen animals (74%) responded with supraphysiologic levels of circulating estradiol (peak value: means = 4480 pg/ml) and received human chorionic gonadotropin (hCG) on Day 10. Oocytes were collected 26 h later by aspiration of large antral follicles. Oocyte quantity (means = 18/animal) and quality (63% mature) were evaluated by in vitro fertilization (IVF), embryonic development, and embryo transfer to foster mothers. Modified conditions for the successful fertilization of oocytes used a Tyrode's augmented (TALP) medium supplemented with 0.3% bovine serum albumin (BSA). Oocytes were inseminated at the metaphase II stage with ejaculated, washed sperm (50 100 x 10(3)/ml) preexposed at ambient temperature to caffeine and dibutyryl cyclic adenosine 3'5'-monophosphate. Successful fertilization ranged from 26% to 75%. In one experiment, 5 of 11 embryos produced by IVF developed in vitro to hatched blastocysts. Embryo freezing employed a propanediol-based protocol and was applied to early cleavage-stage embryos with 100% (5 of 5) post-thaw survival. Two frozen-thawed embryos were transferred transtubally on 3 occasions into rhesus monkeys during the early luteal phase of spontaneous menstrual cycles. One pregnancy resulted, which proceeded normally to the unassisted delivery of a male offspring 170 days after the LH surge. We conclude that this sequential regimen of human gonadotropins provides a cohort of oocytes from rhesus monkeys that will complete meiotic maturation and fertilize in vitro, with embryonic development proceeding in vitro and in vivo. The production of putative antibodies to human

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

    PubMed

    Hopkins, W D; Washburn, D A; Hyatt, C W

    1996-04-01

    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.

  1. An Interval for Studying and Quantifying Social Relations in Pairs of Rhesus Monkeys

    ERIC Educational Resources Information Center

    Maxim, Peter E.

    1976-01-01

    An internal scale of 17 behavior categories was constructed from data on 120 pairs of rhesus monkeys while they were establishing a social relationship. Data were obtained by a procedure analogous to that used in human psychophysical scaling. (Editor)

  2. 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.

  3. 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.

  4. 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.

  5. White Matter Neurons in Young Adult and Aged Rhesus Monkey

    PubMed Central

    Mortazavi, Farzad; Wang, Xiyue; Rosene, Douglas L.; Rockland, Kathleen S.

    2016-01-01

    In humans and non-human primates (NHP), white matter neurons (WMNs) persist beyond early development. Their functional importance is largely unknown, but they have both corticothalamic and corticocortical connectivity and at least one subpopulation has been implicated in vascular regulation and sleep. Several other studies have reported that the density of WMNs in humans is altered in neuropathological or psychiatric conditions. The present investigation evaluates and compares the density of superficial and deep WMNs in frontal (FR), temporal (TE), and parietal (Par) association regions of four young adult and four aged male rhesus monkeys. A major aim was to determine whether there was age-related neuronal loss, as might be expected given the substantial age-related changes known to occur in the surrounding white matter environment. Neurons were visualized by immunocytochemistry for Neu-N in coronal tissue sections (30 μm thickness), and neuronal density was assessed by systematic random sampling. Per 0.16 mm2 sampling box, this yielded about 40 neurons in the superficial WM and 10 in the deep WM. Consistent with multiple studies of cell density in the cortical gray matter of normal brains, neither the superficial nor deep WM populations showed statistically significant age-related neuronal loss, although we observed a moderate decrease with age for the deep WMNs in the frontal region. Morphometric analyses, in contrast, showed significant age effects in soma size and circularity. In specific, superficial WMNs were larger in FR and Par WM regions of the young monkeys; but in the TE, these were larger in the older monkeys. An age effect was also observed for soma circularity: superficial WMNs were more circular in FR and Par of the older monkeys. This second, morphometric result raises the question of whether other age-related morphological, connectivity, or molecular changes occur in the WMNs. These could have multiple impacts, given the wide range of putative

  6. Oxytocin enhances attention to the eye region in rhesus monkeys

    PubMed Central

    Dal Monte, Olga; Noble, Pamela L.; Costa, Vincent D.; Averbeck, Bruno B.

    2014-01-01

    Human and non-human primates rely on the ability to perceive and interpret facial expressions to guide effective social interactions. The neuropeptide oxytocin (OT) has been shown to have a critical role in the perception of social cues, and in humans to increase the number of saccades to the eye region. To develop a useful primate model for the effects of OT on information processing, we investigated the influence of OT on gaze behavior during face processing in rhesus macaques. Forty-five minutes after a single intranasal dose of either 24IU OT or saline, monkeys completed a free-viewing task during which they viewed pictures of conspecifics displaying one of three facial expressions (neutral, open-mouth threat or bared-teeth) for 5 s. The monkey was free to explore the face on the screen while the pattern of eye movements was recorded. OT did not increase overall fixations to the face compared to saline. Rather, when monkeys freely viewed conspecific faces, OT increased fixations to the eye region relative to the mouth region. This effect of OT was particularly pronounced when face position on the screen was manipulated so that the eye region was not the first facial feature seen by the monkeys. Together these findings are consistent with prior evidence in humans that intranasal administration of OT specifically enhances visual attention to the eye region compared to other informative facial features, thus validating the use of non-human primates to mechanistically explore how OT modulates social information processing and behavior. PMID:24624055

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

    SciTech Connect

    Doerge, Daniel R.; Twaddle, Nathan C.; Woodling, Kellie A.; Fisher, Jeffrey W.

    2010-10-01

    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. The 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.

  8. Behavior of rhesus monkeys during artificial menstrual cycles.

    PubMed

    Michael, R P; Zumpe, D; Bonsall, R W

    1982-12-01

    Daily subcutaneous injections of estradiol, progesterone, and testosterone were given to ovariectomized rhesus monkeys in amounts that imitated accurately the changing plasma levels of hormones in intact females with natural menstrual cycles. Because these cycles in ovariectomized, treated females were terminated by normal vaginal bleeding every 28 days and showed a mid-cycle gonadotropin surge, we termed them "artificial menstrual cycles." In dyadic mating tests, changes in the females' access times (lever pressing) for males, and in the males' ejaculatory performance, were closely similar during natural and artificial cycles, and there were well-marked behavioral rhythms. These rhythms were lost during 28-day control periods when ovariectomized females received injections of vehicle alone. Differences in ejaculatory performance during natural and artificial cycles could be accounted for by an order effect. It is concluded that the artificial cycle provides a valid and useful paradigm for a more detailed study of the neuroendocrine regulation of primate reproductive behavior. PMID:7153385

  9. Smoked heroin self-administration in rhesus monkeys.

    PubMed

    Mattox, A J; Carroll, M E

    1996-06-01

    The purpose of the present study was to evaluate behavioral and pharmacological determinants of smoked heroin self-administration. Eight rhesus monkeys were trained to self-administer smoked heroin under a chained fixed-ratio, (FR, 64-1024) for lever presses, FR 5 for inhalations schedule during daily experimental sessions. Demand for heroin was determined by plotting consumption (smoke deliveries) as a function of price which was varied by increasing the FR lever press requirement from 64 to 1024. The heroin demand curve was compared to that obtained with smoked cocaine base. Dose-effect determinations were obtained by varying the unit dose of heroin from 0.025 to 1.6 mg/kg per delivery. Pretreatment with naloxone (0.01-1.0 mg/kg IM, 10 min presession) and substitution tests with the peripherally acting opioid loperamide (0.1 mg/kg per delivery) were also conducted. Deliveries of smoked heroin decreased, but lever responding per delivery increased as the FR increased. Demand for heroin was elastic and comparable to demand for smoked cocaine base. Varying the dose of heroin available for self-administration resulted in an asymptotic dose-effect curve. Naloxone pretreatment produced dose-dependent decreases in heroin self-administration. Substitution of loperamide for heroin produced extinction-like responding within one or two sessions, with the total smoke deliveries decreasing by 80% of heroin levels within 8-15 days. Reinstatement of heroin resulted in a rapid return to baseline levels of self-administration. These data suggest that rhesus monkeys will readily and reliably self-administer heroin via the inhalation route, and behavioral and pharmacological manipulations indicate that smoked heroin functioned as a positive reinforcer.

  10. 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

  11. Evaluation of Rhesus Monkey and Guinea Pig Hepatic Cytosol Fractions as Models for Human Aldehyde Oxidase

    PubMed Central

    Choughule, Kanika V.; Barr, John T.

    2013-01-01

    Aldehyde oxidase (AOX) is a cytosolic enzyme expressed across a wide range of species, including guinea pig and rhesus monkey. These species are believed to be the best preclinical models for studying human AOX-mediated metabolism. We compared AOX activity in rhesus monkeys, guinea pigs, and humans using phthalazine and N-[2-(dimethylamino)ethyl]acridone-4-carboxamide (DACA) as substrates and raloxifene as an inhibitor. Michaelis-Menten kinetics was observed for phthalazine oxidation in rhesus monkey, guinea pig, and human liver cytosol, whereas substrate inhibition was seen with DACA oxidase activity in all three livers. Raloxifene inhibited phthalazine and DACA oxidase activity uncompetitively in guinea pig, whereas mixed-mode inhibition was seen in rhesus monkey. Our analysis of the primary sequence alignment of rhesus monkey, guinea pig, and human aldehyde oxidase isoform 1 (AOX1) along with homology modeling has led to the identification of several amino acid residue differences within the active site and substrate entrance channel of AOX1. We speculate that some of these residues might be responsible for the differences observed in activity. Overall, our data indicate that rhesus monkeys and guinea pigs would overestimate intrinsic clearance in humans and would be unsuitable to use as animal models. Our study also showed that AOX metabolism in species is substrate-dependent and no single animal model can be reliably used to predict every drug response in humans. PMID:23918666

  12. Lethal experimental infections of rhesus monkeys by aerosolized Ebola virus.

    PubMed Central

    Johnson, E.; Jaax, N.; White, J.; Jahrling, P.

    1995-01-01

    The potential of aerogenic infection by Ebola virus was established by using a head-only exposure aerosol system. Virus-containing droplets of 0.8-1.2 microns were generated and administered into the respiratory tract of rhesus monkeys via inhalation. Inhalation of viral doses as low as 400 plaque-forming units of virus caused a rapidly fatal disease in 4-5 days. The illness was clinically identical to that reported for parenteral virus inoculation, except for the occurrence of subcutaneous and venipuncture site bleeding and serosanguineous nasal discharge. Immunocytochemistry revealed cell-associated Ebola virus antigens present in airway epithelium, alveolar pneumocytes, and macrophages in the lung and pulmonary lymph nodes; extracellular antigen was present on mucosal surfaces of the nose, oropharynx and airways. Aggregates of characteristic filamentous virus were present within type I pneumocytes, macrophages, and air spaces of the lung by electron microscopy. Demonstration of fatal aerosol transmission of this virus in monkeys reinforces the importance of taking appropriate precautions to prevent its potential aerosol transmission to humans. Images Figure 3 Figure 4 Figure 5 PMID:7547435

  13. 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.

  14. Pharmacokinetics and disposition of WR-1065 in the rhesus monkey

    SciTech Connect

    Mangold, D.J.; Huelle, B.K.; Miller, M.A.; Geary, R.S.; Sanchez-Barona, D.O.; Swynnerton, N.F.; Fleckenstein, L.; Ludden, T.M. )

    1990-05-01

    The pharmacokinetics of WR-1065 (S-2-(3-aminopropylamino)ethanethiol) were investigated following iv, intraduodenal, and intraportal administrations in the rhesus monkey. Pharmacokinetic parameters were estimated by compartmental modeling of plasma concentration data from 10-min and 120-min iv infusions. Higher apparent volumes of distribution (Vc and Vss) and higher mean residence time (MRT) were observed at the slower infusion rate but a constant total dose. The values reflect a change in the distribution of WR-1065, possibly due to to saturation of binding in plasma and tissue. However, clearance remained unchanged. For a monkey administered approximately twice the 60 mg/kg dose infused over 120 min, data analysis indicates a disproportional increase in AUC and a substantial decrease in clearance. Low and erratic plasma concentrations of free drug (analytically determined without reductive cleavage) were observed following intraduodenal administration of WR-1065, demonstrating the drug's poor oral bioavailability. Results of intraduodenal administrations of radiolabeled drug indicated than an appreciable amount of the radiolabel in the dose reached the systemic circulation. However, after either intraduodenal or iv administration, only 31% of the AUC (radiolabel) could be accounted for as total (free and disulfide-bound) WR-1065 by specific analysis in separate experiments. Low levels of total cysteamine strongly suggest it to be a minor contributor to the disposition of the drug. Free WR-1065 AUC values following intraportal administration were similar to values obtained after iv administration.

  15. 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. PMID:27085798

  16. 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.

  17. Systematic identification and evolutionary features of rhesus monkey small nucleolar RNAs

    PubMed Central

    2010-01-01

    Background Recent studies have demonstrated that non-protein-coding RNAs (npcRNAs/ncRNAs) play important roles during eukaryotic development, species evolution, and in the etiology of disease. Rhesus macaques are the most widely used primate model in both biomedical research and primate evolutionary studies. However, most reports on these animals focus on the functional roles of protein-coding sequences, whereas very little is known about macaque ncRNAs. Results In the present study, we performed the first systematic profiling of intermediate-size ncRNAs (50 to 500 nt) from the rhesus monkey by constructing a cDNA library. We identified 117 rhesus monkey ncRNAs, including 80 small nucleolar RNAs (snoRNAs), 29 other types of known RNAs (snRNAs, Y RNA, and others), and eight unclassified ncRNAs. Comparative genomic analysis and northern blot hybridizations demonstrated that some snoRNAs were lineage- or species-specific. Paralogous sequences were found for most rhesus monkey snoRNAs, the expression of which might be attributable to extensive duplication within the rhesus monkey genome. Further investigation of snoRNA flanking sequences showed that some rhesus monkey snoRNAs are retrogenes derived from L1-mediated integration. Finally, phylogenetic analysis demonstrated that birds and primates share some snoRNAs and host genes thereof, suggesting that both the relevant host genes and the snoRNAs contained therein may be inherited from a common ancestor. However, some rhesus monkey snoRNAs hosted by non-ribosome-related genes appeared after the evolutionary divergence between birds and mammals. Conclusions We provide the first experimentally-derived catalog of rhesus monkey ncRNAs and uncover some interesting genomic and evolutionary features. These findings provide important information for future functional characterization of snoRNAs during primate evolution. PMID:20100322

  18. Cardiac arrhythmias induced by chloral hydrate in rhesus monkeys.

    PubMed

    Han, Pengfei; Song, Haibo; Yang, Pingliang; Xie, Huiqi; Kang, Y James

    2011-06-01

    Chloral hydrate has been long used as a safe sedative and hypnotic drug in humans. However, reports on its cardiovascular adverse effects have been published from time to time. The present study was undertaken to use Rhesus monkeys as a model to define the dose regiment of chloral hydrate at which cardiac arrhythmias can be induced and the consequences of the cardiac events. Male Rhesus monkeys of 2-3 years old were intravenously infused with chloral hydrate starting at 50 mg/kg with an increasing increment of 25 mg/kg until the occurrence of cardiac arrhythmias. In addition, a traditional up-and-down dosing procedure was applied to define a single dose level at which cardiac arrhythmias can be induced. The data obtained showed that when the sequentially escaladed dose reached 125 mg/kg, cardiac arrhythmias occurred in all monkeys tested. The single effective dose to cause cardiac arrhythmias calculated from the crossover analysis was 143 ± 4 mg/kg. This value would be equivalent to 68.6 ± 1.9 mg/kg for children and 46.4 ± 1.3 mg/kg for adults in humans. Under either multiple or single dose condition, cardiac arrhythmias did not occur before 40 min after the onset of anesthesia induced by chloral hydrate. Cardiac arrhythmias were recovered without help at the end of the anesthesia in most cases, but also continued after the regain of consciousness in some cases. The cardiac arrhythmias were accompanied with compromised cardiac function including suppressed fractional shortening and ejection fraction. This study thus suggests that cautions need to be taken when chloral hydrate is used above certain levels and beyond a certain period of anesthesia, and cardiac arrhythmias induced by chloral hydrate need to be closely monitored because compromised cardiac function may occur simultaneously. In addition, patients with cardiac arrhythmias induced by chloral hydrate should be monitored even after they are recovered from the anesthesia.

  19. Complete Genome Sequence of a GII.17 Norovirus Isolated from a Rhesus Monkey in China

    PubMed Central

    Liu, Bo; Tao, Yufen; Li, Chao; Li, Xintong; Liu, Jiansheng; He, Zhanlong; Xia, Ming; Jiang, Xi; Tan, Ming

    2016-01-01

    The previously silent GII.17 norovirus was found to be the predominant genotype causing major epidemics in China in the 2014–2015 winter epidemic season. We report here the complete genomic sequence of a GII.17 norovirus (mky/GII.17/KM1509/CHN/2015) that infected rhesus monkeys at a monkey farm in southwestern China. PMID:27609911

  20. 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…

  1. [Behavioral characteristics of rhesus monkeys in a multiple-choice environment].

    PubMed

    Nikol'skaia, K A; Sagimbaeva, Sh K; Firsov, L A

    1988-01-01

    The present work deals with dynamics of formation of complex alimentary behaviour of rhesus monkeys in multialternative environment. A detailed informational analysis of the obtained results allowed to reveal the properties of processing of proprioceptive information in the course of learning and to understand the characteristics of behaviour of the examined monkeys.

  2. 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…

  3. Complete Genome Sequence of a GII.17 Norovirus Isolated from a Rhesus Monkey in China.

    PubMed

    Liu, Bo; Tao, Yufen; Li, Chao; Li, Xintong; Liu, Jiansheng; He, Zhanlong; Xia, Ming; Jiang, Xi; Tan, Ming; Liu, Hongqi

    2016-01-01

    The previously silent GII.17 norovirus was found to be the predominant genotype causing major epidemics in China in the 2014-2015 winter epidemic season. We report here the complete genomic sequence of a GII.17 norovirus (mky/GII.17/KM1509/CHN/2015) that infected rhesus monkeys at a monkey farm in southwestern China. PMID:27609911

  4. Calcified foci at the junction between adrenal cortex and medulla of rhesus monkeys.

    PubMed

    Kast, A; Peil, H; Weisse, I

    1994-01-01

    The occurrence of calcified foci at the junction of adrenal medulla and cortex in monkeys obtained from toxicity studies during a 10-year period is reported. The survey included reinvestigated adrenal samples from 274 male and 270 female rhesus monkeys and 52 male and 52 female cynomolgus monkeys. The incidence of calcified foci was 46% in male and 45% in female rhesus monkeys, and 6% in male cynomolgus monkeys, while their females did not show the lesion. In male rhesus monkeys, the mean number of foci was 4 for both glands, in females, 2 for the right and 4 for the left one. Initial stages indicated that the lesions develop possibly from focal apoptosis of medulla cells followed by a dystrophic mineralization. No correlation was observed concerning dose groups, test article, study length, testing facility, origin of monkeys, their sex, age, diet or final body weight. The foci of mineralization were dystrophic, species-specific in the rhesus monkey and possibly related to stress. The location of the foci at the cortico-medullary junction, precisely the location of the remnants of the fetal zone, may indicate their origin from this zone.

  5. Interactions between oral contraceptives and malaria infections in rhesus monkeys*

    PubMed Central

    Dutta, G. P.; Puri, S. K.; Kamboj, K. K.; Srivastava, S. K.; Kamboj, V. P.

    1984-01-01

    The interaction of oral contraceptives with malaria infection (Plasmodium cynomolgi B and P. coatneyi) in adult female rhesus monkeys (Macaca mulatta) was studied. The oral contraceptives (Norinyl and Ovral-28) were administered for 12 consecutive menstrual cycles, from day 5 to 25 of each cycle, at either ⅓ of the human dose of Norinyl (norethisterone 0.33 mg + ethinylestradiol 0.012 mg) or ⅙ of the human dose of Ovral-28 (norgestrel 0.083 mg + ethinylestradiol 0.008 mg). The animals were divided into three groups for each infection (control, Norinyl and Ovral-28 treated) with 10 monkeys in each group for P. cynomolgi B infection and 12 in each group for P. coatneyi infection. The animals were infected after 6 cycles of oral contraceptive administration, and the course of infection was studied during the 7th and 8th cycles. This was followed by radical cure during the 9th and 10th cycles and rechallenge in the 11th and 12th cycles. The present study showed that (1) the contraceptive-treated animals maintained a slightly increased cumulative parasite load; (2) the contraceptives did not interfere with the radical curative action of chloroquine; (3) the contraceptive-treated animals showed no significant change in the course of parasitaemia on rechallenge or in the malaria indirect fluorescent antibody levels; (4) the liver function tests were not altered significantly by the administration of contraceptives and subsequent infection; and (5) the haematological changes observed in the contraceptive-treated animals were similar to those observed in the control group. PMID:6335851

  6. Far-field microwave dosimetry in a rhesus monkey model

    SciTech Connect

    Olsen, R.G.; Griner, T.A.; Prettyman, G.D.

    1980-01-01

    Dosimetric measurements were made in a muscle-equivalent model of an adult rhesus monkey subjected to far-field irradiation at 1.29 GHz. Profiles of microwave-induced heating in the model were obtained at eight locations, and a gradient-layer whole-body calorimeter was used to measure total absorbed energy. Average specific absorption rate (SAR) was calculated both from the calorimeter experiments and from the local temperature measurements. Thermographic imaging techniques were used to qualitatively show the microwave-induced surface heating patterns. For this model the calculated average SAR was 0.15 9W/dg)/(mW/cm2) which, at 1.29 GHs, makes the absorption cross section 84% of the geometric shadow cross section. The SAR is about three times that predicted for a prolate spheroidal model of similar mass. A disproportionally high absorption occurred in the legs of the model positioned parallel to the E-polarization because of what is believed to be partial-body resonance.

  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. Psychobiology of early social attachment in rhesus monkeys. Clinical implications.

    PubMed

    Kraemer, G W

    1997-01-15

    "Attachment" has been viewed as the process by which the infant bonds to a caregiver and develops and maintains affiliative social relationships. Whereas past theories suggested that the neurobiological mechanisms that enable the infant to engage in regulated social interactions develop autonomously, the more current view is that the organization of cognitive and emotional systems that regulate social behavior depends on early caregiver-infant attachment. It is well known that disruption of caregiver-infant attachment produces abnormal behavior and increases or decreases the activity of different brain neurochemical systems in rhesus monkeys. Furthermore, it has been suggested that these effects might serve as a model for the etiology of some forms of human psychopathology. Current research indicates that caregiver privation alters the development of usual interrelationships among the activity of several neurochemical and neuroendocrine systems and alters basic cognitive processes. In line with the idea that the caregiver usually exerts a potent organizing effect on the infant's psychobiology, the long-standing effects of caregiver privation on behavior and emotionality are probably attributable to changes in multiple regulatory systems and cognitive-emotional integration rather than restricted effects on the activity of any specific set of neurochemical systems.

  9. Glycoprotein Gene Sequence Variation in Rhesus Monkey Rhadinovirus

    PubMed Central

    Shin, Young C.; Jones, Leandro R.; Manrique, Julieta; Lauer, William; Carville, Angela; Mansfield, Keith G.; Desrosiers, Ronald C.

    2010-01-01

    Gene sequences for seven glycoproteins from 20 independent isolates of rhesus monkey rhadinovirus (RRV) and of the corresponding seven glycoprotein genes from nine strains of the Kaposi’s sarcoma-associated herpesvirus (KSHV) were obtained and analyzed. Phylogenetic analysis revealed two discrete groupings of RRV gH sequences, two discrete groupings of RRV gL sequences and two discrete groupings of RRV gB sequences. We called these phylogenetic groupings gHa, gHb, gLa, gLb, gBa and gBb. gHa was always paired with gLa and gHb was always paired with gLb for any individual RRV isolate. Since gH and gL are known to be interacting partners, these results suggest the need of matching sequence types for function of these cooperating proteins. gB phylogenetic grouping was not associated with gH/gL phylogenetic grouping. Our results demonstrate two distinct, distantly-related phylogenetic groupings of gH and gL of RRV despite a remarkable degree of sequence conservation within each individual phylogenetic group. PMID:20172576

  10. Head Orientation and Handedness Trajectory in Rhesus Monkey Infants (Macaca mulatta)

    PubMed Central

    Nelson, Eliza L.; Emery, Michelle S.; Babcock, Samantha M.; Novak, Matthew F.S.X.; Suomi, Stephen J.; Novak, Melinda A.

    2014-01-01

    In human and chimpanzee infants, neonatal rightward supine head orientation bias predicts later right hand use preference. In an evolutionarily older primate species such as the rhesus monkey, a left hand preference has been reported, but there are no data on head orientation biases. Supine head orientation bias was measured experimentally in 16 rhesus monkey neonates and compared with prone head orientation bias as well as with various measures of hand use preference. A group-level leftward supine head bias was found that corresponded to greater activity in the left hand while supine; however, supine head orientation did not predict later hand preference as measured by reaching or manipulation on a coordinated bimanual task. These data suggest that a trajectory for handedness in rhesus monkeys may be different from that of humans and chimpanzees. PMID:21400487

  11. Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys.

    PubMed

    Barouch, Dan H; Alter, Galit; Broge, Thomas; Linde, Caitlyn; Ackerman, Margaret E; Brown, Eric P; Borducchi, Erica N; Smith, Kaitlin M; Nkolola, Joseph P; Liu, Jinyan; Shields, Jennifer; Parenteau, Lily; Whitney, James B; Abbink, Peter; Ng'ang'a, David M; Seaman, Michael S; Lavine, Christy L; Perry, James R; Li, Wenjun; Colantonio, Arnaud D; Lewis, Mark G; Chen, Bing; Wenschuh, Holger; Reimer, Ulf; Piatak, Michael; Lifson, Jeffrey D; Handley, Scott A; Virgin, Herbert W; Koutsoukos, Marguerite; Lorin, Clarisse; Voss, Gerald; Weijtens, Mo; Pau, Maria G; Schuitemaker, Hanneke

    2015-07-17

    Preclinical studies of viral vector-based HIV-1 vaccine candidates have previously shown partial protection against neutralization-resistant virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by purified envelope (Env) glycoprotein boosting. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env, Gag, and Pol and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repeated, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repeated, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of neutralization-resistant virus challenges in rhesus monkeys. PMID:26138104

  12. Protective Efficacy of Adenovirus/Protein Vaccines Against SIV Challenges in Rhesus Monkeys

    PubMed Central

    Barouch, Dan H.; Alter, Galit; Broge, Thomas; Linde, Caitlyn; Ackerman, Margaret E.; Brown, Eric P.; Borducchi, Erica N.; Smith, Kaitlin M.; Nkolola, Joseph P.; Liu, Jinyan; Shields, Jennifer; Parenteau, Lily; Whitney, James B.; Abbink, Peter; Ng’ang’a, David M.; Seaman, Michael S.; Lavine, Christy L.; Perry, James R.; Li, Wenjun; Colantonio, Arnaud D.; Lewis, Mark G.; Chen, Bing; Wenschuh, Holger; Reimer, Ulf; Piatak, Michael; Lifson, Jeffrey D.; Handley, Scott A.; Virgin, Herbert W.; Koutsoukos, Marguerite; Lorin, Clarisse; Voss, Gerald; Weijtens, Mo; Pau, Maria G.; Schuitemaker, Hanneke

    2015-01-01

    Preclinical studies of viral vector-based HIV-1 vaccine candidates have previously shown partial protection against stringent virus challenges in rhesus monkeys. In this study, we evaluated the protective efficacy of adenovirus serotype 26 (Ad26) vector priming followed by boosting with a purified envelope (Env) glycoprotein. Rhesus monkeys primed with Ad26 vectors expressing SIVsmE543 Env/Gag/Pol antigens and boosted with AS01B-adjuvanted SIVmac32H Env gp140 demonstrated complete protection in 50% of vaccinated animals against a series of repetitive, heterologous, intrarectal SIVmac251 challenges that infected all controls. Protective efficacy correlated with the functionality of Env-specific antibody responses. Comparable protection was also observed with a similar Ad/Env vaccine against repetitive, heterologous, intrarectal SHIV-SF162P3 challenges. These data demonstrate robust protection by Ad/Env vaccines against acquisition of stringent virus challenges in rhesus monkeys. PMID:26138104

  13. Thyroid status of female rhesus monkeys and preliminary information on impact of perchlorate administration.

    PubMed

    Ozpinar, Aysel; Golub, Mari S; Poppenga, Robert H; Blount, Benjamin C; Gillespie, Jerry R

    2011-07-01

    Thyroid status was assessed in adult female rhesus monkey breeders at the California National Primate Research Center at the beginning of the breeding season. The 95% confidence intervals for thyrotropin (TSH), thyroxine (T(4)) and triiodothyronine (T(3)) (n = 66-80) were similar to those previously reported in smaller samples of macaque monkeys. Based on human criteria, 10 of 80 monkeys (12%) were hypothyroid (TSH > 2.0 µIU/mL). Because hypothyroxinaemia can be a risk factor in pregnancy, T(4) status was compared with past breeding history, breeding outcome for that season and general health records in a subset of 42 breeders. Age, weight and parity did not differ between monkeys in the lowest T(4) quartile as compared with those in the upper three quartiles. However, T(4) concentrations were significantly associated with the number of missed menstrual cycles during the previous breeding season. In additional work, three healthy lactating rhesus monkeys were given three different doses of environmental contaminant and thyroid iodine uptake inhibitor, ammonium perchlorate (0.006, 0.34, 12.8 mg/kg/day, respectively) in food for two weeks. Thyroid status variables (TSH, T(4), T(3), thyroid radioactive iodine uptake) were then measured. In the monkey receiving the highest perchlorate dose, iodine uptake was suppressed relative to baseline. The study shows the availability of tools to study thyroid status in rhesus monkeys, the variability of thyroid status in the breeder colony and the potential ability of environmental factors to influence thyroid status.

  14. 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.

  15. Tissue tropism of simian immunodeficiency virus in rhesus monkeys

    SciTech Connect

    Wyand, M.S.

    1989-01-01

    Simian immunodeficiency virus (SIV) is a T-lymphotropic lentivirus that is genetically, immunologically, and morphologically related to the human immunodeficiency viruses type 1 and 2 (HIV-1, HIV-2). In rhesus monkeys, SIV induces a progressively fatal immunodeficiency syndrome strikingly similar to human acquired immunodeficiency syndrome (AIDS). The tissue and cellular tropism of SIV was determined by immunocytochemistry and in situ hybridization using a 3.48 kilobase SIV envelope gene probe labeled with biotin, {sup 35}S, or {sup 3}H. Probes labeled with {sup 35}S nonspecifically bound to tissue eosinophils and produced poor signal resolution compared to tritium labeled probes. Biotin labeled probes did not detect SIV under similar hybridization conditions. Formalin-fixed, paraffin-embedded tissues produced strong hybridization signal with superior morphology compared to frozen tissues. Gastrointestinal, respiratory, and lymphoid tissues most frequently contained SIV RNA. The distribution of SIV did not correlate with sex, or viral inoculum, but was most extensive in animals with SIV induced granulomatous encephalitis. SIV was most frequently observed in lymphocytes and macrophages. In the brain focal granulomas were composed almost entirely of EBM11+, lysozyme+, macrophages which contained large amounts of SIV RNA and p27 core protein detected by the monoclonal antibody R1C7. Cells away from granulomas in the brain parenchyma and around blood vessels contained virus and were compatible with oligodendrocytes and astrocytes. Lymph nodes in follicular hyperplasia contained small numbers of SIV positive cells compatible with lymphocytes in the paracortex and mantle zones as well as in cells of the germinal center. Lymph nodes in various stages of follicular depletion with expanded paracortices contained large numbers of cells with SIV RNA in lymphocytes and macrophages.

  16. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

    PubMed

    Abbink, Peter; Larocca, Rafael A; De La Barrera, Rafael A; Bricault, Christine A; Moseley, Edward T; Boyd, Michael; Kirilova, Marinela; Li, Zhenfeng; Ng'ang'a, David; Nanayakkara, Ovini; Nityanandam, Ramya; Mercado, Noe B; Borducchi, Erica N; Agarwal, Arshi; Brinkman, Amanda L; Cabral, Crystal; Chandrashekar, Abishek; Giglio, Patricia B; Jetton, David; Jimenez, Jessica; Lee, Benjamin C; Mojta, Shanell; Molloy, Katherine; Shetty, Mayuri; Neubauer, George H; Stephenson, Kathryn E; Peron, Jean Pierre S; Zanotto, Paolo M de A; Misamore, Johnathan; Finneyfrock, Brad; Lewis, Mark G; Alter, Galit; Modjarrad, Kayvon; Jarman, Richard G; Eckels, Kenneth H; Michael, Nelson L; Thomas, Stephen J; Barouch, Dan H

    2016-09-01

    Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans. PMID:27492477

  17. Protective efficacy of multiple vaccine platforms against Zika virus challenge in rhesus monkeys.

    PubMed

    Abbink, Peter; Larocca, Rafael A; De La Barrera, Rafael A; Bricault, Christine A; Moseley, Edward T; Boyd, Michael; Kirilova, Marinela; Li, Zhenfeng; Ng'ang'a, David; Nanayakkara, Ovini; Nityanandam, Ramya; Mercado, Noe B; Borducchi, Erica N; Agarwal, Arshi; Brinkman, Amanda L; Cabral, Crystal; Chandrashekar, Abishek; Giglio, Patricia B; Jetton, David; Jimenez, Jessica; Lee, Benjamin C; Mojta, Shanell; Molloy, Katherine; Shetty, Mayuri; Neubauer, George H; Stephenson, Kathryn E; Peron, Jean Pierre S; Zanotto, Paolo M de A; Misamore, Johnathan; Finneyfrock, Brad; Lewis, Mark G; Alter, Galit; Modjarrad, Kayvon; Jarman, Richard G; Eckels, Kenneth H; Michael, Nelson L; Thomas, Stephen J; Barouch, Dan H

    2016-09-01

    Zika virus (ZIKV) is responsible for a major ongoing epidemic in the Americas and has been causally associated with fetal microcephaly. The development of a safe and effective ZIKV vaccine is therefore an urgent global health priority. Here we demonstrate that three different vaccine platforms protect against ZIKV challenge in rhesus monkeys. A purified inactivated virus vaccine induced ZIKV-specific neutralizing antibodies and completely protected monkeys against ZIKV strains from both Brazil and Puerto Rico. Purified immunoglobulin from vaccinated monkeys also conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector vaccine, both expressing ZIKV premembrane and envelope, also elicited neutralizing antibodies and completely protected monkeys against ZIKV challenge. These data support the rapid clinical development of ZIKV vaccines for humans.

  18. 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.

  19. 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.

  20. 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.

  1. Conjugated and unconjugated bilirubins in bile of humans and rhesus monkeys. Structure of adult human and rhesus-monkey bilirubins compared with dog bilirubins.

    PubMed Central

    Blumenthal, S G; Taggart, D B; Ikeda, R; Ruebner, B; Bergstrom, D E

    1977-01-01

    1. Bilirubin-IXalpha, -IXalpha diglucuronide, -IXalpha monoglucuronide, -IXalpha monoglucoside -IXalpha monoxyloside, a bilirubin-IXalpha diconjugate containing glucose and another unknown compound, and bilirubin-IXbeta are present in gall-bladder bile of adult human, rhesus monkey and dog. Dog bile normally also contains other bilirubin-IXalpha diconjugates, i.e. compounds containing two conjugating sugars such as glucuronic acid and glucose, glucuronic acid and xylose and glucose xylose. 2. Azopigments alphaF, alphaO, alpha2, alpha3, betax and delta derived from human and rhesus-monkey bilirubins are identical in their chemical composition with those obtained from the dog. 3. Azopigments alphaF and betax found in diazotized biles of adult humans, rhesus monkeys and dogs are products of unconjugated bilirubin-IXbeta. 4. Technical modifications of previously published procedures [Heirwegh, Fevery, Michiels, Van Hees & Compernolle, (1975) Biochem. J. 145, 185-199] were introduced which make it possible to separate the bilirubins, diazotize the separated bilirubins, extract the azopigments and chromatograph them in one working day (6-8h). Images Fig. 1. Fig. 2. PMID:414741

  2. 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…

  3. 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…

  4. Acquisition of Cocaine Self-Administration with Unsignaled Delayed Reinforcement in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Galuska, Chad M.; Woods, James H.

    2005-01-01

    Six experimentally naive rhesus monkeys produced 0.01 mg/kg/infusion cocaine by lever pressing under a tandem fixed-ratio 1 differential-reinforcement-of-other- behavior schedule. One lever press initiated an unsignaled 15- or 30-s delay culminating in cocaine delivery. Each press made during the delay reset the delay interval. With two…

  5. 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…

  6. Influence of Social Variables on the Biobehavioral Response to Separation in Rhesus Monkey Infants.

    ERIC Educational Resources Information Center

    Levine, Seymour; And Others

    1984-01-01

    Four-month-old rhesus monkeys were removed from their social group under three different conditions of perceptual isolation from their mothers and peers. Infant behavior was recorded and blood samples were obtained for analysis of plasma cortisol. Infants never showed signs of depression; their responses following separation were seen as attempts…

  7. 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…

  8. 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…

  9. Mother-Infant Interaction in Rhesus Monkeys Treated Chronically with Delta-9-Tetrahydrocannabinol.

    ERIC Educational Resources Information Center

    Golub, Mari S.; And Others

    1981-01-01

    Drug-exposed mother-infant rhesus monkey pairs were similar to nontreated controls in the amount and types of activity displayed at the infant's tenth and ninetieth day of age. At about 3 months of age drug-exposed pairs increased in interaction, signaling mother-infant independence. This finding suggests that mother-infant attachment may be…

  10. 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…

  11. 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.

  12. Reproductive consequences of a matrilineal overthrow in rhesus monkeys

    PubMed Central

    Dettmer, Amanda M.; Woodward, Ruth A.; Suomi, Stephen J.

    2014-01-01

    Matrilineal overthrows in macaque societies are rare but devastating events, often resulting in severe morbidity, mortality, and loss of individual and group fitness. The handful of documented macaque overthrows provides scant evidence to reveal the severity or longevity of reproductive consequences resulting from such violent events. We analyzed archival records from semi-free ranging rhesus monkeys, Macaca mulatta, across six years [55≤N≤107, from 2007–2012] during which time a matrilineal overthrow occurred [in 2009] to test the hypothesis that extremely violent interactions such as a matrilineal overthrow would significantly reduce reproductive fitness for the involved matrilines and for the troop collectively. The matrilineal overthrow resulted in a significant increase in infant loss for the population from the previous year [χ2=8.117, df=1, P=0.004], as evidenced by the fact that in 2009, but not in other years, the proportion of infants lost was greater than the proportion of viable infants [χ2=4.55, df=1, P=0.03]. Moreover, the deposed matriline suffered 100% infant loss in 2009, a significant change from the previous year [χ2=7.87, df=1, P=0.005] while the attacking matriline suffered 50% infant loss [also a significant change from the previous year; χ2=4.44, df=1, P=0.035], with the uninvolved, lowest-ranking matriline showing no change in infant loss from the previous year [χ2=0.008, df=1, P=0.93]. The deposed matriline did not produce viable offspring again until three years later. We further found that rates of severe fighting [as indicated by the number of fight wounds requiring medical treatment] were positively correlated with infant loss across the six years of the study [r[s]=0.943, P=0.005]. Our data indicate that extreme periods of intra-group conflict, such as the matrilineal overthrow, have marked short-term consequences for individual fitness, and may be extreme examples of the long-term influences that group violence exerts on

  13. Rhesus Monkeys (Macaca mulatta) Detect Rhythmic Groups in Music, but Not the Beat

    PubMed Central

    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). PMID:23251509

  14. 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). PMID:23251509

  15. 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).

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

    SciTech Connect

    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.

    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 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. Finally, future research areas are identified that would either allow replacing assumptions or improving the newly developed lung model.

  17. Effects of feeding selenium deficient diets to rhesus monkeys (Macaca Mulatta)

    SciTech Connect

    Butler, J.A.; Whanger, P.D.; Patton, N.M.

    1988-02-01

    Pregnant rhesus monkeys (Macaca mulatta) were fed either selenium (Se) deficient or Se supplemented diets with adequate vitamin E. Except for some cardiac irregularities in the first babies born to these females, no physiological disorders due to Se deficiency were seen in a subsequent offspring. Plasma and erythrocyte glutathione peroxidase activities and blood Se levels increased in the Se supplemented monkeys but decreased in the deficient ones. The data indicated that hair Se levels reflect long term exposure to this element. In a very preliminary experiment, evidence was obtained to indicate that dietary protein deficiency along with Se deficiency will generate cardiomyopathic lesions characteristic of Se deficiency. It is hypothesized that, in addition to Se deficiency, another dietary deficiency (or abnormality) is necessary to produce Se deficiency lesions in higher primates. Higher glutathione transferase (or non-Se glutathione peroxidase) activity in tissues of rhesus monkeys may account for this resistance.

  18. Indirect immunofluorescence, serum neutralization, and viremia responses of rhesus monkeys (Macaca mulatta) to Machupo virus.

    PubMed

    Gonder, E; Eddy, G

    1986-06-01

    Although indirect immunofluorescent antibody tests (IFAT) have been developed for several arenaviruses, none has been applied to the rhesus monkey model for Bolivian hemorrhagic fever (caused by the arenavirus Machupo). We infected eight rhesus monkeys with Machupo virus and bled them weekly for determination of viremia and for serum antibody detection by IFAT and serum neutralization (SN) testing. Viremia peaked day 14 post-inoculation (PI), when two of eight animals had low IFAT titers. At day 21 PI, the six surviving monkeys had elevated IFAT titers and diminished viremias. SN titers were not observed until 28 days PI, when three of four survivors had low titers. Results of the IFAT were available more rapidly than the SN, and detected increased serum antibody titers earlier than the SN. Acetone fixation did not completely inactivate BHF antigen spot slides.

  19. Long-term marginal zinc deprivation in rhesus monkeys. IV. Effects on skeletal growth and mineralization.

    PubMed

    Leek, J C; Keen, C L; Vogler, J B; Golub, M S; Hurley, L S; Hendrickx, A G; Gershwin, M E

    1988-05-01

    Skeletal maturation was evaluated from ages 1 to 3 y in rhesus monkeys that had been subjected to a diet marginally deficient in zinc (4 micrograms/g Zn) from conception through age 3 y. Skeletal development was assessed at 18, 24, 30, and 36 mo of age and compared with that of controls fed ad libitum. Skeletal maturation was determined by the presence of epiphyseal ossification centers. To evaluate endochondral bone mineralization the appearance of the zone of provisional calcification on the metaphyseal side of the growth plate and the width of the growth plate were observed. Marginal Zn deprivation was associated with delayed skeletal maturation in monkeys up to age 3 y. Defective mineralization of bone was evident in these monkeys up to age 6 mo. Between ages 6 mo and 3 y bone mineralization increased in some of the marginal-Zn monkeys to values that were only slightly below those for control monkeys.

  20. Behavioral efficacy of diazepam against nerve agent exposure in rhesus monkeys. (Reannouncement with new availability information)

    SciTech Connect

    Castro, C.A.; Larsen, T.; Finger, A.V.; Solana, R.P.; McMaster, S.B.

    1991-12-31

    The possibility that nerve agents will be used on the battlefield is real. The traditional therapy against nerve agent exposure consists of pyridostigmine pretreatment and atropine-pralidoxime chloride therapy administered after nerve agent exposure. This therapy regimen is extremely effective in preventing mortality in laboratory animals exposed to multilethal concentrations of nerve agent, yet these animals often display convulsions, brain damage, and behavioral incapacitation. We report here that the addition of diazepam to the traditional therapy for nerve agent (soman) exposure not only decreases the incidence of convulsions, but also attenuates the cognitive impairments of rhesus monkeys trained on a Serial Probe Recognition (SPR) task. Monkeys which received diazepam treatment required only 6 days before their performance on the SPR task returned to presoman exposure levels, compared to nondiazepamtreated monkeys which required 15 days. Moreover, only 1 out of the 5 monkeys which received diazepain treatment suffered tonic-clonic convulsions; in contrast all 5 monkeys which did not receive diazepam treatment experienced severe convulsive episodes. These results suggest that diazepam would be an excellent adjunct to traditional nerve agent therapy to facilitate behavioral recovery from nerve agent intoxication that might be encountered by US military personnel on the battlefield or accidental organophosphate poisoning encountered in industrial or agricultural accidents. Serial probe recognition task, diazepam, nerve agents, soman convulsions, rhesus monkeys, cognition, organophosphate.

  1. Thyroid status of female rhesus monkeys and preliminary information on impact of perchlorate administration.

    PubMed

    Ozpinar, Aysel; Golub, Mari S; Poppenga, Robert H; Blount, Benjamin C; Gillespie, Jerry R

    2011-07-01

    Thyroid status was assessed in adult female rhesus monkey breeders at the California National Primate Research Center at the beginning of the breeding season. The 95% confidence intervals for thyrotropin (TSH), thyroxine (T(4)) and triiodothyronine (T(3)) (n = 66-80) were similar to those previously reported in smaller samples of macaque monkeys. Based on human criteria, 10 of 80 monkeys (12%) were hypothyroid (TSH > 2.0 µIU/mL). Because hypothyroxinaemia can be a risk factor in pregnancy, T(4) status was compared with past breeding history, breeding outcome for that season and general health records in a subset of 42 breeders. Age, weight and parity did not differ between monkeys in the lowest T(4) quartile as compared with those in the upper three quartiles. However, T(4) concentrations were significantly associated with the number of missed menstrual cycles during the previous breeding season. In additional work, three healthy lactating rhesus monkeys were given three different doses of environmental contaminant and thyroid iodine uptake inhibitor, ammonium perchlorate (0.006, 0.34, 12.8 mg/kg/day, respectively) in food for two weeks. Thyroid status variables (TSH, T(4), T(3), thyroid radioactive iodine uptake) were then measured. In the monkey receiving the highest perchlorate dose, iodine uptake was suppressed relative to baseline. The study shows the availability of tools to study thyroid status in rhesus monkeys, the variability of thyroid status in the breeder colony and the potential ability of environmental factors to influence thyroid status. PMID:21669905

  2. Planar relationships of the semicircular canals in rhesus and squirrel monkeys.

    PubMed

    Blanks, R H; Curthoys, I S; Bennett, M L; Markham, C H

    1985-08-12

    The technique of principal-component analysis was used to define anatomically the semicircular canal planes of the rhesus and squirrel monkeys with respect to the stereotaxic coordinate system. The analyses were performed on a series of points obtained from the dissected osseous labyrinths. A planar equation was defined for each canal plane in the stereotaxic coordinate system and angles were calculated between the 3 ipsilateral canal planes, between synergistic canal pairs and between each canal plane and the stereotaxic planes. The data from both species are similar: the ipsilateral canal planes are nearly orthogonal; synergistic pairs of canal planes are approximately parallel with angles of 2 degrees-12 degrees between pairs in the rhesus monkey and 13 degrees-16 degrees between pairs in the squirrel monkey. The horizontal canal planes form angles of 22 degrees and 18 degrees with the horizontal stereotaxic plane in the rhesus and squirrel monkeys, respectively. A head position of 15 degrees (pitch nose-down) was calculated to produce an optimal head position in both species for maximally stimulating the horizontal canals and minimally stimulating the vertical canals during horizontal angular acceleration. The radii of curvature (R) of the horizontal, anterior and posterior canals were also measured for both species using a calibrated reticle. These measurements indicate that the anterior canal of both species has the largest radius of curvature. This anatomical information is discussed in relation to the available physiological data. PMID:3896405

  3. Metabolic and vasomotor responses of rhesus monkeys exposed to 225-MHz radiofrequency energy

    SciTech Connect

    Lotz, W.G.; Saxton, J.L.

    1987-01-01

    A previous study showed a substantial increase in the colonic temperature of rhesus monkeys (Macaca mulatta) exposed to radio-frequency (RF) fields at a frequency near whole-body resonance and specific absorption rates (SAR) of 2 to 3 W/kg. The present experiments were conducted to determine the metabolic and vasomotor responses during exposures to similar RF fields. Five adult male rhesus monkeys were exposed to 225-MHz radiation (E orientation) in an anechoic chamber. The monkeys were irradiated at two carefully-controlled ambient temperatures, either cool (20 C) or thermoneutral (26 C). Power densities ranged from 0 (sham) to 10.0 mW/sq cm with an average whole-body SAR of 0.285 (W/kg)/(mW/sq cm). Two experimental protocols were used, each of which began with a 120-min preexposure equilibration period. Then, one protocol involved repetitive 10-min RF exposures at successively higher power densities with a recovery period between exposures. In the second protocol, a 120-min RF exposure permitted the measurement of steady-state thermoregulatory responses. Metabolic and vasomotor adjustments in the rhesus monkey exposed to 225 MHz occurred during brief or sustained exposures at SARs at or above 1.4 W/kg. Metabolic and vasomotor responses were coordinated effectively to produce a stable deep-body temperature. The results show that the thermoregulatory response of the rhesus monkey to an RF exposure at a resonant frequency limits storage of heat in the body. However, substantial increases in colonic temperature were not prevented by such responses, even in a cool environment.

  4. Metabolic and vasomotor responses of rhesus monkeys exposed to 225-MHz radiofrequency energy. [Macaca mulatta

    SciTech Connect

    Lotz, W.G.; Saxton, J.L.

    1987-01-01

    A previous study showed a substantial increase in the colonic temperature of rhesus monkeys (Macaca mulatta) exposed to radiofrequency (RF) fields at a frequency near whole-body resonance and specific absorption rates (SAR) of 2-3 W/kg. The present experiments were conducted to determine the metabolic and vasomotor responses during exposures to similar RF fields. We exposed five adult male rhesus monkeys to 225 MHz radiation (E orientation) in an anechoic chamber. Oxygen consumption and carbon dioxide production were measured before, during, and after RF exposure. Colonic, tail and leg skin temperatures were continuously monitored with RF-nonperturbing probes. The monkeys were irradiated at two carefully-controlled ambient temperatures, either cool (20 degrees C) or thermoneutral (26 degrees C). Power densities ranged from 0 (sham) to 10.0 mW/cm2 with an average whole-body SAR of 0.285 (W/kg)/(mW/cm2). We used two experimental protocols, each of which began with a 120-min pre-exposure equilibration period. One protocol involved repetitive 10-min RF exposures at successively higher power densities with a recovery period between exposures. In the second protocol, a 120-min RF exposure permitted the measurement of steady-state thermoregulatory responses. Metabolic and vasomotor adjustments in the rhesus monkey exposed to 225 MHz occurred during brief or sustained exposures at SARs at or above 1.4 W/kg. The SAR required to produce a given response varied with ambient temperature. Metabolic and vasomotor responses were coordinated effectively to produce a stable deep body temperature. The results show that the thermoregulatory response of the rhesus monkey to an RF exposure at a resonant frequency limits storage of heat in the body. However, substantial increases in colonic temperature were not prevented by such responses, even in a cool environment.

  5. Soluble human CD4 elicits an antibody response in rhesus monkeys that inhibits simian immunodeficiency virus replication

    SciTech Connect

    Watanabe, Mamoru; Chen, Zheng W.; Tsubota, Hiroshi; Lord, C.I.; Levine, C.G.; Letvin, N.L. )

    1991-01-01

    Rhesus monkeys infected with the simian immunodeficiency virus of macaques (SIV{sub mac}) demonstrate significant virologic and clinical improvement as a result of treatment with human recombinant soluble CD4 (rsCD4). The authors show that human rsCD4 does not efficiently inhibit SIV{sub mac} replication in bone marrow macrophages of rhesus monkeys and does not significantly augment bone marrow hematopoietic colony formation in vitro. However, plasma of human rsCD4-treated rhesus monkeys does exhibit significant anti-SIV{sub mac} activity in vitro. Plasma of these animals efficiently blocks SIV{sub mac} replicaton in peripheral blood lymphocytes and bone marrow macrophages. It also increases granulocyte/macrophage colony formation in vitro by bone marrow cells of SIV{sub mac}-infected monkeys. This plasma and the IgG fraction of plasma from a rhesus monkey immunized with human rsCD4 in adjuvant demonstrate reactivity with a soluble form of the rhesus monkey CD4 molecule, exhibit binding to CD4{sup +} but not CD8{sup +} concanavalin A-activated rhesus monkey peripheral blood lymphocytes, and precipitate the CD4 molecule from surface-labeled activated rhesus monkey peripheral blood lymphocytes. Moreover, anti-viral activity is demonstrable in the IgG fraction of plasma from a human rsCD4-immunized monkey. These studies raise the possibility that a modified human CD4 molecule serving as an immunogen might elicit an antibody response that could potentially induce a beneficial therapeutic response in human immunodeficiency virus-infected individuals.

  6. Spectral sensitivity differences between rhesus monkeys and humans: implications for neurophysiology

    PubMed Central

    Lindbloom-Brown, Zachary; Tait, Leah J.

    2014-01-01

    Spectral sensitivity of humans and rhesus monkeys was compared using identical displays and similar procedures. Detection thresholds were measured for the following: 1) 15-Hz modulation of a blue and a green cathode-ray tube phosphor; 2) 15-Hz modulation of all three phosphors together; and 3) slow (<1 Hz) modulations of a blue and a green phosphor under scotopic conditions. Monkeys had lower blue-to-green threshold ratios than humans at all eccentricities tested (0.5 to 7°), consistent with a lower lens optical density in monkeys. In addition to apparently having a lower lens density than humans, monkeys were more sensitive to 15-Hz red-green isoluminant modulations than humans, an effect that cannot be explained by optical factors. PMID:25253473

  7. Challenges to Maternal Wellbeing during Pregnancy Impact Temperament, Attention, and Neuromotor Responses in the Infant Rhesus Monkey

    PubMed Central

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

    2011-01-01

    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. PMID:20882585

  8. Simian virus 40-induced disease in rhesus monkeys with simian acquired immunodeficiency syndrome.

    PubMed Central

    Horvath, C. J.; Simon, M. A.; Bergsagel, D. J.; Pauley, D. R.; King, N. W.; Garcea, R. L.; Ringler, D. J.

    1992-01-01

    Simian virus 40 (SV40) disease was diagnosed in four rhesus monkeys that died with SIV-induced acquired immunodeficiency syndrome (AIDS). One juvenile monkey seroconverted for SV40 6 months after inoculation with SIV and developed severe bilateral tubulointerstitial nephritis. In contrast, progressive multifocal leukoencephalopathy (PML) occurred in two adult monkeys that were seropositive for SV40 before SIV inoculation, as well as a third adult that was naturally infected with SIV and seropositive for SV40 5 years before death. Large intranuclear inclusions containing abundant polyomavirus particles were limited to either renal tubular epithelial cells or oligodendrocytes. In situ DNA hybridization for SV40 large T antigen further demonstrated that SV40 nucleic acid was localized to either kidney or brain tissue. By immunohistochemical analysis, areas of central nervous system inflammation and demyelination were shown to contain CD68+ macrophages (gitter cells), aggregates of CD8+ T lymphocytes, and numerous gemistocytic astrocytes that labeled for glial fibrillary acidic protein. These observations indicate that rhesus monkeys with SIV-induced AIDS are predisposed to polyomaviral disease, in which SV40 nucleic acid is observed in renal tissue in primary infections and brain tissue after viral reactivation. Furthermore, this organ-specific replication suggests that tissue-tropic strains of SV40 may develop in immunodeficient monkeys. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:1376560

  9. Effect of prolonged ketamine exposure on cardiovascular physiology in pregnant and infant rhesus monkeys (Macaca mulatta).

    PubMed

    Hotchkiss, Charlotte E; Wang, Cheng; Slikker, William

    2007-11-01

    Physiologic measurements in nonhuman primates usually are collected from animals that are chemically or physically restrained. Both types of restraint may affect the parameters measured, and those effects can vary with age. Heart rate, respiratory rate, oxygen saturation, expired CO2, blood pressure, temperature, blood glucose, hematocrit, and venous blood gasses were measured in rhesus monkeys that were either infused intravenously with ketamine for 24 h or were cage-housed and physically restrained for sample collection. The subjects were pregnant monkeys at gestational day 120 to 123, infants 5 to 6 d old, and infants 35 to 37 d old. Heart rate and blood pressure were lower in ketamine-treated monkeys than physically restrained monkeys. Heart rate was higher in infants than adults, whereas blood pressure was lower in infants. Respiratory rate was higher in infants than adults and higher in physically restrained infants than ketamine-sedated infants but was not affected by ketamine in pregnant adults. Hematocrit was decreased in older infants. In summary, both physical restraint and ketamine sedation altered several physiologic parameters in pregnant and infant rhesus macaques. Investigators should consider these effects when designing experiments and evaluating experimental outcomes in monkeys.

  10. 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.

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

    SciTech Connect

    Loo, J.C.K.; Tryphonas, H.; Jordan, N.; Brien, R.; Karpinski, K.R.; Arnold, D.L. )

    1989-11-01

    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.

  12. 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.

  13. Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys

    PubMed Central

    Maestripieri, Dario

    2005-01-01

    Maternal abuse of offspring in macaque monkeys shares some similarities with child maltreatment in humans, including its transmission across generations. This study used a longitudinal design and a cross-fostering experiment to investigate whether abusive parenting in rhesus macaques is transmitted from mothers to daughters and whether transmission occurs through genetic or experiential factors. Nine of 16 females who were abused by their mothers in their first month of life, regardless of whether they were reared by their biological mothers or by foster mothers, exhibited abusive parenting with their firstborn offspring, whereas none of the females reared by nonabusive mothers did. These results suggest that the intergenerational transmission of infant abuse in rhesus monkeys is the result of early experience and not genetic inheritance. The extent to which the effects of early experience on the intergenerational transmission of abusive parenting are mediated by social learning or experience-induced physiological alterations remains to be established. PMID:15983367

  14. 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

  15. Lipofuscin in retinal pigment epithelium of rhesus monkey: lack of diminution with centrophenoxine treatment.

    PubMed

    Andrews, L D; Brizzee, K R

    1986-01-01

    An experiment was performed to test the ability of Centrophenoxine to reduce the amount of lipofuscin (age pigment) in the retinal pigment epithelium (RPE) of aged rhesus monkeys. Centrophenoxine is reputed to have this action in neurons of lower mammals. Quantitative electron microscopic analysis was performed on sections from the perifovea of ten rhesus monkeys, all approximately 20 years of age. Four of the animals received 80 mg/kg Centrophenoxine (IM injection) daily for 12 weeks. No significant difference between the treated and control groups could be demonstrated statistically (Mann-Whitney U-test) either in the fraction of RPE cell cytoplasm occupied by lipofuscin granules or in the average size of the granules.

  16. Early experience affects the intergenerational transmission of infant abuse in rhesus monkeys.

    PubMed

    Maestripieri, Dario

    2005-07-01

    Maternal abuse of offspring in macaque monkeys shares some similarities with child maltreatment in humans, including its transmission across generations. This study used a longitudinal design and a cross-fostering experiment to investigate whether abusive parenting in rhesus macaques is transmitted from mothers to daughters and whether transmission occurs through genetic or experiential factors. Nine of 16 females who were abused by their mothers in their first month of life, regardless of whether they were reared by their biological mothers or by foster mothers, exhibited abusive parenting with their firstborn offspring, whereas none of the females reared by nonabusive mothers did. These results suggest that the intergenerational transmission of infant abuse in rhesus monkeys is the result of early experience and not genetic inheritance. The extent to which the effects of early experience on the intergenerational transmission of abusive parenting are mediated by social learning or experience-induced physiological alterations remains to be established.

  17. 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

  18. Control of working memory in rhesus monkeys (Macaca mulatta).

    PubMed

    Tu, Hsiao-Wei; Hampton, Robert R

    2014-10-01

    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, whereas discrimination accuracy was equivalent in the 2 cue conditions. We also tested monkeys with lists of 2 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:25546104

  19. 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…

  20. Elasticity and stress relaxation of rhesus monkey (Macaca mulatta) vocal folds

    PubMed Central

    Riede, Tobias

    2010-01-01

    Fundamental frequency is an important perceptual parameter for acoustic communication in mammals. It is determined by vocal fold oscillation, which depends on the morphology and viscoelastic properties of the oscillating tissue. In this study, I tested if stress–strain and stress–relaxation behavior of rhesus monkey (Macaca mulatta) vocal folds allows the prediction of a species' natural fundamental frequency range across its entire vocal repertoire as well as of frequency contours within a single call type. In tensile tests, the load–strain and stress–relaxation behavior of rhesus monkey vocal folds and ventricular folds has been examined. Using the string model, predictions about the species' fundamental frequency range, individual variability, as well as the frequency contour of ‘coo’ calls were made. The low- and mid-frequency range (up to 2 kHz) of rhesus monkeys can be predicted relatively well with the string model. The discrepancy between predicted maximum fundamental frequency and what has been recorded in rhesus monkeys is currently ascribed to the difficulty in predicting the behavior of the lamina propria at very high strain. Histological sections of the vocal fold and different staining techniques identified collagen, elastin, hyaluronan and, surprisingly, fat cells as components of the lamina propria. The distribution of all four components is not uniform, suggesting that different aspects of the lamina propria are drawn into oscillation depending on vocal fold tension. A differentiated recruitment of tissue into oscillation could extend the frequency range specifically at the upper end of the frequency scale. PMID:20709920

  1. A 75-year pictorial history of the Cayo Santiago rhesus monkey colony.

    PubMed

    Kessler, Matthew J; Rawlins, Richard G

    2016-01-01

    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.

  2. Can free-ranging rhesus monkeys (Macaca mulatta) extract artificially created rules comprised of natural vocalizations?

    PubMed

    Hauser, Marc David; Glynn, David

    2009-05-01

    Though nonhuman animals lack anything like a set of grammatical structures in their natural vocalizations, studies now suggest that at least some animals can extract patterns from a structured input that appear abstract and rule-like. The authors continue this line of research by adding three new methodological contributions, specifically, tests of (1) a free-ranging animal population (as opposed to captive laboratory subjects), (2) a new taxonomic group (i.e., Old World monkeys: rhesus macaques, Macaca mulatta), and (3), the presentation of artificially sequenced strings of species-specific vocalizations (as opposed to artificial symbols or speech stimuli). Specifically, the authors created artificial strings of rhesus vocalizations in the pattern notated as AAB (i.e., two identical calls [AA] followed by a different one [B]) or ABB. Following habituation to AAB strings, rhesus monkeys showed significantly more orienting responses to novel ABB strings than to novel AAB strings. Further, following habituation to an ABB pattern, rhesus responded more in test trials to AAB than ABB. These results, combined with other parallel studies, suggest that animals can extract an identity relationship from an artificial sequence of sounds, and can do so even though the tokens are species-specific vocalizations that are never produced in this sequence. PMID:19450023

  3. Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

    PubMed

    Zhang, Zhi-Yi; Mao, Yu; Feng, Xiao-Li; Zheng, Na; Lü, Long-Bao; Ma, Yuan-Ye; Qin, Dong-Dong; Hu, Xin-Tian

    2016-06-01

    Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention.

  4. Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

    PubMed

    Zhang, Zhi-Yi; Mao, Yu; Feng, Xiao-Li; Zheng, Na; Lü, Long-Bao; Ma, Yuan-Ye; Qin, Dong-Dong; Hu, Xin-Tian

    2016-06-01

    Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention. PMID:27025444

  5. Genetic modulation of cognitive flexibility and socioemotional behavior in rhesus monkeys.

    PubMed

    Izquierdo, Alicia; Newman, Timothy K; Higley, J Dee; Murray, Elisabeth A

    2007-08-28

    In human and nonhuman primates, structural variants of the gene encoding the serotonin transporter [5-hydroxytryptamine transporter (5-HTT)] affect the transcription and functional efficacy of 5-HTT. Prior work has shown that structural variants differentially affect function of the amygdala and ventromedial prefrontal cortex (VMPFC), regions important for the regulation and expression of emotion. However, relatively little is known about the impact of 5-HTT allelic variants on cognition. To address this question, we tested rhesus monkeys carrying orthologous structural variants of 5-HTT on a battery of tasks that assess cognitive flexibility, reward processing, and emotion. Here we show that rhesus monkeys carrying two copies of the short allele (SS) of the rhesus 5-HTT gene-linked polymorphic region (rh5-HTTLPR) show significantly reduced cognitive flexibility as measured by two tasks in the battery: object discrimination reversal learning and instrumental extinction. Monkeys with the SS genotype also displayed alterations in socioemotional behavior. Genotype variation was not related to visual perceptual abilities, valuation of food rewards, or the ability to express a wide range of defensive responses. Although emotional alterations associated with 5-HTT variation have been described as the primary phenotype, the present study reports differences in at least one type of cognitive flexibility, which has not been described previously. Because behaviors modulated by the 5-HTTLPR are a subset of those dependent on the VMPFC, analysis of structural and functional correlates of gene variation in this region may inform the nature of the genetic modulation of cognition.

  6. Parallel evolutionary events in the haptoglobin gene clusters of rhesus monkey and human

    SciTech Connect

    Erickson, L.M.; Maeda, N.

    1994-08-01

    Parallel occurrences of evolutionary events in the haptoglobin gene clusters of rhesus monkeys and humans were studied. We found six different haplotypes among 11 individuals from two rhesus monkey families. The six haplotypes include two types of haptoglobin gene clusters: one type with a single gene and the other with two genes. DNA sequence analysis indicates that the one-gene and the two-gene clusters were both formed by unequal homologous crossovers between two genes of an ancestral three-gene cluster, near exon 5, the longest exon of the gene. This exon is also the location where a separate unequal homologous crossover occured in the human lineage, forming the human two-gene haptoglobin gene cluster from an ancestral three-gene cluster. The occurrence of independent homologous unequal crossovers in rhesus monkey and in human within the same region of DNA suggests that the evolutionary history of the haptoglobin gene cluster in primates is the consequence of frequent homologous pairings facilitated by the longest and most conserved exon of the gene. 27 refs., 7 figs., 1 tab.

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

    PubMed

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

    2008-08-01

    Sex differences in toy preferences in children are marked, with boys expressing stronger and more rigid toy preferences than girls, whose preferences are more flexible. 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.

  8. 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

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

    SciTech Connect

    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 the 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.

  10. Selective hippocampal lesions yield nonspatial memory impairments in rhesus monkeys.

    PubMed

    Doré, F Y; Thornton, J A; White, N M; Murray, E A

    1998-01-01

    Monkeys with removals of medial temporal lobe (MTL) structures are widely recognized as valid models of human global anterograde amnesia, a syndrome that arises consequent to damage to a finite set of brain structures situated in the medial temporal lobe and/or medial diencephalon. However, a comparison of memory deficits in human and nonhuman primates with MTL damage has presented a long-standing puzzle. Whereas amnesic patients are impaired in learning object discrimination problems, monkeys with MTL damage are typically not. One possible explanation for this difference is that object discrimination tasks for humans and monkeys differ in that the former but not the latter requires the use of contextual information. If this analysis is correct, monkeys with MTL damage might be disadvantaged in learning to discriminate similar objects presented in different contexts. To test this possibility, we evaluated the effects of excitotoxic lesions of one of the MTL structures, the hippocampus, on the rate of learning of discrimination problems embedded within unique contexts. Monkeys with hippocampal lesions were impaired relative to controls in learning object discrimination problems of this type. These findings strongly support the idea that the difference in the effect on object memory of MTL damage in human and nonhuman primates is due to a difference in the opportunity to employ contextual cues rather than to a difference in the organization of memory.

  11. Osmotic tolerance limits and properties of rhesus monkey (Macaca mulatta) spermatozoa.

    PubMed

    Rutllant, Josep; Pommer, Angela C; Meyers, Stuart A

    2003-01-01

    Fundamental cryobiological characteristics of rhesus spermatozoa must be determined for successful cryopreservation techniques to be established. The main objectives of the present study were to determine the osmotic behavior and osmotic tolerance limits of rhesus macaque spermatozoa. Cell volume changes over anisotonic conditions were assessed using an electronic particle counter and sperm motility was evaluated with a computer-assisted sperm analysis system. Analysis of membrane integrity and mitochondrial membrane potential was performed using flow cytometry. Rhesus monkey spermatozoa behave as linear osmometers in the osmotic range tested (75-900 mOsmol kg(-1)), as shown by the Boyle van't Hoff plot (r(2) =.99). Rhesus spermatozoa have a mean cell volume of 36.8 +/- 0.5 micro m(3) at 22 degrees C, with 77.2% of the intracellular volume being osmotically inactive. Results regarding sperm tolerance to osmotic stress showed that sperm motility was more sensitive than membrane integrity to deviations from isotonicity and, in addition, that rhesus sperm motility and membrane integrity were more sensitive to hypertonic than hypotonic conditions. Mitochondrial membrane potential did not explain the lack of sperm motility observed under anisosmolal conditions in our study. Although most spermatozoa were able to recover initial volume after osmotic stress, they were not able to recover initial motility.

  12. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys.

    PubMed

    Whitney, James B; Hill, Alison L; Sanisetty, Srisowmya; Penaloza-MacMaster, Pablo; Liu, Jinyan; Shetty, Mayuri; Parenteau, Lily; Cabral, Crystal; Shields, Jennifer; Blackmore, Stephen; Smith, Jeffrey Y; Brinkman, Amanda L; Peter, Lauren E; Mathew, Sheeba I; Smith, Kaitlin M; Borducchi, Erica N; Rosenbloom, Daniel I S; Lewis, Mark G; Hattersley, Jillian; Li, Bei; Hesselgesser, Joseph; Geleziunas, Romas; Robb, Merlin L; Kim, Jerome H; Michael, Nelson L; Barouch, Dan H

    2014-08-01

    The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (HIV-1) eradication strategies. However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before systemic viraemia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIVMAC251 infection. Treatment with ART on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later time points. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, after discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound as compared with those treated on days 7, 10 and 14. The time to viral rebound correlated with total viraemia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the 'eclipse' phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies.

  13. Physiological correlates of self-injurious behavior in captive, socially-reared rhesus monkeys.

    PubMed

    Tiefenbacher, S; Novak, M A; Jorgensen, M J; Meyer, J S

    2000-11-01

    This study examined the relationship between self-injurious behavior (SIB) in rhesus monkeys and several biological variables, including monoamine metabolites in cerebrospinal fluid (CSF) and circulating levels of ACTH, cortisol, and testosterone. Cisternal CSF and blood plasma samples were obtained from 23 individually housed male rhesus macaques, 14 of which had a veterinary record of self-inflicted wounding. CSF samples were analyzed for 5-hydroxyindole-3-acetic acid (5-HIAA), homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG) using isocratic high-performance liquid chromatography with electrochemical detection (HPLC-EC). Plasma samples were analyzed for ACTH, cortisol, and testosterone using commercially available radioimmunoassays (RIAs). Rates of self-directed biting were determined by systematic observation of all monkeys. Monkeys with SIB did not differ from controls in their basal monoamine or gonadal activity. However, the SIB group showed consistently lower mean plasma cortisol levels than the control group. Plasma cortisol was negatively correlated with rates of self-directed biting. These results suggest a persistent dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis in monkeys with SIB. It is not yet clear whether this phenomenon of low cortisol represents chronically reduced adrenocortical secretion under basal conditions or a difference in response to the mild stress of capture and chemical restraint. The implications of these findings will be discussed with respect to SIB in humans as well as post-traumatic stress disorder (PTSD), a condition characterized by pituitary-adrenocortical hypoactivity.

  14. A primate model for human cerebral malaria: Plasmodium coatneyi-infected rhesus monkeys.

    PubMed

    Aikawa, M; Brown, A; Smith, C D; Tegoshi, T; Howard, R J; Hasler, T H; Ito, Y; Perry, G; Collins, W E; Webster, K

    1992-04-01

    A major factor in the pathogenesis of human cerebral malaria is blockage of cerebral microvessels by the sequestration of parasitized human red blood cells (PRBC). In vitro studies indicate that sequestration of PRBC in the microvessels is mediated by the attachment of knobs on PRBC to receptors on the endothelial cell surface such as CD36, thrombospondin (TSP), and intercellular adhesion molecule-1 (ICAM-1). However, it is difficult to test this theory in vivo because fresh human brain tissues from cerebral malarial autopsy cases are not easy to obtain. Although several animal models for human cerebral malaria have been proposed, none have shown pathologic findings that are similar to those seen in humans. In order to develop an animal model for human cerebral malaria, we studied brains of rhesus monkeys infected with the primate malaria parasite, Plasmodium coatneyi. Our study demonstrated PRBC sequestration and cytoadherence of knobs on PRBC to endothelial cells in the cerebral microvessels of these monkeys. Cerebral microvessels with sequestered PRBC were shown by immunohistochemical analysis to possess CD36, TSP, and ICAM-1. These proteins were not evident in the cerebral microvessels of uninfected control monkeys. Thus, our study indicates, for the first time, that rhesus monkeys infected with P. coatneyi can be used as a primate model to study human cerebral malaria. By using this animal model, we may be able to evaluate strategies for the development of vaccines to prevent human cerebral malaria. PMID:1374220

  15. Effects of ifenprodil on the discriminative stimulus effects of cocaine in rhesus monkeys.

    PubMed

    Fujiwara, Atsushi; Wakasa, Yoshio; Hironaka, Naoyuki; Sasaki, Mikio; Iino, Masahiko; Yanagita, Tomoji

    2007-02-01

    Ifenprodil is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist which prefers NR2B-containing NMDA receptors to NR2A-containing NMDA receptors. It has been reported that ifenprodil suppresses morphine-induced place preference in mice. In this study, the effects of ifenprodil on the discriminative stimulus effects of cocaine were examined in rhesus monkeys. Five monkeys were trained to discriminate cocaine at 0.25 or 0.5 mg/kg im from saline using a standard two-lever drug-discrimination paradigm under a fixed-ratio schedule of food reinforcement. A single dose of cocaine (0.06-0.5 mg/kg) produced a dose-dependent increase in cocaine-appropriate response, and training doses produced 100% cocaine-lever response in each monkey. Pretreatment with ifenprodil (1 or 2 mg/kg, i.v.) blocked the cocaine-appropriate response when low doses of cocaine were used. The results suggest that NR2B-containing NMDA receptor-mediated mechanisms modulate the discriminative stimulus effects of cocaine in rhesus monkeys. PMID:17393777

  16. Morphological changes of an inflammatory myopathy in rhesus monkeys with simian acquired immunodeficiency syndrome.

    PubMed

    Dalakas, M C; Gravell, M; London, W T; Cunningham, G; Sever, J L

    1987-09-01

    Eleven of 25 rhesus monkeys which died of simian acquired immunodeficiency syndrome (SAIDS) caused by infection with a type D retrovirus related to Mason-Pfizer monkey virus showed evidence of muscle weakness and atrophy and had elevated levels of muscle enzymes. Biopsies of affected muscle studied with enzyme histochemistry showed the characteristic features of polymyositis. Inflammatory cells consisting of lymphocytes, macrophages, and large vacuolated bizarre-shaped cells of undetermined type were surrounding or invading muscle fibers and were present in the perivascular spaces and endomysia septa. Within the perivascular infiltrates, lymphocytes were abundant but very few macrophages were present. Other myopathic features including profound proliferation of fibrous tissue, necrosis, and phagocytosis of muscle fibers were noted to a variable degree. The retrovirus was isolated from affected muscles. The clinical and historical features of polymyositis in rhesus monkeys with SAIDS are very similar to those of human polymyositis. The polymyositis in SAIDS induced by a type D retrovirus related to Mason-Pfizer monkey virus is an excellent primate model to study the mechanism and morphological changes of viral-induced muscle damage.

  17. Impact of caloric restriction on health and survival in rhesus monkeys: the NIA study

    PubMed Central

    Mattison, Julie A.; Roth, George S.; Beasley, T. Mark; Tilmont, Edward M.; Handy, April H.; Herbert, Richard L.; Longo, Dan L.; Allison, David B.; Young, Jennifer E.; Bryant, Mark; Barnard, Dennis; Ward, Walter F.; Qi, Wenbo; Ingram, Donald K.; de Cabo, Rafael

    2013-01-01

    Life extension by calorie restriction (CR) has been widely reported in a variety of species and remains on the forefront of anti-aging intervention studies. We report healthspan and survival effects of CR from a 23-year study in rhesus macaques conducted at the National Institute on Aging (NIA). CR initiated at older ages did not increase survival relative to Controls; however, CR monkeys demonstrated an improved metabolic profile and may have less oxidative stress as indicated by plasma isoprostane levels. When initiated in young monkeys, there was a trend (p=0.06) for a delay in age-associated disease onset in CR monkeys; but again, survival curves were not improved, in contrast to another study reported in the literature. This suggests that the effects of CR in a long-lived animal are complex and likely dependent on a variety of environmental, nutritional, and genetic factors. PMID:22932268

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

    SciTech Connect

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

    1994-06-01

    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 of 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. 48 refs., 2 figs., 4 tabs.

  19. Severe dopaminergic neuron loss in rhesus monkey brain impairs morphine-induced conditioned place preference

    PubMed Central

    Yan, Ting; Rizak, Joshua Dominic; Wang, Jianhong; Yang, Shangchuan; Ma, Yuanye; Hu, Xintian

    2015-01-01

    It is well known that dopamine (DA) is critical for reward, but the precise role of DA in reward remains uncertain. The aim of this study was to determine what percentage of dopaminergic neurons in the primate brain is required for the expression of conditioned reward by measuring the performance of DA-deficient rhesus monkeys in a morphine-induced conditioned place preference (CPP) paradigm. Animals with mild Parkinsonian symptoms successfully developed and retained a morphine preference that was equivalent to control monkeys. However, these monkeys could not maintain the preference as well as controls when they retained severe Parkinsonian symptoms. On the other hand, monkeys initially in a severe Parkinsonian state developed a preference for morphine, but this preference was weaker than that of the controls. Histological results showed that the loss of dopaminergic neurons in monkeys that had severe Parkinsonian symptoms was about 80% in comparison to the control monkeys. All these data suggest that a severely impaired DA system alters rewarding-seeking behavior in non-human primates. PMID:26528155

  20. 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

  1. 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

  2. Rhesus monkey gastric mucins: oligomeric structure, glycoforms and Helicobacter pylori binding.

    PubMed Central

    Lindén, Sara; Borén, Thomas; Dubois, André; Carlstedt, Ingemar

    2004-01-01

    Mucins isolated from the stomach of Rhesus monkey are oligomeric glycoproteins with a similar mass, density, glycoform profile and tissue localization as human MUC5AC and MUC6. Antibodies raised against the human mucins recognize those from monkey, which thus appear to be orthologous to those from human beings. Rhesus monkey muc5ac and muc6 are produced by the gastric-surface epithelium and glands respectively, and occur as three distinct glycoforms. The mucins are substituted with the histo blood-group antigens B, Le(a) (Lewis a), Le(b), Le(x), Le(y), H-type-2, the Tn-antigen, the T-antigen, the sialyl-Le(x) and sialyl-Le(a) structures, and the expression of these determinants varies between individuals. At neutral pH, Helicobacter pylori strains expressing BabA (blood-group antigen-binding adhesin) bind Rhesus monkey gastric mucins via the Le(b) or H-type-1 structures, apparently on muc5ac, as well as on a smaller putative mucin, and binding is inhibited by Le(b) or H-type-1 conjugates. A SabA (sialic acid-binding adhesin)-positive H. pylori mutant binds to sialyl-Le(x)-positive mucins to a smaller extent compared with the BabA-positive strains. At acidic pH, the microbe binds to mucins substituted by sialylated structures such as sialyl-Le(x) and sialylated type-2 core, and this binding is inhibited by DNA and dextran sulphate. Thus mucin- H. pylori binding occurs via at least three different mechanisms: (1) BabA-dependent binding to Le(b) and related structures, (2) SabA-dependent binding to sialyl-Le(x) and (3) binding through a charge-mediated mechanism to sialylated structures at low pH values. PMID:14736333

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

    PubMed

    VandeVoort, Catherine A; Mtango, Namdori R; Midic, Uros; Latham, Keith E

    2015-04-01

    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.

  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. 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

  7. Quantitative analysis of male fetal DNA in maternal serum of gravid rhesus monkeys (Macaca mulatta).

    PubMed

    Jimenez, Daniel F; Tarantal, Alice F

    2003-01-01

    The isolation of human fetal DNA from the maternal circulation has provided a source of fetal material for prenatal diagnosis. The objective of this study was to investigate whether a similar pattern could be observed in the maternal circulation of male-bearing gravid rhesus monkeys. A real-time PCR TaqMan system for the rhesus Y-chromosome sex determining region was used to determine fetal sex and to quantify fetal DNA concentrations. Results in 14 healthy pregnancies indicated that fetal male DNA could be routinely detected in maternal serum by 50 d of gestation (late first trimester; term 165 +/- 10 d). Fetal DNA concentrations increased with advancing gestation, reaching a mean of 341 genome equivalents/mL of serum (range 11-1570 copies/mL) in the last trimester of gestation, similar to findings in humans. The fetal DNA concentration corresponded to 2.7% of the total maternal serum DNA in the third trimester. Similar to findings in humans, male fetal DNA sequences were not detected postpartum (through 4 wk postpartum) or in animals with a previous history of delivering male offspring. These data indicate that fetal male DNA is present in the maternal circulation of gravid rhesus monkeys comparable to findings in humans and further support the use of this nonhuman primate species as a model to investigate fetomaternal cell trafficking and microchimerism. PMID:12508077

  8. 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.

  9. Long-term effects of castration on the skeleton of male rhesus monkeys (Macaca mulatta).

    PubMed

    Kessler, Matthew J; Wang, Qian; Cerroni, Antonietta M; Grynpas, Marc D; Gonzalez Velez, Olga D; Rawlins, Richard G; Ethun, Kelly F; Wimsatt, Jeffrey H; Kensler, Terry B; Pritzker, Kenneth P H

    2016-01-01

    While osteopenia (OPE) and osteoporosis (OPO) have been studied in various species of aging nonhuman primates and extensively in ovariectomized rhesus and cynomolgus macaques, there is virtually no information on the effects of castration on the skeleton of male nonhuman primates. Most information on castrated male primates comes from a few studies on the skeletons of eunuchs. This report used a subset of the Caribbean Primate Research Center's (CPRC) Cayo Santiago (CS) rhesus macaque skeletal collection to qualitatively and quantitatively compare the bone mineral density (BMD) of castrated and age-matched intact males and, thereby, determine the long-term effects of castration (orchidectomy) on bone. Lumbar vertebrae, femora, and crania were evaluated using dual-energy X-ray absorptiometry (DEXA or DXA) and digital radiography augmented, when fresh tissues were available, with autoradiography and histology. Results confirmed physical examinations of long bones that castration causes changes in the skeleton of male rhesus macaques similar to those found in eunuchs, including OPE and OPO of the vertebrae and femora, thinning of the skull, and vertebral fractures and kyphosis of the spine more severe than that caused by normal aging alone. Also like eunuchs, some castrated CS male rhesus monkeys had a longer life span than intact males or females. Based on these results and the effects of castration on other tissues and organs of eunuchs, on behavior, hormone profiles and possibly on cognition and visual perception of human and nonhuman primates, and other mammals, castrated male rhesus macaques should be used with caution for laboratory studies and should be considered a separate category from intact males. Despite these caveats, the castrated male rhesus macaque should make an excellent animal model in which to test hormone replacement therapies for boys and men orchidectomized for testicular and prostate cancer.

  10. 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.

  11. 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

  12. Effects of estradiol on cocaine self-administration and cocaine discrimination by female rhesus monkeys.

    PubMed

    Mello, Nancy K; Negus, S Stevens; Knudson, Inge M; Kelly, Maureen; Mendelson, Jack H

    2008-03-01

    The ovarian steroid hormone, estradiol, enhances the reinforcing and locomotor activating effects of cocaine in rodents under some conditions. The present study evaluated the acute effects of estradiol benzoate (E(2)beta) on cocaine self-administration and cocaine discrimination in female rhesus monkeys. Cocaine self-administration (0.10 mg/kg/inj., i.v.) was maintained on a fixed-ratio (FR) 30 schedule of reinforcement, and monkeys had access to cocaine during one 2-h session each day. E(2)beta in a cyclodextrin vehicle (0.00001-0.01 mg/kg, i.m.) was administered 30 min before test sessions conducted twice each week. Cocaine doses were administered in an irregular order during each dose-effect curve determination (0.001-0.3 mg/kg/inj.). Blood samples were collected after test sessions to determine 17beta-estradiol levels. Banana-flavored food pellets were available on an FR 30 schedule in three 1-h sessions each day. Five monkeys were trained to discriminate cocaine (0.18 mg/kg, i.m.) from saline in a two-key food-reinforced procedure, and the effects of pretreatment with E(2)beta in cyclodextrin and in sesame oil were studied. Acute administration of E(2)beta did not consistently alter the cocaine self-administration or drug discrimination dose-effect curves in comparison to saline control treatment. Females also did not self-administer E(2)beta (0.00001-0.10 mg/kg, i.v.) above saline levels. Finally, E(2)beta (0.0001-0.01 mg/kg, i.m.) did not substitute for cocaine in monkeys trained to discriminate cocaine from saline. Taken together, these data suggest that over the dose range studied, estradiol administration does not consistently alter the abuse-related effects of cocaine in female rhesus monkeys. PMID:17507915

  13. Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys.

    PubMed Central

    Yasutomi, Y; Reimann, K A; Lord, C I; Miller, M D; Letvin, N L

    1993-01-01

    To assess the possible role of cytotoxic T lymphocytes (CTLs) in containing the spread of human immunodeficiency virus in acutely infected individuals, the temporal evolution of the virus-specific CD8+ lymphocyte response was defined in simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys. A brief period of SIVmac plasma antigenemia was seen 9 to 16 days following intravenous infection with SIVmac, ending as the absolute number of CD8+ peripheral blood lymphocytes (PBLs) increased. In a prospective assessment of the ability of CD8+ lymphocytes of these monkeys to suppress SIVmac replication in autologous PBLs, inhibitory activity was detected as early as 4 days, with a more pronounced effect 12 to 16 days following infection. SIVmac Gag- and Nef-specific CD8+ effector cell activities were demonstrable in PBLs of animals by 2 weeks following virus inoculation. In fact, SIVmac-specific CTL precursors were documented in the PBLs of rhesus monkeys 4 to 6 days after SIVmac infection. These studies indicate that AIDS virus-specific CD8+ CTLs are present in PBLs within days of infection and may play an important role in containing the early spread of virus. PMID:8437240

  14. Aging increases mitochondrial DNA damage and oxidative stress in liver of rhesus monkeys

    PubMed Central

    Castro, María del R.; Suarez, Edu; Kraiselburd, Edmundo; Isidro, Angel; Paz, José; Ferder, León; Ayala-Torres, Sylvette

    2013-01-01

    While the mechanisms of cellular aging remain controversial, a leading hypothesis is that mitochondrial oxidative stress and mitochondrial dysfunction play a critical role in this process. Here, we provide data in aging rhesus macaques supporting the hypothesis that increased oxidative stress is a major characteristic of aging and may be responsible for the age-associated increase in mitochondrial dysfunction. We measured mitochondrial DNA (mtDNA) damage by quantitative PCR in liver and peripheral blood mononuclear cells of young, middle age, and old monkeys and show that older monkeys have increases in the number of mtDNA lesions. There was a direct correlation between the amount of mtDNA lesions and age, supporting the role of mtDNA damage in the process of aging. Liver from older monkeys showed significant increases in lipid peroxidation, protein carbonylations and reduced antioxidant enzyme activity. Similarly, peripheral blood mononuclear cells from the middle age group showed increased levels in carbonylated proteins, indicative of high levels of oxidative stress. Together, these results suggest that the aging process is associated with defective mitochondria, where increased production of reactive oxygen species results in extensive damage at the mtDNA and protein levels. This study provides valuable data based on the rhesus macaque model further validating age-related mitochondrial functional decline with increasing age and suggesting that mtDNA damage might be a good biomarker of aging. PMID:22027539

  15. Development of a Cognitive Testing Apparatus for Socially Housed Mother-Peer-Reared Infant Rhesus Monkeys

    PubMed Central

    Dettmer, Amanda M.; Murphy, Ashley M.; Suomi, Stephen J.

    2014-01-01

    Though cognitive testing of infant monkeys has been practiced for the past 40 years, these assessments have been limited primarily to nursery-reared infants due to the confounds of separating mother-reared infants for assessments. Here we describe a pilot study in which we developed a cognitive testing apparatus for socially housed, mother-peer-reared rhesus macaques under one year of age (Macaca mulatta) that allowed the infants to freely return to their mothers for contact comfort. Infants aged 151.2±18.3 days (mean±SEM; n=5) were trained and tested on an object detour reach task. Infants completed training in 5.0±0.2 days, and completed testing in 6.2±0.9 days. Across four days of testing, infants improved to nearly errorless performance (Friedman test: χ2=13.27, df=3, p=0.004) and learned to do the task more quickly (Friedman test: χ2=11.69, df=3, p=0.009). These are the first cognitive data in group-housed, mother-peer-reared rhesus monkeys under one year of age, and they underscore the utility of this apparatus for studying cognitive development in a normative population of infant monkeys. PMID:25782609

  16. Serotonin transporter gene polymorphism, differential early rearing, and behavior in rhesus monkey neonates.

    PubMed

    Champoux, M; Bennett, A; Shannon, C; Higley, J D; Lesch, K P; Suomi, S J

    2002-01-01

    A polymorphism in the serotonin (5-HT) transporter gene regulatory region (5-HTTLPR) is associated with measures of 5-HT transporter (5-HTT) expression and 5-HT-mediated behaviors in humans. An analogous length variation of the 5-HTTLPR has been reported in rhesus monkeys (rh5-HTTLPR). A retrospective association study was conducted on 115 rhesus macaque infants either homozygous for the long 5HTTLPR variant (l/l) or heterozygous for the short and long form (l/s). To assess contributions of genotype and early rearing environment, 36 mother-reared monkeys (l/l = 26, l/s = 10) and 79 nursery-reared monkeys (l/l = 54, l/s = 25) were assessed on days 7, 14, 21, and 30 of life on a standardized primate neurobehavioral test designed to measure orienting, motor maturity, reflex functioning, and temperament. Both mother-reared and nursery-reared heterozygote animals demonstrated increased affective responding relative to l/l homozygotes. Nursery-reared, but not mother-reared, l/s infants exhibited lower orientation scores than their l/l counterparts. These results demonstrate the contributions of rearing environment and genetic background, and their interaction, in a nonhuman primate model of behavioral development.

  17. Autoradiographic localization of aromatic hydrocarbon receptor (AHR) in rhesus monkey ovary.

    PubMed

    Baldridge, Monika G; Hutz, Reinhold J

    2007-06-01

    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most toxic congener of a large class of manmade pollutants that persist in the environment. TCDD exerts its toxic effects, in part, by binding to its receptor known as the aromatic hydrocarbon receptor (AHR). TCDD is estrogen modulatory and in some systems its receptor associates directly with estrogen receptors via co-activator molecules. TCDD inhibits steroid synthesis in human ovarian granulosa cells and AHR is found in these cells. We have previously shown that AHR is found in whole rhesus monkey ovary, but have yet to establish its location. In the present study, we set out to show that radiolabeled TCDD binds to monkey ovarian follicles and that this binding is receptor mediated. Ovaries from Macaca mulatta were sectioned on a cryostat at 10 micro m; and sections were incubated with either control vehicle, (3)H-TCDD, or (3)H-TCDD plus alpha-naphthoflavone (ANF), a known receptor-blocking agent. Here, we show for the first time specific binding of TCDD to the granulosa cells of antral follicles and other regions of the rhesus monkey ovary. Our data indicate a 60-fold increase in binding with (3)H-TCDD over that of control, and that this binding is reduced to the levels seen in controls with the addition of the competitive antagonist ANF. These findings support the hypothesis that TCDD directly affects primate ovarian function via the AHR.

  18. Reinforcing and discriminative stimulus effects of 1-benzylpiperazine and trifluoromethylphenylpiperazine in rhesus monkeys.

    PubMed

    Fantegrossi, W E; Winger, G; Woods, J H; Woolverton, W L; Coop, A

    2005-02-14

    1-Benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP) are two designer drugs that are often sold in combination tablets via the internet. The discriminative stimulus properties and reinforcing effects of these compounds have not previously been assessed in laboratory primates. In this regard, the reinforcing effects of BZP and TFMPP (alone, and in combination) were assessed via intravenous self-administration in rhesus monkeys previously trained to self-administer cocaine, while the discriminative stimulus effects of these compounds were determined in rhesus monkeys trained to discriminate amphetamine (AMPH) from saline. BZP was an effective reinforcer in self-administration tests, and appeared to induce long-lasting direct effects on behavior following sessions where BZP intakes were large. Additionally, BZP occasioned AMPH-appropriate responding in a dose-dependent manner, and produced full generalization in all monkeys tested. In contrast, TFMPP was not self-administered by any subjects and occasioned essentially no AMPH-appropriate responding at any dose tested. Non-contingent TFMPP administration had direct effects on behavior and abolished subsequent cocaine-maintained responding. Similarly, self-administration of various ratios of BZP:TFMPP combinations engendered less responding than did BZP alone. The present results suggest that BZP has abuse liability of the amphetamine type, but that such effects are not shared by TFMPP. PMID:15664717

  19. 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.

  20. Sonar biparietal diameter growth standards in the rhesus monkey.

    PubMed

    Sabbagha, R E; Turner, J H; Chez, R A

    1975-02-01

    Serial sonar fetal cephalometry was performed on 67 pregnant monkeys (Macaca ulatta) with known breeding dates. A normal biparietal diameter (BPD) growth curve was constructed along four percentile divisions; namely, the 10th to the 24th, 25th to the 49th, 50th to the 74th, and the 75th to the 90th. It is shown that under normal conditions fetuses initially positioned in any one of these divisions will continue to grow within the confines of that same percentile range. This biologic phenomenon has not been previously reported. It is significant because it leads to a more precise separation of normal vs. suboptimal intrauterine growth.

  1. 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

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

    PubMed Central

    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

    2016-01-01

    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. PMID:27534985

  3. Laterality affects spontaneous recovery of contralateral hand motor function following motor cortex injury in rhesus monkeys.

    PubMed

    Darling, Warren G; Helle, Nicole; Pizzimenti, Marc A; Rotella, Diane L; Hynes, Stephanie M; Ge, Jizhi; Stilwell-Morecraft, Kimberly S; Morecraft, Robert J

    2013-07-01

    The purpose of this study was to test whether brain laterality influences spontaneous recovery of hand motor function after controlled brain injuries to arm areas of M1 and lateral premotor cortex (LPMC) of the hemisphere contralateral to the preferred hand in rhesus monkeys. We hypothesized that monkeys with stronger hand preference would exhibit poorer recovery of skilled hand use after such brain injury. Degree of handedness was assessed using a standard dexterity board task in which subjects could use either hand to retrieve small food pellets. Fine hand/digit motor function was assessed using a modified dexterity board before and after the M1 and LPMC lesions in ten monkeys. We found a strong negative relationship between the degree of handedness and the recovery of manipulation skill, demonstrating that higher hand preference was associated with poorer recovery of hand fine motor function. We also observed that monkeys with larger lesions within M1 and LPMC had greater initial impairment of manipulation and poorer recovery of reaching skill. We conclude that monkeys with a stronger hand preference are likely to show poorer recovery of contralesional hand fine motor skill after isolated brain lesions affecting the lateral frontal motor areas. These data may be extended to suggest that humans who exhibit weak hand dominance, and perhaps individuals who use both hands for fine motor tasks, may have a more favorable potential for recovery after a unilateral stroke or brain injury affecting the lateral cortical motor areas than individuals with a high degree of hand dominance.

  4. Rhesus monkeys show human-like changes in gaze following across the lifespan.

    PubMed

    Rosati, Alexandra G; Arre, Alyssa M; Platt, Michael L; Santos, Laurie R

    2016-05-11

    Gaze following, or co-orienting with others, is a foundational skill for human social behaviour. The emergence of this capacity scaffolds critical human-specific abilities such as theory of mind and language. Non-human primates also follow others' gaze, but less is known about how the cognitive mechanisms supporting this behaviour develop over the lifespan. Here we experimentally tested gaze following in 481 semi-free-ranging rhesus macaques (Macaca mulatta) ranging from infancy to old age. We found that monkeys began to follow gaze in infancy and this response peaked in the juvenile period-suggesting that younger monkeys were especially attuned to gaze information, like humans. After sexual maturity, monkeys exhibited human-like sex differences in gaze following, with adult females showing more gaze following than males. Finally, older monkeys showed reduced propensity to follow gaze, just as older humans do. In a second study (n = 80), we confirmed that macaques exhibit similar baseline rates of looking upwards in a control condition, regardless of age. Our findings indicate that-despite important differences in human and non-human primate life-history characteristics and typical social experiences-monkeys undergo robust ontogenetic shifts in gaze following across early development, adulthood and ageing that are strikingly similar to those of humans.

  5. Rhesus monkeys show human-like changes in gaze following across the lifespan.

    PubMed

    Rosati, Alexandra G; Arre, Alyssa M; Platt, Michael L; Santos, Laurie R

    2016-05-11

    Gaze following, or co-orienting with others, is a foundational skill for human social behaviour. The emergence of this capacity scaffolds critical human-specific abilities such as theory of mind and language. Non-human primates also follow others' gaze, but less is known about how the cognitive mechanisms supporting this behaviour develop over the lifespan. Here we experimentally tested gaze following in 481 semi-free-ranging rhesus macaques (Macaca mulatta) ranging from infancy to old age. We found that monkeys began to follow gaze in infancy and this response peaked in the juvenile period-suggesting that younger monkeys were especially attuned to gaze information, like humans. After sexual maturity, monkeys exhibited human-like sex differences in gaze following, with adult females showing more gaze following than males. Finally, older monkeys showed reduced propensity to follow gaze, just as older humans do. In a second study (n = 80), we confirmed that macaques exhibit similar baseline rates of looking upwards in a control condition, regardless of age. Our findings indicate that-despite important differences in human and non-human primate life-history characteristics and typical social experiences-monkeys undergo robust ontogenetic shifts in gaze following across early development, adulthood and ageing that are strikingly similar to those of humans. PMID:27170712

  6. Metabolism of kadsurenone and 9,10-dihydrokadsurenone in rhesus monkeys and rat liver microsomes

    SciTech Connect

    Thompson, K.L.; Chang, M.N.; Chabala, J.C.; Chiu, S.H.; Eline, D.; Hucker, H.B.; Sweeney, B.M.; White, S.D.; Arison, B.H.; Smith, J.L.

    1988-09-01

    The metabolism of the PAF antagonists kadsurenone and tritium-labeled 9,10-dihydrokadsurenone was studied in rhesus monkeys and rat liver microsomes. The monkey metabolites of the two drugs were isolated as their glucuronide conjugates from the urine of iv dosed males. The metabolites from both monkey and microsomal metabolism were purified by reverse phase HPLC and identified by spectral (NMR, UV, and mass spectrometric) analysis. The principal pathway of biotransformation of the tritium-labeled 9,10-dihydrokadsurenone in monkeys was hydroxylation of the C-5 propyl side chain to give two metabolites, 10-hydroxy-9,10-dihydrokadsurenone and 9-hydroxy-9,10-dihydrokadsurenone. These compounds were excreted as glucuronides. Microsomal incubation of tritium-labeled 9,10-dihydrokadsurenone yielded the 10-, 9-, and 8-hydroxy-9,10-dihydrokadsurenone as major metabolites. Kadsurenone was also metabolized at the C-5 side chain, an allyl group. The monoglucuronide of 9,10-dihydroxykadsurenone was isolated from monkey urine. Spectral analysis was not definitive as to the site of conjugation, and the structure of the metabolite was assigned as the C-10 conjugate. A major metabolite of rat liver microsomal incubation of kadsurenone was 9,10-dihydroxykadsurenone.

  7. Effects of chronic methylphenidate in adolescence on later methylphenidate self-administration in rhesus monkeys.

    PubMed

    Martelle, Susan E; Porrino, Linda J; Nader, Michael A

    2013-09-01

    Many children diagnosed with attention deficit hyperactivity disorder are treated with methylphenidate (MPH), despite limited information on later vulnerability to drug abuse. A previous study in adolescent monkeys treated with MPH for 1 year did not indicate differences in acquisition to cocaine reinforcement compared with controls. The present study extended this characterization to include MPH self-administration. Adolescent male rhesus monkeys treated previously with a sustained-release formulation of MPH (beginning at ∼30 months old) and control monkeys (n=8/group) were used. All had previous experience of self-administering cocaine under a fixed-ratio 30 schedule of reinforcement. Responding was maintained by food (1.0-g banana-flavored pellets) and MPH (saline, 0.001-0.1 mg/kg/injection) was substituted for food for at least five consecutive sessions. MPH functioned as a reinforcer in all monkeys; there were no differences between groups in MPH self-administration. These findings extend earlier research with cocaine reinforcement showing that MPH treatment in adolescent monkeys does not increase future reinforcing effects of stimulant drugs. PMID:23903242

  8. Delay discounting in rhesus monkeys: equivalent discounting of more and less preferred sucrose concentrations.

    PubMed

    Freeman, Kevin B; Nonnemacher, J Emily; Green, Leonard; Myerson, Joel; Woolverton, William L

    2012-03-01

    Humans discount larger amounts of a delayed reinforcer less steeply than smaller amounts, but studies with pigeons and rats have yet to reveal such a magnitude effect, suggesting that the effect may be unique to humans. The present study examined whether the magnitude effect is observed in a species phylogenetically closer to humans, by comparing the rates at which rhesus monkeys discounted 10% and 20% concentrations of sucrose. There were no systematic differences in the rates at which the monkeys discounted the two sucrose concentrations, despite the fact that they strongly preferred the 20% concentration. Interestingly, the monkeys discounted delayed sucrose at a rate higher than was observed with delayed cocaine, and lower than was observed with delayed saccharin in previous studies (Freeman et al. Behavioural Processes, 82, 214-218, 2009; Woolverton et al. Experimental and Clinical Psychopharmacology, 15, 238-244, 2007). Taken together, these findings suggest that although both quantitative and qualitative differences can affect monkeys' preferences between immediate reinforcers, qualitative differences between types of reinforcers (e.g., sucrose vs. cocaine) can affect monkeys' discounting rates in a way that quantitative differences within a reinforcer (e.g., 10% vs. 20% sucrose) do not. PMID:21870212

  9. Spontaneous voice–face identity matching by rhesus monkeys for familiar conspecifics and humans

    PubMed Central

    Sliwa, Julia; Duhamel, Jean-René; Pascalis, Olivier; Wirth, Sylvia

    2011-01-01

    Recognition of a particular individual occurs when we reactivate links between current perceptual inputs and the previously formed representation of that person. This recognition can be achieved by identifying, separately or simultaneously, distinct elements such as the face, silhouette, or voice as belonging to one individual. In humans, those different cues are linked into one complex conceptual representation of individual identity. Here we tested whether rhesus macaques (Macaca mulatta) also have a cognitive representation of identity by evaluating whether they exhibit cross-modal individual recognition. Further, we assessed individual recognition of familiar conspecifics and familiar humans. In a free preferential looking time paradigm, we found that, for both species, monkeys spontaneously matched the faces of known individuals to their voices. This finding demonstrates that rhesus macaques possess a cross-modal cognitive representation of individuals that extends from conspecifics to humans, revealing the adaptive potential of identity recognition for individuals of socioecological relevance. PMID:21220340

  10. Inhalation anesthetic-induced neuronal damage in the developing rhesus monkey.

    PubMed

    Zou, Xiaoju; Liu, Fang; Zhang, Xuan; Patterson, Tucker A; Callicott, Ralph; Liu, Shuliang; Hanig, Joseph P; Paule, Merle G; Slikker, William; Wang, Cheng

    2011-01-01

    The combination of nitrous oxide gas (N(2)O) and isoflurane (ISO) vapor is commonly used in pediatric surgical procedures for human infants and children to produce unconsciousness and analgesia. Because of obvious limitations it is difficult to thoroughly explore the effects of pediatric anesthetic agents on neurons in human infants or children. Due to the complexity of the primate brain, the monkey is often the animal model of choice for developmental neurotoxicology experiments, and it is in the rhesus monkey that the phenomenon of interest (anesthetic-induced neuronal cell death in the brain) has been previously reported. Recent reports indicate that exposure of the developing brain to general anesthetics that block N-methyl-D-aspartate (NMDA)-type glutamate receptors or potentiate gamma-aminobutyric acid (GABA) receptors can trigger widespread apoptotic cell death in rodents. The present study was performed to determine whether prolonged exposure of developing nonhuman primates to a clinically relevant combination of nitrous oxide and isoflurane produces neuronal damage. Postnatal day (PND) 5-6 rhesus monkeys were exposed to N(2)O (70%) or ISO (1.0%) alone, or N(2)O plus ISO for 8 h. Inhalation of the combination of 70% N(2)O+1% ISO produces a surgical plane of anesthesia. Six hours after completion of anesthetic administration the monkeys were examined for neurotoxic effects. No significant neurotoxic effects were observed for the monkeys exposed to N(2)O or ISO alone. However, neuronal damage was apparent when N(2)O was combined with ISO as indicated by increased numbers of caspase-3-, Silver staining- and Fluoro-Jade C-positive cells in the frontal cortex, temporal gyrus and hippocampus. Electron micrographs indicated typical swelling of the cytoplasm and nuclear condensation in the frontal cortex. These data suggest that prolonged exposure to inhaled anesthetics (a combination of N(2)O and ISO) in the developing rhesus monkey results in neuronal damage, and

  11. Transplantation of Adult Monkey Neural Stem Cells into A Contusion Spinal Cord Injury Model in Rhesus Macaque Monkeys

    PubMed Central

    Hajinasrollah, Mostafa; Zare Mehrjerdi, Nargess; Azizi, Hossein; Hemmesi, Katayoun; Moghiminasr, Reza; Azhdari, Zahra; Talebi, Ardeshir; Mohitmafi, Soroush; Vosough Taqi Dizaj, Ahmad; Sharifi, Giuve; Baharvand, Hossein; Rezaee, Omidvar; Kiani, Sahar

    2014-01-01

    Objective Currently, cellular transplantation for spinal cord injuries (SCI) is the subject of numerous preclinical studies. Among the many cell types in the adult brain, there is a unique subpopulation of neural stem cells (NSC) that can self-renew and differentiate into neurons. The study aims, therefore, to explore the efficacy of adult monkey NSC (mNSC) in a primate SCI model. Materials and Methods In this experimental study, isolated mNSCs were analyzed by flow cytometry, immunocytochemistry, and RT-PCR. Next, BrdU-labeled cells were transplanted into a SCI model. The SCI animal model was confirmed by magnetic resonance imaging (MRI) and histological analysis. Animals were clinically observed for 6 months. Results Analysis confirmed homing of mNSCs into the injury site. Transplanted cells expressed neuronal markers (TubIII). Hind limb performance improved in trans- planted animals based on Tarlov’s scale and our established behavioral tests for monkeys. Conclusion Our findings have indicated that mNSCs can facilitate recovery in contusion SCI models in rhesus macaque monkeys. Additional studies are necessary to determine the im- provement mechanisms after cell transplantation. PMID:24567941

  12. Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection.

    PubMed

    Pichyangkul, Sathit; Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Im-Erbsin, Rawiwan; Boonnak, Kobporn; Thitithayanont, Arunee; Jongkaewwattana, Anan; Wiboon-ut, Suwimon; Mongkolsirichaikul, Duangrat; Mahanonda, Rangsini; Spring, Michele; Chuang, Ilin; Mason, Carl J; Saunders, David L

    2015-11-01

    Studies of influenza-specific immune responses in humans have largely assessed systemic responses involving serum Ab and peripheral blood T cell responses. However, recent evidence indicates that tissue-resident memory T (TRM) cells play an important role in local murine intrapulmonary immunity. Rhesus monkeys were pulmonary exposed to 2009 pandemic H1N1 virus at days 0 and 28 and immune responses in different tissue compartments were measured. All animals were asymptomatic postinfection. Although only minimal memory immune responses were detected in peripheral blood, a high frequency of influenza nucleoprotein-specific memory T cells was detected in the lung at the "contraction phase," 49-58 d after second virus inoculation. A substantial proportion of lung nucleoprotein-specific memory CD8(+) T cells expressed CD103 and CD69, phenotypic markers of TRM cells. Lung CD103(+) and CD103(-) memory CD8(+) T cells expressed similar levels of IFN-γ and IL-2. Unlike memory T cells, spontaneous Ab secreting cells and memory B cells specific to influenza hemagglutinin were primarily observed in the mediastinal lymph nodes. Little difference in systemic and local immune responses against influenza was observed between young adult (6-8 y) and old animals (18-28 y). Using a nonhuman primate model, we revealed substantial induction of local T and B cell responses following 2009 pandemic H1N1 infection. Our study identified a subset of influenza-specific lung memory T cells characterized as TRM cells in rhesus monkeys. The rhesus monkey model may be useful to explore the role of TRM cells in local tissue protective immunity after rechallenge and vaccination. PMID:26408671

  13. Effects of Vestibular Prosthesis Electrode Implantation and Stimulation on Hearing in Rhesus Monkeys

    PubMed Central

    Dai, Chenkai; Fridman, Gene Y.; Della Santina, Charles C.

    2011-01-01

    To investigate the effects of vestibular prosthesis electrode implantation and activation on hearing in rhesus monkeys, we measured auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) in four rhesus monkeys before and after unilateral implantation of vestibular prosthesis electrodes in each of 3 left semicircular canals (SCC). Each of the 3 left SCCs were implanted with electrodes via a transmastoid approach. Right ears, which served as controls, were not surgically manipulated. Hearing tests were conducted before implantation (BI) and then 4 weeks post implantation both without electrical stimulation (NS) and with electrical stimulation (S). During the latter condition, prosthetic electrical stimuli encoding 3 dimensions of head angular velocity were delivered to the 3 ampullary branches of the left vestibular nerve via each of 3 electrode pairs of a multichannel vestibular prosthesis. Electrical stimuli comprised charge-balanced biphasic pulses at a baseline rate of 94 pulses/sec, with pulse frequency modulated from 48–222 pulses/s by head angular velocity. ABR hearing thresholds to clicks and tone pips at 1, 2, and 4 kHz increased by 5–10 dB from BI to NS and increased another ~5 dB from NS to S in implanted ears. No significant change was seen in right ears. DPOAE amplitudes decreased by 2–14 dB from BI to NS in implanted ears. There was a slight but insignificant decrease of DPOAE amplitude and a corresponding increase of DPOAE/Noise floor ratio between NS and S in implanted ears. Vestibular prosthesis electrode implantation and activation have small but measurable effects on hearing in rhesus monkeys. Coupled with the clinical observation that patients with cochlear implants only rarely exhibit signs of vestibular injury or spurious vestibular nerve stimulation, these results suggest that although implantation and activation of multichannel vestibular prosthesis electrodes in human will carry a risk of hearing loss

  14. Tissue Distribution of Memory T and B Cells in Rhesus Monkeys following Influenza A Infection

    PubMed Central

    Yongvanitchit, Kosol; Limsalakpetch, Amporn; Kum-Arb, Utaiwan; Im-Erbsin, Rawiwan; Boonnak, Kobporn; Thitithayanont, Arunee; Jongkaewwattana, Anan; Wiboon-ut, Suwimon; Mongkolsirichaikul, Duangrat; Mahanonda, Rangsini; Spring, Michele; Chuang, Ilin; Mason, Carl J.; Saunders, David L.

    2015-01-01

    Studies of influenza-specific immune responses in humans have largely assessed systemic responses involving serum Ab and peripheral blood T cell responses. However, recent evidence indicates that tissue-resident memory T (TRM) cells play an important role in local murine intrapulmonary immunity. Rhesus monkeys were pulmonary exposed to 2009 pandemic H1N1 virus at days 0 and 28 and immune responses in different tissue compartments were measured. All animals were asymptomatic postinfection. Although only minimal memory immune responses were detected in peripheral blood, a high frequency of influenza nucleoprotein–specific memory T cells was detected in the lung at the “contraction phase,” 49–58 d after second virus inoculation. A substantial proportion of lung nucleoprotein-specific memory CD8+ T cells expressed CD103 and CD69, phenotypic markers of TRM cells. Lung CD103+ and CD103- memory CD8+ T cells expressed similar levels of IFN-γ and IL-2. Unlike memory T cells, spontaneous Ab secreting cells and memory B cells specific to influenza hemagglutinin were primarily observed in the mediastinal lymph nodes. Little difference in systemic and local immune responses against influenza was observed between young adult (6–8 y) and old animals (18–28 y). Using a nonhuman primate model, we revealed substantial induction of local T and B cell responses following 2009 pandemic H1N1 infection. Our study identified a subset of influenza-specific lung memory T cells characterized as TRM cells in rhesus monkeys. The rhesus monkey model may be useful to explore the role of TRM cells in local tissue protective immunity after rechallenge and vaccination. PMID:26408671

  15. Hemorrhagic lesions in stomach of rhesus monkey caused by a piscine ascaridoid nematode.

    PubMed

    Overstreet, R M; Meyer, G W

    1981-04-01

    Within a few hours after being administered to the rhesus monkey (Macaca mulatta), Hysterothylacium type MB larvae penetrated the stomach wall, causing hemorrhage and attracting eosinophils. Inocula up to 300 larvae, however, did not cause peripheral hypereosinophilia. This species is the first ascaridoid which normally matures in fish that has been shown to penetrate the alimentary tract of a primate. Consequently, human consumption of raw seafood from at least the northern Gulf of Mexico free from infections, with Anisakis spp., Phocanema decipiens, or other species that mature in mammals or birds does not necessarily assure freedom from anisakiasis as previously assumed. PMID:6972442

  16. A novel kindling model of temporal lobe epilepsy in rhesus monkeys induced by Coriaria lactone.

    PubMed

    Hong, Zhen; Yang, Tian-Hua; Tang, Ming-Hai; Zhang, Heng; Li, Hong-Xia; Chen, Lei; Chen, Qin; Zhou, Dong

    2013-12-01

    One of the major challenges in developing novel therapeutics for human epileptic disorders derives from the limitation of knowledge of the processes by which epilepsy is generated (epileptogenesis). Furthermore, the inability to obtain human samples at the early stage of epilepsy hinders studies designed to further understand epileptogenesis. Thus, an effective animal model is critical for studies investigating this process. The purpose of this study was to establish a new primate kindling model of temporal lobe epilepsy (TLE) as an animal model of epileptogenesis. Here, repeated injections of Coriaria lactone (CL) at a subthreshold dose elicited partial seizures that culminated in secondarily generalized tonic-clonic seizures. The sequence of events and features of the behaviors observed in this model simulated those observed in human TLE. Electroencephalogram monitoring revealed the temporal lobe origins of the epileptiform potentials, which were consistent with the behavioral changes observed. A total of 7 rhesus monkeys (78%) were kindled with a median of 48 (41 to 60) CL injections. Both the seizure-induction and mortality rates were dose-dependent. A CL injection at 1.50mg/kg showed the lowest animal mortality rate (0%) and the highest seizure-induction rate (100%). Extensive kindling by CL injections with a median of 97 injections (overkindling) subsequently resulted in the recurrence of spontaneous seizures in rhesus monkeys with frequency patterns that were similar to those observed in human TLE. In addition, rhesus monkeys subjected to large numbers of kindling stimuli displayed mitochondrial damage and astrocyte activation in a pattern that was similar to the neuropathological changes characteristic of human TLE. Thus, a kindling TLE model in rhesus monkeys representing a primate animal model of epileptogenesis was established for the first time using repeated intramuscular injections of Coriaria lactone. This model was easily and efficiently performed

  17. Application of a computer serial probe recognition (SPR) task in Rhesus Monkeys (Macaca Mulatta). Final report

    SciTech Connect

    Finger, A.V.; Kahler, D.W.

    1992-11-01

    The Serial Probe Recognition (SPR) task was established to fulfill a requirement for a nonhuman primate behavioral task as a final screening of candidate compound for the pretreatment and treatment (PT) against chemical warfare agents. Initially, equipment on hand was reconfigured to support this requirement. From this prototype, we designed and developed a behavioral testing system to study SPR memory in nonhuman primates. Our system consisted of an operant chamber, a personal computer with a monitor, a touch sensitive screen, a pellet dispenser and an interface system. In this report we describe the development and application of the behavioral testing system in our laboratory. Serial probe recognition, Behavior, Training Rhesus Monkeys, Macaca Mulatta.

  18. The effect of oral contraceptives in malaria infections in rhesus monkeys*

    PubMed Central

    Collins, William E.; Campbell, Carlos C.; Barber, Ann; Skinner, Jimmie C.; Huong, Alan Y.

    1984-01-01

    Rhesus monkeys, Macaca mulatta, were treated with the oral contraceptives Brevicon (norethisterone with ethinylestradiol) and Ovral (norgestrel with ethinylestradiol), and subsequently inoculated with the simian malaria parasites Plasmodium cynomologi bastianellii or P. coatneyi. Parasitological, serological, and serum biochemical studies indicated that although there were some significant differences, in general the patterns of response to infection in both treated and control animals were similar. During the primary infection, however, Brevicon resulted in increased levels of parasitaemia, whereas Ovral resulted in decreased parasitaemias, as compared with the untreated control animals. There were no differences in the responses following secondary parasite infection. PMID:6333297

  19. A Characterization of Aerosolized Sudan Virus Infection in African Green Monkeys, Cynomolgus Macaques, and Rhesus Macaques

    PubMed Central

    Zumbrun, Elizabeth E.; Bloomfield, Holly A.; Dye, John M.; Hunter, Ty C.; Dabisch, Paul A.; Garza, Nicole L.; Bramel, Nicholas R.; Baker, Reese J.; Williams, Roger D.; Nichols, Donald K.; Nalca, Aysegul

    2012-01-01

    Filoviruses are members of the genera Ebolavirus, Marburgvirus, and “Cuevavirus”. Because they cause human disease with high lethality and could potentially be used as a bioweapon, these viruses are classified as CDC Category A Bioterrorism Agents. Filoviruses are relatively stable in aerosols, retain virulence after lyophilization, and can be present on contaminated surfaces for extended periods of time. This study explores the characteristics of aerosolized Sudan virus (SUDV) Boniface in non-human primates (NHP) belonging to three different species. Groups of cynomolgus macaques (cyno), rhesus macaques (rhesus), and African green monkeys (AGM) were challenged with target doses of 50 or 500 plaque-forming units (pfu) of aerosolized SUDV. Exposure to either viral dose resulted in increased body temperatures in all three NHP species beginning on days 4–5 post-exposure. Other clinical findings for all three NHP species included leukocytosis, thrombocytopenia, anorexia, dehydration, and lymphadenopathy. Disease in all of the NHPs was severe beginning on day 6 post-exposure, and all animals except one surviving rhesus macaque were euthanized by day 14. Serum alanine transaminase (ALT) and aspartate transaminase (AST) concentrations were elevated during the course of disease in all three species; however, AGMs had significantly higher ALT and AST concentrations than cynos and rhesus. While all three species had detectable viral load by days 3-4 post exposure, Rhesus had lower average peak viral load than cynos or AGMs. Overall, the results indicate that the disease course after exposure to aerosolized SUDV is similar for all three species of NHP. PMID:23202456

  20. 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.

  1. Effects of maternal mobility, partner, and endocrine state on social responsiveness of adolescent rhesus monkeys.

    PubMed

    Anderson, C O; Kenney, A M; Mason, W A

    1977-09-01

    The social behavior of rhesus monkeys raised for the 1st year of life with mobile (MS) or stationary (SS) cloth surrogate mothers was investigated when the animals reached 4-5 yr of age. The MS males generally refrained from social interaction during initial pairings with females, whereas SS males interacted frequently, but were more often the targets of attacks and chases from adult females than were MS males. The MS males were more likely to vary their social behavior according to the behavior of the social partner and seemed to benefit more from extended social exposure than their SS counterparts. The MS females were more similar to wild-born females than were SS females in nearly every behavior category and dimension tested. These results suggest that rearing with mobile artificial mothers improves the chances of later adaptive social adjustments in socially restricted monkeys. PMID:410688

  2. Early prenatal androgenization results in diminished ovarian reserve in adult female rhesus monkeys

    PubMed Central

    Dumesic, D.A.; Patankar, M.S.; Barnett, D.K.; Lesnick, T.G.; Hutcherson, B.A.; Abbott, D.H.

    2009-01-01

    BACKGROUND Early prenatal androgenization (PA) accelerates follicle differentiation and impairs embryogenesis in adult female rhesus monkeys (Macaca mulatta) undergoing FSH therapy for IVF. To determine whether androgen excess in utero affects follicle development over time, this study examines whether PA exposure, beginning at gestational days 40–44 (early treated) or 100–115 (late treated), alters the decline in serum anti-Mullerian hormone (AMH) levels with age in adult female rhesus monkeys and perturbs their ovarian response to recombinant human FSH (rhFSH) therapy for IVF. METHODS Thirteen normal (control), 11 early-treated and 6 late-treated PA adult female monkeys had serum AMH levels measured at random times of the menstrual cycle or anovulatory period. Using some of the same animals, basal serum AMH, gonadotrophins and steroids were also measured in six normal, five early-treated and three late-treated PA female monkeys undergoing FSH therapy for IVF during late-reproductive life (>17 years); serum AMH also was measured on day of HCG administration and at oocyte retrieval. RESULTS Serum AMH levels in early-treated PA females declined with age to levels that were significantly lower than those of normal (P ≤ 0.05) and late-treated PA females (P ≤ 0.025) by late-reproductive life. Serum AMH levels positively predicted numbers of total/mature oocytes retrieved, with early-treated PA females having the lowest serum AMH levels, fewest oocytes retrieved and lowest percentage of females with fertilized oocytes that cleaved. CONCLUSIONS Based on these animals, early PA appears to program an exaggerated decline in ovarian reserve with age, suggesting that epigenetically induced hormonal factors during fetal development may influence the cohort size of ovarian follicles after birth. PMID:19740899

  3. Testosterone modulation of anxiety in gonadally-suppressed male rhesus monkeys: a role for gonadotropins?

    PubMed

    Suarez-Jimenez, Benjamin; Gore, Heather E; Hachey, Julie; King, Hanna M; Lacreuse, Agnès

    2013-03-01

    Testosterone (T) has repeatedly been shown to have anxiolytic properties in rodents, but findings in primates are more mixed. To examine the effects of exogenous T on anxiety, we tested pharmacologically-castrated adult male rhesus monkeys in a modified version of the Human Intruder Paradigm, which measured defensive responses to an unfamiliar human staring directly at them for 2 min. Monkeys were tested at 2 week intervals during 4 experimental conditions lasting 4 weeks each: at baseline, during treatment with the gonadotropin releasing hormone (GnRH) agonist leuprolide acetate (200 μg/kg; Lupron phase), during treatment with Lupron+T enanthate (TE, 5 mg/kg; TE phase) and during treatment with Lupron+oil vehicle (oil phase). We found that the number of anxious behaviors was lower during periods of low T (Lupron only and Lupron+oil phases) than during the Lupron+TE phase. No change in pacing or watching behavior was observed. Thus, in contrast to rodent data, we found no evidence for anxiolytic properties of T in male rhesus monkeys. Rather, T supplementation restored baseline levels of anxiety in Lupron-treated monkeys. These discrepant findings may be best explained by the low levels of gonadotropins achieved by the GnRH agonist. We suggest that Lupron-induced luteinizing hormone (LH) suppression reduced anxiety and that this effect was abolished by T administration. This interpretation is consistent with the view that T increases emotional reactivity to a potential threat and facilitates adaptive arousal response in face of immediate social challenge.

  4. Ovarian regulation of kisspeptin neurones in the arcuate nucleus of the rhesus monkey (Macaca mulatta)

    PubMed Central

    Alçin, E.; Sahu, A.; Ramaswamy, S.; Hutz, E.D.; Keen, K.L.; Terasawa, E.; Bethea, C.L.; Plant, T.M.

    2014-01-01

    Tonic gonadotrophin secretion throughout the menstrual cycle is regulated by the negative feedback actions of ovarian oestradiol (E2) and progesterone (P). While kisspeptin neurones in the arcuate nucleus (ARC) of the hypothalamus appear to play a major role in mediating these feedback actions of the steroids in non-primate species, this issue has been less well studied in the monkey. Here, we used immunohistochemistry (IHC) and in situ hybridization (ISH) to examine kisspeptin and KISS1 expression, respectively, in the mediobasal hypothalamus (MBH) of adult ovariectomised (OVX) rhesus monkeys. We also examined kisspeptin expression in the MBH of ovarian intact females, and the effect of E2, P and E2+P replacement on KISS1 expression in OVX animals. Kisspeptin or KISS1 expressing neurons and pronounced kisspeptin fibres were readily identified throughout the ARC of ovariectomised monkeys, but in intact animals on the other hand kisspeptin cell bodies were small in size and number and only fine fibers were observed. Replacement of OVX monkeys with physiologic levels of E2, either alone or with luteal phase levels of P, abolished KISS1 expression in the ARC. Interestingly, P replacement alone for 14 days also resulted in a significant downregulation of KISS1 expression. These findings support the view that, in primates, as in rodents and sheep, kisspeptin signaling in ARC neurones appears to play an important role in mediating the negative feedback action of E2 on gonadotrophin secretion, and indicate a need to further study their regulation by P. PMID:23331967

  5. 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.

  6. Combined unilateral lesions of the amygdala and orbital prefrontal cortex impair affective processing in rhesus monkeys.

    PubMed

    Izquierdo, Alicia; Murray, Elisabeth A

    2004-05-01

    The amygdala and orbital prefrontal cortex (PFo) interact as part of a system for affective processing. To assess whether there is a hemispheric functional specialization for the processing of emotion or reward or both in nonhuman primates, rhesus monkeys (Macaca mulatta) with combined lesions of the amygdala and PFo in one hemisphere, either left or right, were compared with unoperated controls on a battery of tasks that tax affective processing, including two tasks that tax reward processing and two that assess emotional reactions. Although the two operated groups did not differ from each other, monkeys with unilateral lesions, left and right, showed altered reward-processing abilities as evidenced by attenuated reinforcer devaluation effects and an impairment in object reversal learning relative to controls. In addition, both operated groups showed blunted emotional reactions to a rubber snake. By contrast, monkeys with unilateral lesions did not differ from controls in their responses to an unfamiliar human (human "intruder"). Although the results provide no support for a hemispheric specialization of function, they yield the novel finding that unilateral lesions of the amygdala-orbitofrontal cortical circuit in monkeys are sufficient to significantly disrupt affective processing. PMID:14711973

  7. Interactions between Δ(9)-tetrahydrocannabinol and heroin: self-administration in rhesus monkeys.

    PubMed

    Li, Jun-Xu; Koek, Wouter; France, Charles P

    2012-12-01

    The cannabinoid receptor agonist Δ(9)-tetrahydrocannabinol (THC) enhances the antinociceptive effects of µ-opioid receptor agonists, raising the possibility of using a combination of THC and opioids for treating pain. This study examined the effects of noncontingent and contingent administration of THC on intravenous heroin self-administration in rhesus monkeys. Self-administration of different unit doses of heroin (0.0001-0.1 mg/kg/infusion) generated a typical inverted U-shaped dose-response curve. In one experiment (n=4), noncontingent THC (0.1-1.0 mg/kg) dose dependently shifted the heroin dose-response curve downward in three monkeys and slightly leftward in one monkey. In a second experiment (n=4), monkeys could self-administer THC alone (0.0032-0.032 mg/kg/infusion), heroin alone, or a mixture of THC and heroin. THC alone did not maintain responding above that obtained with saline; however, increasing the THC dose with heroin dose dependently decreased the number of infusions received and the rate of responding, as compared with data that were obtained with heroin alone. These results indicate that THC does not significantly enhance the positive reinforcing effects of heroin, further supporting the view that combining cannabinoid and opioid receptor agonists (e.g. for treating pain) does not increase, and might decrease, the abuse liability of individual drugs. PMID:23044830

  8. 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.

  9. 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

    2016-06-01

    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. PMID:26964683

  10. 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 Central

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

    2015-01-01

    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 two 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 three 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. PMID:26322505

  11. 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.

  12. 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…

  13. The strength of the anterior cruciate ligament in humans and Rhesus monkeys.

    PubMed

    Noyes, F R; Grood, E S

    1976-12-01

    The mechanical properties of anterior cruciate bone-ligament-bone specimens from humans and rhesus monkeys were determined in tension to failure under high strain-rate conditions. The age range of the human specimens was from sixteen to eighty-six years. The values fro human specimens obtained from young adults with regard to elastic modulus, ultimate tensile stress, and strain energy to failure were approximately two to three times those for specimens from humans in the sixth decade and older. The major mode of failure was ligament disruption in the specimens from young adult humans and avulsion of bone beneath the ligament insertion site in the specimens from older humans. The difference in mode of failure correlated with histological observations of decreased bone mass at the site of ligament attachment in the specimens from older humans. Rhesus monkey specimens had higher values for elastic modulus, failure stress, and strain energy. Significant reductions in strength and stiffness properties of ligament units were shown to occur with advancing age to a greater degree than expected. All experiments in which specimens from older human cadavera are used should be interpreted with caution when the results are applied to mechanisms of ligament failure for younger or athletic individuals.

  14. OVARIAN RESERVE TESTS AND THEIR UTILITY IN PREDICTING RESPONSE TO CONTROLLED OVARIAN STIMULATION IN RHESUS MONKEYS

    PubMed Central

    Wu, Julie M.; Takahashi, Diana L; Ingram, Donald K.; Mattison, Julie A.; Roth, George; Ottinger, Mary Ann; Zelinski, Mary B.

    2010-01-01

    Controlled ovarian stimulation (COS) is an alternative to natural breeding in nonhuman primates; however, these protocols are costly with no guarantee of success. Toward the objective of predicting COS outcome in rhesus monkeys, the current study evaluated three clinically used ovarian reserve tests (ORTs): day 3 (d3) follicle-stimulating hormone (FSH) with d3 inhibin B (INHB), the clomiphene citrate challenge test (CCCT), and the exogenous FSH Ovarian Reserve Test (EFORT). A COS was also performed and response was classified as either successful (COS+) or unsuccessful (COS−) and retrospectively compared to ORT predictions. FSH and INHB were assessed for best hormonal index in conjunction with the aforementioned tests. INHB was consistently more accurate than FSH in all ORTs used. Overall, a modified version of the CCCT using INHB values yielded the best percentage of correct predictions. This is the first report of ORT evaluation in rhesus monkeys and may provide a useful diagnostic test prior to costly follicle stimulations, as well as predicting the onset of menopause. PMID:20336797

  15. Home cage presentation of complex discrimination tasks to marmosets and rhesus monkeys.

    PubMed

    Crofts, H S; Muggleton, N G; Bowditch, A P; Pearce, P C; Nutt, D J; Scott, E A

    1999-07-01

    The study reported here demonstrates the feasibility of presenting cognitive tests from the Cambridge Neuropsychological Test Automated Battery (CANTAB) to either marmosets or rhesus monkeys in their home cages. This location of testing offers opportunities for the measurement of additional indices, for example spontaneous behaviour (Prowse et al. 1995) and electrophysiology (Pearce et al. 1998) as well as facilitating repeated test presentation. Results from 12 marmosets and 4 rhesus monkeys which have completed several sequences of an eight-stage discrimination task involving simple discriminations, compound discriminations and reversals are reported. The paradigm developed has application in long-term studies. Tests from CANTAB have been used extensively in normal humans (Robbins et al. 1994) as well as a range of patient groups (Owen et al. 1992, Elliott et al. 1995) and to assess drug effects (Coull et al. 1996). Additionally some of these tests have been presented to marmosets (Roberts et al. 1988) to examine neuropsychological functioning. This comparative approach facilitates meaningful cross species comparison, particularly in the study of the effects of pharmacological intervention.

  16. Influence of dietary zinc intake on pregnancy outcome in rhesus monkeys

    SciTech Connect

    Keen. C.L.; Olin, K.L.; Golub, M.S.; Loennerdal, B.; Graham, T.; Gershwin, M.E. )

    1991-03-15

    The authors have reported that when rhesus monkeys are fed marginal Zn diets (MZ) during pregnancy and lactation, their offspring are characterized by altered immune function, growth retardation and behavioral abnormalities; however, these alterations are subtle and neither the mother nor infant develop overt signs of Zn deficiency. They have now studied the effects of feeding a Zn deficient diet (ZD) during pregnancy and lactation. Compared to control and MZ mothers, ZD mothers were characterized by low plasma Zn and developed overt signs of Zn deficiency by the end of pregnancy. At this time serum metallothionein (MT) levels were higher in ZD mothers than in C or MZ mothers. {sup 65}Zn retention from a meal was higher in ZD dams than in C dams, while mitogen response was lower; these data for MZ and D dams were similar. Plasma Zn and mitogen response were lower in ZD than in C infants, with intermediate results in the M infants. {sup 65}Zn retention from a meal was highest in the Zn and lowest in the C infants. Day 30 infant liver Zn levels were similar among the groups; however, MT levels were lower in ZD and MZ infants than in C infants and Fe levels were higher in ZD than in C and MZ infants, These results show that in contrast to the subtle effect of the MZ diet, consumption of ZD diet results in overt signs of Zn deficiency in the adult female rhesus monkey and her infant.

  17. Circadian activity associated with spatial learning and memory in aging rhesus monkeys.

    PubMed

    Haley, G E; Landauer, N; Renner, L; Weiss, A; Hooper, K; Urbanski, H F; Kohama, S G; Neuringer, M; Raber, J

    2009-05-01

    In rodents, spatial learning and memory tests require navigation, whereas in nonhuman primates these tests generally do not involve a navigational component, thus assessing nonhomologous neural systems. To allow closer parallels between rodent and primate studies, we developed a navigational spatial learning and memory task for nonhuman primates and assessed the performance of elderly (19-25 years) female rhesus monkeys (Macaca mulatta). The animals were allowed to navigate in a room containing a series of food ports. After they learned to retrieve food from the ports, a single port was repeatedly baited and the animals were tested until they learned the correct location. The location of the baited port was then changed (shift position). We also determined whether test performance was associated with circadian activity measured with accelerometers. Performance measures included trials to criterion, search strategies, and several indices of circadian activity. Animals learned the task as reflected in their search strategies. Correlations were found between the number of initial or shift trials and circadian activity parameters including day activity, dark:light activity ratio, sleep latency, and wake bouts. Thus, disruptions in circadian rhythms in nonhuman primates are associated with poorer performance on this novel test. These data support the usefulness of this spatial navigational test to assess spatial learning and memory in rhesus monkeys and the importance of circadian activity in performance.

  18. Exposure to sunlight reduces the risk of myopia in rhesus monkeys.

    PubMed

    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

  19. 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

  20. 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

  1. 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…

  2. Effects of prenatal androgens on rhesus monkeys: A model system to explore the organizational hypothesis in primates

    PubMed Central

    Thornton, Jan; Zehr, Julia L.; Loose, Michael D.

    2011-01-01

    After proposing the organizational hypothesis from research in prenatally androgenized guinea pigs (Phoenix et al., 1959), the same authors almost immediately extended the hypothesis to a nonhuman primate model, the rhesus monkey. Studies over the last 50 years have verified that prenatal androgens have permanent effects in rhesus monkeys on the neural circuits that underlie sexually dimorphic behaviors. These behaviors include both sexual and social behaviors, all of which are also influenced by social experience. Many juvenile behaviors such as play and mounting are masculinized, and aspects of adult sexual behavior are both masculinized (e.g. approaches, sex contacts, and mounts) and defeminized (e.g. sexual solicits). Different behavioral endpoints have different periods of maximal susceptibility to the organizing actions of prenatal androgens. Aromatization is not important, as both testosterone and dihydrotestosterone are equally effective in rhesus monkeys. Although the full story of the effects of prenatal androgens on sexual and social behaviors in the rhesus monkey has not yet completely unfolded, much progress has been made. Amazingly, a large number of the inferences drawn from the original 1959 study have proved applicable to this nonhuman primate model. PMID:19446080

  3. Environmental Control, Social Context, and Individual Differences in Behavioral and Cortisol Responses to Novelty in Infant Rhesus Monkeys

    ERIC Educational Resources Information Center

    Roma, Peter G.; Champoux, Maribeth; Suomi, Stephen J.

    2006-01-01

    The effects of appetitive controllability on behavioral and cortisol reactivity to novelty in 12 infant rhesus monkeys were studied. Surrogate-peer-reared infants had homecage access to food treats contingently via lever pressing ("master") or noncontingently ("yoked") for 12 weeks from postnatal month 2. Masters lever-pressed more, but did not…

  4. Rhesus Monkeys (Macaca mulatta) and Capuchin Monkeys (Cebus apella) Remember Future Responses in a Computerized Task

    PubMed Central

    Beran, Michael J.; Evans, Theodore A.; Klein, Emily D.; Einstein, Gilles O.

    2012-01-01

    Planning is an important aspect of many daily activities for humans. Planning involves forming a strategy in anticipation of a future need. However, evidence that nonhuman animals can plan for future situations is limited, particularly in relation to the many other kinds of cognitive capacities that they appear to share with humans. One critical aspect of planning is the ability to remember future responses, or what is called prospective coding. Two monkey species performed a series of computerized tasks that required encoding a future response at the outset of each trial. Monkeys of both species showed competence in all tests that were given, providing evidence that they anticipated future responses, and that they appropriately engaged in those responses when the time was right for such responses. In addition, some tests demonstrated that monkeys even remembered future responses that were not as presently motivating as were other aspects of the task environment. These results indicated that monkeys can anticipate future responses and retain and implement those responses when appropriate. PMID:22545901

  5. Effect of mother's dominance rank on offspring temperament in infant rhesus monkeys (Macaca mulatta).

    PubMed

    Suarez-Jimenez, Benjamin; Hathaway, Amanda; Waters, Carlos; Vaughan, Kelli; Suomi, Stephen J; Noble, Pamela L; Pine, Daniel S; Fox, Nathan A; Nelson, Eric E

    2013-01-01

    In humans, temperament plays an important role in socialization and personality. Some temperaments, such as behavioral inhibition are associated with an increased risk for psychopathology. Nonhuman primates can serve as a model for neurobiological and developmental contributions to emotional development and several recent studies have begun to investigate temperament in nonhuman primates. In rhesus monkeys, dominance rank is inherited from the mother and is associated with social and emotional tendencies that resemble differences in temperament. The current study assessed differences in temperament in infant rhesus monkeys as a function of maternal dominance rank. Temperament was assessed in 26 infants (13 males) from birth until 6 months of age with a battery that included Brazelton test, human intruder test, human intruder-startle, cortisol stress reactivity, and home cage observations of interactions with peers and the mother. Throughout testing, infants lived with their mothers and a small group of other monkeys in indoor/outdoor runs. Dominance rank of the mothers within each run was rated as either low/middle (N = 18, 9 male) or high/alpha (N = 8, 4 female). Infants of high-ranking mothers displayed more intruder-directed aggression and reduced startle potentiation in the human intruder tests. Dominant offspring also had reduced levels cortisol and startle across development and spent more time away from mothers in the interaction tests. These results suggest that dominance of the mother may be reflected in behavioral reactivity of infants early in life. These findings set up future studies, which may focus on contributing factors to both dominance and temperament such as genetics, rearing, and socialization. Such factors are likely to interact across development in meaningful ways. These results also suggest future human-based studies of a similar relationship may be warranted, although social dominance is clearly more complex in human than macaque societies.

  6. 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.

  7. 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

  8. Pharmacokinetics of repeated doses of intravenous cocaine across the menstrual cycle in rhesus monkeys.

    PubMed

    Evans, Suzette M; Foltin, Richard W

    2006-01-01

    Numerous studies in rodents suggest that there are sex differences in response to cocaine that are related to fluctuations in the ovarian hormones of females. Given that female rhesus monkeys have menstrual cycles that are remarkably similar to those of humans, they provide an ideal laboratory animal model for assessing the effects of cocaine across the menstrual cycle. The present study assessed the effects of 4 injections of intravenous (i.v.) cocaine (0.00, 0.25 or 0.50 mg/kg), spaced 15 min apart, in 4 female rhesus monkeys. Each monkey was tested with each dose during 4 phases of the menstrual cycle: menses, midfollicular, periovulatory and midluteal. Estradiol and progesterone levels were measured each session before cocaine administration to verify phase of the menstrual cycle. Cocaine and cocaine metabolite levels were measured 5 min after each cocaine dose and 5, 15, 30, 45, 60 and 120 min after the last cocaine dose. Similarly, levels of luteinizing hormone (LH) and prolactin levels were measured before, 5, 15, 30, 45, 60 and 120 min after the last cocaine dose. Cocaine and metabolite levels increased as a function of dose, but there were minimal differences across the menstrual cycle following repeated injections of cocaine. With a few exceptions, LH levels decreased as a function of time within the session, with no differences as a function of cocaine dose. Cocaine produced transient increases in LH levels during the luteal phase, with maximal levels occurring after the second cocaine injection. Lastly, cocaine substantially decreased prolactin levels across all menstrual cycle phases. Taken together, these data indicate that any behavioral differences observed either across the menstrual cycle or between males and females, are probably not related to alterations in the pharmacokinetics of cocaine across the menstrual cycle. PMID:16426669

  9. Effects of varenicline on the reinforcing and discriminative stimulus effects of cocaine in rhesus monkeys.

    PubMed

    Gould, Robert W; Czoty, Paul W; Nader, Susan H; Nader, Michael A

    2011-11-01

    Varenicline is a low-efficacy, α4β2* subtype-selective nicotinic acetylcholine receptor (nAChR) agonist that has shown success in smoking cessation and promise in preclinical assessments relating to other drugs of abuse. The primary goal of the present study was to examine the effects of varenicline on cocaine self-administration and cocaine discrimination and compare these effects with those of the nAChR agonist nicotine and antagonist mecamylamine. One limitation of agonist treatments is the potential for abuse. Thus, a second goal was to examine the abuse potential of varenicline in rhesus monkeys. In the first experiment, rhesus monkeys (n = 3) were trained to self-administer cocaine (saline, 0.01-0.56 mg/kg) under a progressive-ratio schedule of reinforcement; monkeys also earned all of their food by responding on another lever under a fixed-ratio 50 schedule of reinforcement. Chronic administration of varenicline (0.01-0.56 mg/kg p.o., salt) potentiated the reinforcing effects of cocaine, whereas mecamylamine (0.3-1.7 mg/kg p.o, i.m., i.v., salt) had no significant effects on cocaine self-administration up to doses that disrupted food-maintained responding. Neither varenicline (0.01-0.17 mg/kg, salt) nor nicotine (0.01-0.1 mg/kg, base) functioned as reinforcers when substituted for cocaine. Finally, in monkeys trained to discriminate self-administered 0.3 mg/kg cocaine, varenicline (0.1-0.3 mg/kg i.v.) did not substitute for cocaine but, along with mecamylamine (0.3-1.7 mg/kg i.v.) and nicotine (0.03-0.1 mg/kg i.v.), potentiated the discriminative stimulus effects of cocaine. These results suggest that varenicline has low abuse liability in monkey models of cocaine abuse, but would not be an effective medication for cocaine addiction. PMID:21856860

  10. Effects of negative punishment contingencies on cocaine self-administration by rhesus monkeys.

    PubMed

    Nader, M A; Morgan, D

    2001-04-01

    Although punishment contingencies are widely used with human drug users, basic research on the effectiveness of these procedures is limited. The present study evaluated the effects of a negative punishment contingency, response-contingent timeout (TO) presentation, on cocaine-maintained responding. Rhesus monkeys were trained under a multiple fixed-interval (FI) 5-min cocaine, conjoint FI 5-min cocaine, variable-interval (VI) 30-sec TO schedule. TO values were either 0 (baseline), 10, 30, or 60s in length. During the TO periods, the FI clock continued to operate but the discriminative stimuli signaling cocaine availability were removed, and responding had no scheduled consequence. Cocaine maintained responding in all monkeys and the dose-effect curve was characterized as an inverted U-shaped function. The response-contingent TO presentations reduced response rates maintained by cocaine in all monkeys compared to baseline. The magnitude of the reduction in response rates was not a function of the length of the TO period (i.e. intensity of the punisher), and the punishment effect was enhanced by increases in cocaine dose. When responding was punished, response rates in the unpunished components either also decreased (i.e. response induction; approximately 30% of the cases) or were not affected (approximately 60%). These results demonstrate that cocaine-maintained behavior can be decreased by environmental manipulations involving negative punishment contingencies. PMID:11396521

  11. Pharmacokinetics of isoflavones from soy infant formula in neonatal and adult rhesus monkeys.

    PubMed

    Doerge, Daniel R; Woodling, Kellie A; Churchwell, Mona I; Fleck, Stefanie C; Helferich, William G

    2016-06-01

    Consumption of soy infant formula represents a unique exposure scenario in which developing children ingest a mixture of endocrine-active isoflavones along with a substantial portion of daily nutrition. Genistein and daidzein were administered as glucoside conjugates to neonatal rhesus monkeys in a fortified commercial soy formula at 5, 35, and 70 days after birth. A single gavage dosing with 10 mg/kg bw genistein and 6 mg/kg bw daidzein was chosen to represent the upper range of typical daily consumption and to facilitate complete pharmacokinetic measurements for aglycone and total isoflavones and equol. Adult monkeys were also gavaged with the same formula solution at 2.8 and 1.6 mg/kg bw genistein and daidzein, respectively, and by IV injection with isoflavone aglycones (5.2 and 3.2 mg/kg bw, respectively) to determine absolute bioavailability. Significant differences in internal exposure were observed between neonatal and adult monkeys, with higher values for dose-adjusted AUC and Cmax of the active aglycone isoflavones in neonates. The magnitude and frequency of equol production by the gut microbiome were also significantly greater in adults. These findings are consistent with immaturity of metabolic and/or physiological systems in developing non-human primates that reduces total clearance of soy isoflavones from the body. PMID:27084109

  12. Acquisition of cocaine self-administration with unsignaled delayed reinforcement in rhesus monkeys.

    PubMed

    Galuska, Chad M; Woods, James H

    2005-09-01

    Six experimentally naive rhesus monkeys produced 0.01 mg/kg/infusion cocaine by lever pressing under a tandem fixed-ratio 1 differential-reinforcement-of-other-behavior schedule. One lever press initiated an unsignaled 15- or 30-s delay culminating in cocaine delivery. Each press made during the delay reset the delay interval. With two exceptions, responding was acquired and maintained at higher rates than responding on a second (inoperative) lever. For the exceptions, a cancellation contingency was arranged in which each formerly inoperative-lever response reset the tandem schedule. This manipulation reduced presses on the inoperative lever. Subsequently, the consequences of responding on the two levers were reversed, and the monkeys again responded at higher rates on the operative lever. As a comparison, 3 additional experimentally naive monkeys received response-independent cocaine deliveries. Although lever pressing was observed, it extinguished and was subsequently reestablished under the tandem schedule. The results suggest that although response-reinforcer contiguity is not required for cocaine to acquire reinforcing functions, a response-reinforcer relation appears necessary. PMID:16262189

  13. 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.

  14. Depletion of the spermatogonia from the seminiferous epithelium of the rhesus monkey after X irradiation

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

    1988-03-01

    In unirradiated testes large differences were found in the total number of spermatogonia among different monkeys, but the number of spermatogonia in the right and the left testes of the same monkey appeared to be rather similar. During the first 11 days after irradiation with 0.5 to 4.0 Gy of X rays the number of Apale spermatogonia (Ap) decreased to about 13% of the control level, while the number of Adark spermatogonia (Ad) did not change significantly. A significant decrease in the number of Ad spermatogonia was seen at Day 14 together with a significant increase in the number of Ap spermatogonia. It was concluded that the resting Ad spermatogonia are activated into proliferating Ap spermatogonia. After Day 16 the number of both Ap and Ad spermatogonia decreased to low levels. Apparently the new Ap spermatogonia were formed by lethally irradiated Ad spermatogonia and degenerated while attempting to divide. The activation of the Ad spermatogonia was found to take place throughout the cycle of the seminiferous epithelium. Serum FSH, LH, and testosterone levels were measured before and after irradiation. Serum FSH levels already had increased during the first week after irradiation to 160% of the control level. Serum LH levels increased between 18 and 25 days after irradiation. Serum testosterone levels did not change at all. The results found in the rhesus monkey are in line with those found in humans, but due to the presence of Ad spermatogonia they differ from those obtained in non-primates.

  15. Age-Related Cognitive Deficits In Rhesus Monkeys Mirror Human Deficits on an Automated Test Battery

    PubMed Central

    Nagahara, Alan H.; Bernot, Tim; Tuszynski, Mark H.

    2010-01-01

    Aged non-human primates are a valuable model for gaining insight into mechanisms underlying neural decline with aging and during the course of neurodegenerative disorders. Behavioral studies are a valuable component of aged primate models, but are difficult to perform, time consuming, and often of uncertain relevance to human cognitive measures. We now report findings from an automated cognitive test battery in aged primates using equipment that is identical, and tasks that are similar, to those employed in human aging and Alzheimer’s disease studies. Young (7.1 ± 0.8 years) and aged (23.0 ± 0.5 years) rhesus monkeys underwent testing on a modified version of the Cambridge Automated Neuropsychological Test Battery (CANTAB), examining cognitive performance on separate tasks that sample features of visuospatial learning, spatial working memory, discrimination learning, and skilled motor performance. We find selective cognitive impairments among aged subjects in visuospatial learning and spatial working memory, but not in delayed recall of previously learned discriminations. Aged monkeys also exhibit slower speed in skilled motor function. Thus, aged monkeys behaviorally characterized on a battery of automated tests reveal patterns of age-related cognitive impairment that mirror in quality and severity those of aged humans, and differ fundamentally from more severe patterns of deficits observed in Alzheimer’s Disease. PMID:18760505

  16. Discriminative and reinforcing stimulus effects of nicotine, cocaine, and cocaine + nicotine combinations in rhesus monkeys.

    PubMed

    Mello, Nancy K; Newman, Jennifer L

    2011-06-01

    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 twofold: 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

  17. Effects of vestibular prosthesis electrode implantation and stimulation on hearing in rhesus monkeys.

    PubMed

    Dai, Chenkai; Fridman, Gene Y; Della Santina, Charles C

    2011-07-01

    To investigate the effects of vestibular prosthesis electrode implantation and activation on hearing in rhesus monkeys, we measured auditory brainstem responses (ABR) and distortion product otoacoustic emissions (DPOAE) in four rhesus monkeys before and after unilateral implantation of vestibular prosthesis electrodes in each of 3 left semicircular canals (SCC). Each of the 3 left SCCs were implanted with electrodes via a transmastoid approach. Right ears, which served as controls, were not surgically manipulated. Hearing tests were conducted before implantation (BI) and then 4 weeks post-implantation both without electrical stimulation (NS) and with electrical stimulation (S). During the latter condition, prosthetic electrical stimuli encoding 3 dimensions of head angular velocity were delivered to the 3 ampullary branches of the left vestibular nerve via each of 3 electrode pairs of a multichannel vestibular prosthesis. Electrical stimuli comprised charge-balanced biphasic pulses at a baseline rate of 94 pulses/s, with pulse frequency modulated from 48 to 222 pulses/s by head angular velocity. ABR hearing thresholds to clicks and tone pips at 1, 2, and 4 kHz increased by 5-10 dB from BI to NS and increased another ∼5 dB from NS to S in implanted ears. No significant change was seen in right ears. DPOAE amplitudes decreased by 2-14 dB from BI to NS in implanted ears. There was a slight but insignificant decrease of DPOAE amplitude and a corresponding increase of DPOAE/Noise floor ratio between NS and S in implanted ears. Vestibular prosthesis electrode implantation and activation have small but measurable effects on hearing in rhesus monkeys. Coupled with the clinical observation that patients with cochlear implants only rarely exhibit signs of vestibular injury or spurious vestibular nerve stimulation, these results suggest that although implantation and activation of multichannel vestibular prosthesis electrodes in human will carry a risk of hearing loss

  18. Indirect assessment of pulsatile gonadotropin-releasing hormone release in agonadal prepubertal rhesus monkeys (Macaca mulatta).

    PubMed

    Suter, K J; Pohl, C R; Plant, T M

    1999-01-01

    The major purpose of this study was to characterize the open-loop frequency of pulsatile GnRH release in the female rhesus monkey at an age (15-20 months) when the prepubertal restraint on the hypothalamic-pituitary axis is maximally imposed. Additionally, evidence for pulsatile GnRH release in agonadal males of comparable age was also sought. Episodic LH secretion from the pituitary was used as an indirect index of GnRH discharges. In order to maximize the sensitivity of this in situ bioassay, the responsiveness of the pituitary gonadotrophs was usually first heightened by an i.v. intermittent infusion of the synthetic peptide. Monkeys (five females, three males) were castrated between 9 and 14 months of age, implanted with indwelling venous catheters, fitted with nylon jackets and housed in specialized cages that permitted remote access to the venous circulation with minimal restraint and without interruption of the light-darkness cycle. In females, LH secretion was generally assessed at 20-day intervals during alternate nighttime (1900-0200 h) and daytime (0700-1400 h) windows. In males, LH was assessed less frequently and only at night. The mean frequency of pulsatile LH release in agonadal prepubertal females was 4 pulses/7 h during the night and 2 pulses/7 h during the day. These findings indicate that, prior to puberty in the female monkey, the GnRH pulse generator operates at a relatively slow frequency and is subjected to diurnal modulation. In males, evidence for robust pulsatile GnRH release was not observed. The striking difference in activity of the GnRH pulse generator in agonadal prepubertal male and female monkeys reinforces the view that the ontogeny of the hypothalamic drive to the pituitary-gonadal axis in higher primates, including man, is sexually differentiated.

  19. 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.

  20. In vivo comparison of the reinforcing and dopamine transporter effects of local anesthetics in rhesus monkeys.

    PubMed

    Wilcox, Kristin M; Kimmel, Heather L; Lindsey, Kimberly P; Votaw, John R; Goodman, Mark M; Howell, Leonard L

    2005-12-15

    Dopaminergic mechanisms are thought to play a central role in the reinforcing effects of cocaine. Similar to cocaine, other local anesthetics bind to the dopamine transporter (DAT) and inhibit DA uptake in rodent and monkey brain. Additionally, local anesthetics are self-administered in rhesus monkeys, indicative of abuse liability. The present study examined the reinforcing and DAT effects of the local anesthetics dimethocaine, procaine and cocaine using in vivo techniques. Monkeys were trained to respond under a second-order schedule for i.v. cocaine administration (0.10 or 0.30 mg/kg/infusion). When responding was stable, dimethocaine (0.030-1.7 mg/kg/ infusion) or procaine (0.10-10 mg/kg/ infusion) was substituted for the cocaine training dose. Dimethocaine administration produced higher response rates compared with that of procaine, and was a more potent reinforcer. Drug effects on behavior were related to DAT occupancy in monkey striatum during neuroimaging with positron emission tomography (PET). DAT occupancy was determined by displacement of 8-(2-[(18)F]fluroethyl)2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane (FECNT). DAT occupancy was between 66 and 82% and <10-41% for doses of dimethocaine and procaine that maintained maximum response rates, respectively. Finally, in vivo microdialysis in awake subjects determined drug-induced changes in extracellular DA in the caudate nucleus. There was close correspondence between peak increases in DA and DAT occupancy. Overall, reinforcing effects were consistent with DAT effects determined with in vivo techniques. The results further support a role for the DAT in the abuse liability of local anesthetics. PMID:16206183

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

    SciTech Connect

    Patterson, Tucker A.; Twaddle, Nathan C.; Roegge, Cindy S.; Callicott, Ralph J.; Fisher, Jeffrey W.; Doerge, Daniel R.

    2013-02-15

    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) were 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 measurements.

  2. 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. PMID:26534942

  3. Is radiation-induced ovarian failure in rhesus monkeys preventable by luteinizing hormone-releasing hormone agonists?: Preliminary observations

    SciTech Connect

    Ataya, K.; Pydyn, E.; Ramahi-Ataya

    1995-03-01

    With the advent of cancer therapy, increasing numbers of cancer patients are achieving long term survival. Impaired ovarian function after radiation therapy has been reported in several studies. Some investigators have suggested that luteinizing hormone-releasing hormone agonists (LHRHa) can prevent radiation-induced ovarian injury in rodents. Adult female rhesus monkeys were given either vehicle or Leuprolide acetate before, during, and after radiation. Radiation was given in a dose of 200 rads/day for a total of 4000 rads to the ovaries. Frequent serum samples were assayed for estradiol (E{sub 2}) and FSH. Ovariectomy was performed later. Ovaries were processed and serially sectioned. Follicle count and size distribution were determined. Shortly after radiation started, E{sub 2} dropped to low levels, at which it remained, whereas serum FSH level, which was low before radiation, rose soon after starting radiation. In monkeys treated with a combination of LHRHa and radiation, FSH started rising soon after the LHRHa-loaded minipump was removed (after the end of radiation). Serum E{sub 2} increased after the end of LHRHa treatment in the non-irradiated monkey, but not in the irradiated monkey. Follicle counts were not preserved in the LHRHa-treated monkeys that received radiation. The data demonstrated no protective effect of LHRHa treatment against radiation-induced ovarian injury in this rhesus monkey model. 58 refs., 2 figs., 1 tab.

  4. Gustatory responses in the nucleus tractus solitarius of the alert cynomolgus monkey.

    PubMed

    Scott, T R; Yaxley, S; Sienkiewicz, Z J; Rolls, E T

    1986-01-01

    Multiunit and single neuron responses to taste stimuli in the nucleus tractus solitarius (NTS) of alert cynomolgus monkeys were analyzed. Intensity-response functions, including neural thresholds to glucose and quinine HCl, agreed well with psychophysical reports, implying that the cynomolgus monkey and human share the same dynamic range of sensitivity to prototypical taste stimuli. The NTS is chemotopically organized: neurons most responsive to HCl are more common in the posterior gustatory area, whereas those most responsive to glucose and NaCl are located in the anterior NTS. Responsiveness to quinine is more widely distributed but tends toward the anterior. Efforts were made to determine if neurons could be divided into a discrete number of types, as determined by their sensitivities to the prototypical stimuli. The clearest distinction was between those that did or did not respond well to HCl. Beyond this, neuronal categories were not obvious. Individual neurons were quite broadly sensitive to our stimulus array, so that, for the typical NTS cell, no one of the four prototypes evoked a majority of the discharges. This extreme breadth of tuning suggests that taste-quality information in the monkey might be incorporated in relative discharge rates across the neuron population. Correlations among patterns of activity to the four prototypical stimuli indicated that only HCl and quinine HCl have closely related taste qualities.

  5. Sequence of the rhesus monkey T-cell receptor {beta} chain diversity and joining loci

    SciTech Connect

    Cheynier, R.; Henrichwark, S.; Wain-Hobson, S.

    1996-06-01

    Rhesus monkeys are frequently used as animal models for human diseases, most noticeably for simian immunodeficiency virus (SIV) infection and simian AIDS. An analysis of HIV proviruses and HIV-specific cytotoxic T cells in splenic white pulps relied heavily on the analysis of rearranged TCRBV sequences. The spleens were derived from patients with drug-insensitive idiopathic thrombocytopenia purpura and frequently taken at an advanced stage of disease. In order to obtain some insight into the balance of forces between the virus and the immune system during earlier stages of infection, one must inevitably turn to the SIV/macaque AIDS model. As a prerequisite to undertaking similar virological and immunological studies the nucleotide sequence of the macaque TCRBJ loci had to be established. 9 refs., 4 figs., 1 tab.

  6. The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala.

    PubMed

    Grayson, David S; Bliss-Moreau, Eliza; Machado, Christopher J; Bennett, Jeffrey; Shen, Kelly; Grant, Kathleen A; Fair, Damien A; Amaral, David G

    2016-07-20

    Contemporary research suggests that the mammalian brain is a complex system, implying that damage to even a single functional area could have widespread consequences across the system. To test this hypothesis, we pharmacogenetically inactivated the rhesus monkey amygdala, a subcortical region with distributed and well-defined cortical connectivity. We then examined the impact of that perturbation on global network organization using resting-state functional connectivity MRI. Amygdala inactivation disrupted amygdalocortical communication and distributed corticocortical coupling across multiple functional brain systems. Altered coupling was explained using a graph-based analysis of experimentally established structural connectivity to simulate disconnection of the amygdala. Communication capacity via monosynaptic and polysynaptic pathways, in aggregate, largely accounted for the correlational structure of endogenous brain activity and many of the non-local changes that resulted from amygdala inactivation. These results highlight the structural basis of distributed neural activity and suggest a strategy for linking focal neuropathology to remote neurophysiological changes.

  7. 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.

  8. [The effect of adrafinil on the nocturnal activity of the rhesus monkey (Macaca mulatta)].

    PubMed

    Milhaud, C L; Klein, M J

    1985-01-01

    The nocturnal activity of a primate was used as an evaluation criterium for a stimulating substance: adrafinil (CRL 40028). Ten rhesus monkeys were placed in a controlled environment and their activity was measured, in relative time, using an ultra-sound system. The animals repeatedly received 60, 90 and 120 mg X kg-1 adrafinil per os. Globally, the dose of 60 mg X kg-1 doubled the animals' nocturnal activity whereas 90 and 120 mg X kg-1 increased it fourfold, the activity level becoming practically identical to diurnal activity. The effects of 60 mg X kg-1 were only significant after the second treatment whereas doses of 90 and 120 mg X kg-1 were already significantly efficient after the first administration. A stimulating effect persisted approximately 36 hrs after the second treatment with 90 or 120 mg X kg-1. No sedative effect of recovery was observed during the posttreatment phase. PMID:4094435

  9. Wild dengue virus types 1, 2 and 3 viremia in rhesus monkeys.

    PubMed

    Freire, M S; Marchevsky, R S; Almeida, L F C; Yamamura, A M Y; Caride, E C; Brindeiro, P A; Motta, M C A; Nogueira, R M R; Kubelka, C F; Bonaldo, M C; Galler, R

    2007-05-01

    Among the flaviviruses, dengue, with its four serotypes, has spread throughout the tropics. The most advanced vaccines developed so far include live attenuated viruses, which have been tested in humans but none has been licensed. Preclinical testing of dengue vaccine candidates is performed initially in mice and in nonhuman primates. In the latter the main criteria used to assay protection are neutralizing antibodies elicited by the vaccine candidate and the magnitude and duration of peripheral viremia upon challenge of previously immunized animals. Towards the identification of wild-type viruses that could be used in challenge experiments a total of 31 rhesus monkeys were inoculated subcutaneously of wild dengue types 1, 2, and 3 viruses. The viremia caused by the different viruses was variable but it was possible to identify dengue viruses useful as challenge strains.

  10. The Rhesus Monkey Connectome Predicts Disrupted Functional Networks Resulting from Pharmacogenetic Inactivation of the Amygdala.

    PubMed

    Grayson, David S; Bliss-Moreau, Eliza; Machado, Christopher J; Bennett, Jeffrey; Shen, Kelly; Grant, Kathleen A; Fair, Damien A; Amaral, David G

    2016-07-20

    Contemporary research suggests that the mammalian brain is a complex system, implying that damage to even a single functional area could have widespread consequences across the system. To test this hypothesis, we pharmacogenetically inactivated the rhesus monkey amygdala, a subcortical region with distributed and well-defined cortical connectivity. We then examined the impact of that perturbation on global network organization using resting-state functional connectivity MRI. Amygdala inactivation disrupted amygdalocortical communication and distributed corticocortical coupling across multiple functional brain systems. Altered coupling was explained using a graph-based analysis of experimentally established structural connectivity to simulate disconnection of the amygdala. Communication capacity via monosynaptic and polysynaptic pathways, in aggregate, largely accounted for the correlational structure of endogenous brain activity and many of the non-local changes that resulted from amygdala inactivation. These results highlight the structural basis of distributed neural activity and suggest a strategy for linking focal neuropathology to remote neurophysiological changes. PMID:27477019

  11. EV71-infected CD14(+) cells modulate the immune activity of T lymphocytes in rhesus monkeys.

    PubMed

    Wang, Jingjing; Pu, Jing; Huang, Hongtai; Zhang, Ying; Liu, Longding; Yang, Erxia; Zhou, Xiaofang; Ma, Na; Zhao, Hongling; Wang, Lichun; Xie, Zhenfeng; Tang, Donghong; Li, Qihan

    2013-07-01

    Preliminary studies of the major pathogen enterovirus 71 (EV71), a member of the Picornaviridae family, have suggested that EV71 may be a major cause of fatal hand, foot and mouth disease cases. Currently, the role of the pathological changes induced by EV71 infection in the immunopathogenic response remains unclear. Our study focused on the interaction between this virus and immunocytes and indicated that this virus has the ability to replicate in CD14(+) cells. Furthermore, these EV71-infected CD14(+) cells have the capacity to stimulate the proliferation of T cells and to enhance the release of certain functional cytokines. An adaptive immune response induced by the back-transfusion of EV71-infected CD14(+) cells was observed in donor neonatal rhesus monkeys. Based on these observations, the proposed hypothesis is that CD14(+) cells infected by the EV71 virus might modulate the anti-EV71 adaptive immune response by inducing simultaneous T-cell activation.

  12. 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. PMID:27479072

  13. 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

  14. 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.

  15. Immunization of simian immunodeficiency virus-infected rhesus monkeys with soluble human CD4 elicits an antiviral response.

    PubMed Central

    Watanabe, M; Levine, C G; Shen, L; Fisher, R A; Letvin, N L

    1991-01-01

    Since the CD4 molecule is a high-affinity cell-surface receptor for the human immunodeficiency virus (HIV), it has been suggested that a soluble truncated form of CD4 may compete with cell-surface CD4 for HIV binding and thus be of use in the therapy of AIDS. We have utilized the simian immunodeficiency virus of macaques (SIVmac)-infected rhesus monkeys to explore another possible therapeutic application of CD4 in AIDS--the use of recombinant soluble CD4 (rsCD4) as an immunogen. SIVmac-infected rhesus monkeys immunized with human rsCD4 developed not only an anti-human CD4 but also an anti-rhesus monkey CD4 antibody response. Coincident with the generation of this antibody response, SIVmac could not be isolated easily from peripheral blood lymphocytes and bone marrow macrophages of these animals. Furthermore, the decreased number of both granulocyte/macrophage and erythrocyte colonies grown from the bone marrow of these immunized monkeys rose to normal levels. These findings suggest that a modified human CD4 molecule serving as an immunogen might elicit an antibody response in man that could induce a beneficial therapeutic response in HIV-infected individuals. PMID:2052546

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

    SciTech Connect

    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 virus 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.

  17. Neonatal amygdala lesions alter basal cortisol levels in infant rhesus monkeys

    PubMed Central

    Raper, Jessica; Bachevalier, Jocelyne; Wallen, Kim; Sanchez, Mar

    2012-01-01

    The amygdala is mostly thought to exert an excitatory influence on the hypothalamic-pituitary-adrenal (HPA) axis, although its role regulating HPA basal tone is less clear, particularly during primate development. The current study examined the effects of neonatal amygdala lesions on basal HPA function and the postnatal testosterone (T) surge of rhesus monkeys reared with their mothers in large outdoor social groups. An early morning basal blood sample was collected at 2.5 months of age, whereas at 5 months samples were collected not only at sunrise, but also at mid-day and sunset to examine the diurnal rhythm of cortisol. At 2.5 months of age sham-operated males exhibited higher cortisol than females, but this sex difference was abolished by neonatal amygdalectomy, with lesioned males also showing lower basal cortisol than controls. Although neonatal amygdalectomy did not alter the postnatal T surge, there was a positive relationship between T and basal cortisol levels. At 5 months of age, neither the sex difference in cortisol, nor its correlation with T levels were apparent any longer. Instead, the diurnal cortisol rhythm of both males and females with amygdalectomy showed a blunted decline from mid-day to sunset compared to controls. These results indicate that neonatal amygdala damage alters basal HPA function in infant rhesus monkeys, affecting males only at early ages (at 2.5 months), while leaving the postnatal T surge intact, and resulting in a flattened diurnal rhythm in both genders at the later ages. Thus, the primate amygdala has a critical influence on the HPA axis in the first few months of life. PMID:23159012

  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 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.

  20. 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.

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

    PubMed

    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

    2013-08-01

    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 subcellular 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 subcellular 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 reflects 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

  2. RL-37, an alpha-helical antimicrobial peptide of the rhesus monkey.

    PubMed

    Zhao, C; Nguyen, T; Boo, L M; Hong, T; Espiritu, C; Orlov, D; Wang, W; Waring, A; Lehrer, R I

    2001-10-01

    Rhesus monkey bone marrow expresses a cathelicidin whose C-terminal domain comprises a 37-residue alpha-helical peptide (RL-37) that resembles human LL-37. Like its human counterpart, RL-37 rapidly permeabilized the membranes of Escherichia coli ML-35p and lysed liposomes that simulated bacterial membranes. When tested in media whose NaCl concentrations approximated those of extracellular fluids, RL-37 was considerably more active than LL-37 against staphylococci. Whereas human LL-37 contains five acidic residues and has a net charge of +6, rhesus RL-37 has only two acidic residues and a net charge of +8. Speculating that the multiple acidic residues of human LL-37 reduced its efficacy against staphylococci, we made a peptide (LL-37 pentamide) in which each aspartic acid of LL-37 was replaced by an asparagine and each glutamic acid was replaced by a glutamine. LL-37 pentamide's antistaphylococcal activity was substantially greater than that of LL-37. Thus, although the precursor of LL-37 is induced in human skin keratinocytes by injury or inflammation, its insufficiently cationic antimicrobial domain may contribute to the success of staphylococci in colonizing and infecting human skin.

  3. 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.

  4. Rhesus monkey embryos produced by nuclear transfer from embryonic blastomeres or somatic cells.

    PubMed

    Mitalipov, Shoukhrat M; Yeoman, Richard R; Nusser, Kevin D; Wolf, Don P

    2002-05-01

    Production of genetically identical nonhuman primates would reduce the number of animals required for biomedical research and dramatically impact studies pertaining to immune system function, such as development of the human-immunodeficiency-virus vaccine. Our long-term goal is to develop robust somatic cell cloning and/or twinning protocols in the rhesus macaque. The objective of this study was to determine the developmental competence of nuclear transfer (NT) embryos derived from embryonic blastomeres (embryonic cell NT) or fetal fibroblasts (somatic cell NT) as a first step in the production of rhesus monkeys by somatic cell cloning. Development of cleaved embryos up to the 8-cell stage was similar among embryonic and somatic cell NT embryos and comparable to controls created by intracytoplasmic sperm injection (ICSI; mean +/- SEM, 81 +/- 5%, 88 +/- 7%, and 87 +/- 4%, respectively). However, significantly lower rates of development to the blastocyst stage were observed with somatic cell NT embryos (1%) in contrast to embryonic cell NT (34 +/- 15%) or ICSI control embryos (46 +/- 6%). Development of somatic cell NT embryos was not markedly affected by donor cell treatment, timing of activation, or chemical activation protocol. Transfer of embryonic, but not of somatic cell NT embryos, into recipients resulted in term pregnancy. Future efforts will focus on optimizing the production of somatic cell NT embryos that develop in high efficiency to the blastocyst stage in vitro.

  5. Rhesus monkey model of liver disease reflecting clinical disease progression and hepatic gene expression analysis.

    PubMed

    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

    2015-10-07

    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.

  6. RL-37, an alpha-helical antimicrobial peptide of the rhesus monkey.

    PubMed

    Zhao, C; Nguyen, T; Boo, L M; Hong, T; Espiritu, C; Orlov, D; Wang, W; Waring, A; Lehrer, R I

    2001-10-01

    Rhesus monkey bone marrow expresses a cathelicidin whose C-terminal domain comprises a 37-residue alpha-helical peptide (RL-37) that resembles human LL-37. Like its human counterpart, RL-37 rapidly permeabilized the membranes of Escherichia coli ML-35p and lysed liposomes that simulated bacterial membranes. When tested in media whose NaCl concentrations approximated those of extracellular fluids, RL-37 was considerably more active than LL-37 against staphylococci. Whereas human LL-37 contains five acidic residues and has a net charge of +6, rhesus RL-37 has only two acidic residues and a net charge of +8. Speculating that the multiple acidic residues of human LL-37 reduced its efficacy against staphylococci, we made a peptide (LL-37 pentamide) in which each aspartic acid of LL-37 was replaced by an asparagine and each glutamic acid was replaced by a glutamine. LL-37 pentamide's antistaphylococcal activity was substantially greater than that of LL-37. Thus, although the precursor of LL-37 is induced in human skin keratinocytes by injury or inflammation, its insufficiently cationic antimicrobial domain may contribute to the success of staphylococci in colonizing and infecting human skin. PMID:11557457

  7. 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

  8. Development of a flow feedback pulse duplicator system with rhesus monkey arterial input impedance characteristics.

    PubMed

    Schaub, J D; Koenig, S C; Schroeder, M J; Ewert, D L; Drew, G A; Swope, R D

    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. PMID:10445741

  9. Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys.

    PubMed

    Blevins, James E; Graham, James L; Morton, Gregory J; Bales, Karen L; Schwartz, Michael W; Baskin, Denis G; Havel, Peter J

    2015-03-01

    Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2× daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 ± 0.4% (≈0.6 kg; P < 0.05). Moreover, the low dose of OT suppressed 12-h chow intake by 26 ± 7% (P < 0.05). The higher dose of OT reduced 12-h chow intake by 27 ± 5% (P < 0.05) and 8-h fructose-sweetened beverage intake by 18 ± 8% (P < 0.05). OT increased EE during the dark cycle by 14 ± 3% (P < 0.05) and was associated with elevations of free fatty acids and glycerol and reductions in triglycerides suggesting increased lipolysis. Together, these data suggest that OT reduces BW in DIO rhesus monkeys through decreased food intake as well as increased EE and lipolysis.

  10. Induced neurocysticercosis in rhesus monkeys (Macaca mulatta) produces clinical signs and lesions similar to natural disease in man.

    PubMed

    Chowdhury, N; Saleque, A; Sood, N K; Singla, L D

    2014-01-01

    Neurocysticercosis is a serious endemic zoonosis resulting in increased cases of seizure and epilepsy in humans. The genesis of clinical manifestations of the disease through experimental animal models is poorly exploited. The monkeys may prove useful for the purpose due to their behavior and cognitive responses mimicking man. In this study, neurocysticercosis was induced in two rhesus monkeys each with 12,000 and 6,000 eggs, whereas three monkeys were given placebo. The monkeys given higher dose developed hyperexcitability, epileptic seizures, muscular tremors, digital cramps at 10 DPI, and finally paralysis of limbs, followed by death on 67 DPI, whereas the monkeys given lower dose showed delayed and milder clinical signs. On necropsy, all the infected monkeys showed numerous cysticerci in the brain. Histopathologically, heavily infected monkeys revealed liquefactive necrosis and formation of irregular cystic cavities lined by atrophied parenchymal septa with remnants of neuropil of the cerebrum. In contrast, the monkeys infected with lower dose showed formation of typical foreign body granulomas characterized by central liquefaction surrounded by chronic inflammatory response. It was concluded that the inflammatory and immune response exerted by the host against cysticerci, in turn, led to histopathological lesions and the resultant clinical signs thereof.

  11. Primacy and recency effects in rhesus monkeys (Macaca mulatta) using a serial probe recognition task. III. A developmental analysis.

    PubMed

    Matzke, S M; Castro, C A

    1998-04-01

    In children, the recency effect emerges prior to the primacy effect. To determine whether this dissociation is also seen in nonhuman primates, we evaluated the development of the primacy and recency effect in 3 young adult (35 months) and 4 adolescent (21 months) male rhesus monkeys (Macaca mulatta) using a six-item serial probe recognition (SPR) task. As predicted, the young adult monkeys displayed both effects, while the adolescent monkeys only displayed the recency effect. Not until after 26 months of training on the SPR task did the adolescent monkeys exhibit both the primacy and recency effect. Interference and strategy differences are discussed in terms of the results along with an interpretation of Rudy's (1992) configural association theory of cognitive development. Additional possible explanations for this developmental dissociation include the delayed maturation of the neocortical, hippocampal, and/or cholinergic systems, the latter two having been shown to be important in the expression of the primacy but not the recency effect.

  12. Intraday feeding patterns in infant rhesus monkeys and the effects of missing a meal.

    PubMed

    Riopelle, A J; Dietz, L S

    1989-01-01

    During the first month of life, infant rhesus monkeys (N = 96) were fed 7 times a day for the first 21 days and were fed 6 times a day thereafter. Fifty monkeys were fed SMA, a formula designed for human infants (9% protein, 43% carbohydrate, and 48% fat); 46 were fed one of three laboratory-confected diets varying in the amount of protein and carbohydrates provided. Although the diets had differential effects on weight gain, overall daily consumption was practically unaffected. A characteristic pattern was evident soon after birth: The first meal of the day (8:00 AM) was one of the largest, and the following two meals were usually the smallest; the next peak spanned the 4:00 PM and 8:00 PM feedings. The meal following a missed meal was slightly larger than normal. To some extent, the large meal at 8:00 AM can be attributed to the 10-hr absence of food during the night, but the peak at 4:00 PM and 8:00 PM cannot be so accounted for. The adult bicuspid pattern of eating hence appears to develop very early in life.

  13. 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

  14. Static lung mechanics of intact and excised rhesus monkey lungs and lobes.

    PubMed

    Pare, P D; Boucher, R; Michoud, M C; Hogg, J C

    1978-04-01

    Subdivisions of lung volume and pressure-volume (PV) curves of the lung and chest wall (CW) were measured in 12 rhesus monkeys (Macacca mulatta) under pentobarbital anesthesia. In addition, volumes and PV curves were obtained on the excised lungs and lobes of 12 cynomolgus monkeys (M. fasicularis). Boyle's law was used to determine functional residual capacity (FRC) in the intact animals and water displacement to determine minimal volume (MV) in the excised lungs. Total lung capacity (TLC = lung volume at a transpulmonary pressure of 30 cmH2O) was similar in vivo and in vitro (90 + 83 ml/kg) but residual volume (RV = volume at airway pressure of -50 cmH2O) and MV differed markedly (16.5 + 5.9 ml/kg). In the intact animals a very stiff CW appeared to determine RV, whereas airway closure determined MV in excised lungs. PV curves of upper and lower lobes were not different when expressed as %TLC but when expressed as milliliters of gas per gram of lung, the upper lobes contained significantly more gas per unit weight. PMID:417053

  15. Aspartame demand in rhesus monkeys: effects of volume and concentration manipulations.

    PubMed

    Wade-Galuska, Tammy; Galuska, Chad M; Winger, Gail; Woods, James H

    2007-01-10

    Three rhesus monkeys' lever presses produced aspartame-sweetened water according to a fixed-ratio schedule. The response requirement was increased across sessions and a demand-function analysis was used to assess the reinforcing effectiveness of different magnitudes of aspartame by manipulating reinforcer duration (1 and 3s) in Phase 1 and concentration (0.3, 0.5, 0.7, and 1.0mg/ml) in Phase 2. When duration was manipulated, the number of aspartame deliveries was mainly a function of the response requirement rather than unit price (responses/duration), suggesting that changes in duration did not significantly affect the reinforcing effectiveness of aspartame. When concentration was manipulated and the lowest concentration excluded, consumption was best described by unit price (responses/concentration) in two monkeys and by the response requirement in the third. Although results from the concentration manipulation provide some evidence that consumption was modulated by unit price, the results overall suggest that scalar equivalence does not exist between the components of unit price; specifically, the response requirement exerted a larger influence than duration or concentration on total consumption. Finally, a normalized demand analysis revealed that aspartame is a more elastic commodity than food and drug reinforcers.

  16. Age-Specific Gene Expression Profiles of Rhesus Monkey Ovaries Detected by Microarray Analysis

    PubMed Central

    Wei, Hengxi; Liu, Xiangjie; Yuan, Jihong; Li, Li; Zhang, Dongdong; Guo, Xinzheng; Liu, Lin; Zhang, Shouquan

    2015-01-01

    The biological function of human ovaries declines with age. To identify the potential molecular changes in ovarian aging, we performed genome-wide gene expression analysis by microarray of ovaries from young, middle-aged, and old rhesus monkeys. Microarray data was validated by quantitative real-time PCR. Results showed that a total of 503 (60 upregulated, 443 downregulated) and 84 (downregulated) genes were differentially expressed in old ovaries compared to young and middle-aged groups, respectively. No difference in gene expression was found between middle-aged and young groups. Differentially expressed genes were mainly enriched in cell and organelle, cellular and physiological process, binding, and catalytic activity. These genes were primarily associated with KEGG pathways of cell cycle, DNA replication and repair, oocyte meiosis and maturation, MAPK, TGF-beta, and p53 signaling pathway. Genes upregulated were involved in aging, defense response, oxidation reduction, and negative regulation of cellular process; genes downregulated have functions in reproduction, cell cycle, DNA and RNA process, macromolecular complex assembly, and positive regulation of macromolecule metabolic process. These findings show that monkey ovary undergoes substantial change in global transcription with age. Gene expression profiles are useful in understanding the mechanisms underlying ovarian aging and age-associated infertility in primates. PMID:26421297

  17. Estrogen formation and binding in the cerebral cortex of the developing rhesus monkey

    SciTech Connect

    MacLusky, N.J.; Naftolin, F.; Goldman-Rakic, P.S.

    1986-01-01

    These studies were undertaken to determine whether estrogen receptors and the microsomal enzyme system called the aromatase complex, which is responsible for conversion of androgen to estrogen, are present in the brain of the rhesus monkey during perinatal life. Four monkeys (three females-one fetus removed on day 153 of gestation and two infants, 5 and 6 days postnatal-and 1 male, 2 days postnatal) were studied. Cytosol estrogen receptors were detected in all brain regions examined. The apparent equilibrium dissociations constants for reaction of these sites with /sup 3/H/sup -/moxestrol were similar to those for uterine and pituitary cytosol estrogen receptors (0.3-1.1 nM). Within the brain, highest levels of binding were observed in the hypothalamus-preoptic area, with fairly even, lower concentrations throughout the cortical structures. Aromatase complex activity was detected in the majority of the tissue specimens. The highest levels of estrogen formation were observed in the hypothalamus. Among the cortical samples, the highest levels of aromatase complex activity were found in regions of the association cortex. The lowest levels of aromatase activity were found in the somatosensory and motor cortices of the postnatal animals. These results suggest that locally-formed estrogen may be involved in the effects of circulating androgens on the developing primate neocortex.

  18. Lack of behavioral effects in the rhesus monkey: High peak microwave pulses at 1. 3 GHz

    SciTech Connect

    D'Andrea, J.A.; Cobb, B.L.; de Lorge, J.O.

    1989-01-01

    The current safety standards for radiofrequency and microwave exposure do not limit the peak power of microwave pulses for general or occupational exposures. While some biological effects, primarily the auditory effect, depend on pulsed microwaves, hazards associated with very high peak-power microwave pulses in the absence of whole-body heating are unknown. Five rhesus monkeys, Macaca mulatta, were exposed to peak-power densitites of 131.8 W/sq cm (RMS) while performing a time-related behavioral task. The task was composed of a multiple schedule of reinforcement consisting of three distinct behavioral components: inter-response time, time discrimination, and fixed interval. Trained monkeys performed the multiple schedule during exposure to 1.3-GHz pulses at low pulse-repetition rates (2-32 Hz). No significant change was observed in any behavior during irradiation as compared to sham-irradiation sessions. Generalization of these findings to experimental results with higher peak-power densities, other pulse rates, different carrier frequencies, or other behaviors is limited.

  19. Lack of behavioral effects in the rhesus monkey: high peak microwave pulses at 1. 3 GHz

    SciTech Connect

    D'Andrea, J.A.; Cobb, B.L.; de Lorge, J.O.

    1989-01-01

    The current safety standards for radiofrequency and microwave exposure do not limit the peak power of microwave pulses for general or occupational exposures. While some biological effects, primarily the auditory effect, depend on pulsed microwaves, hazards associated with very high peak-power microwave pulses in the absence of whole-body heating are unknown. Five rhesus monkeys, Macaca mulatta, were exposed to peak-power densities of 131.8 W/cm2 (RMS) while performing a time-related behavioral task. The task was composed of a multiple schedule of reinforcement consisting of three distinct behavioral components: inter-response time, time discrimination, and fixed interval. Trained monkeys performed the multiple schedule during exposure to 1.3-GHz pulses at low pulse-repetition rates (2-32 Hz). No significant change was observed in any behavior during irradiation as compared to sham-irradiation sessions. Generalization of these findings to experimental results with higher peak-power densities, other pulse rates, different carrier frequencies, or other behaviors is limited.

  20. 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.

  1. Primary pulmonary sarcoma in a rhesus monkey after inhalation of plutonium dioxide

    SciTech Connect

    Hahn, F.F.; Brooks, A.L.; Mewhinney, J.A.

    1987-11-01

    A pulmonary fibrosarcoma of bronchial origin was discovered in a Rhesus monkey that died of pulmonary fibrosis 9 years after inhalation of plutonium-239 dioxide and with a radiation dose to lung of 1400 rad (14 Gy). It grew around the major bronchus of the right cardiac lung lobe and extended into the bronchial lumen and into surrounding pulmonary parenchyma. It also readily invaded muscular pulmonary arteries, resulting in infarction and scarring in the right cardiac lobe. Despite this aggressive growth, the tumor did not metastasize. The primary cause of death was severe pulmonary fibrosis involving the alveolar septa and and perivascular and peribronchial interstitium. Bullous or pericitrical emphysema was prominent. The initial lung burden of plutonium in this monkey was 270 nCi (10 kBq) which is equivalent to approximately 500 times the maximum permissible lung burden for man on a radioactivity per unit body weight basis. The time-dose relationship for survival is consistent with that of dogs and baboons that inhaled plutonium dioxide and died with lung tumors.

  2. The distribution of thyrotropin-releasing hormone (TRH) in the rhesus monkey spinal cord.

    PubMed

    Lechan, R M; Snapper, S B; Jacobson, S; Jackson, I M

    1984-01-01

    The distribution of thyrotropin-releasing hormone (TRH) in the Rhesus monkey spinal cord was studied using a highly specific antibody to TRH and the indirect peroxidase-antiperoxidase technique. TRH-positive fibers were found at all levels of the spinal cord and were in greatest concentration in the ventral gray, intermediolateral column and central gray. All motor nuclear groups in lamina IX of the ventral gray were innervated by TRH, frequently in close association with perikarya of alpha-motoneurons. The motor nuclei in the lumbar cord were the most heavily stained and contrasted to the minimal staining in the retrodorsolateral nuclear groups of the cervical, thoracic and sacral cord. Within the intermediolateral column, which contains the majority of preganglionic sympathetic neurons, TRH terminal fields reached their highest density between T2-T4 and T12-L2. Other preganglionic neurons including the nucleus intercalatus spinalis and the dorsal commissural nucleus were also densely innervated. These studies demonstrate the preferential distribution of TRH in the monkey spinal cord to regions containing alpha-motoneurons and preganglionic neurons and indicate that TRH may play an important role in the regulation of motor function and in the autonomic nervous system.

  3. 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.

  4. Similar stimulus features control visual classification in orangutans and rhesus monkeys.

    PubMed

    Diamond, Rachel F L; Stoinski, Tara S; Mickelberg, Jennifer L; Basile, Benjamin M; Gazes, Regina Paxton; Templer, Victoria L; Hampton, Robert R

    2016-01-01

    Many species classify images according to visual attributes. In pigeons, local features may disproportionately control classification, whereas in primates global features may exert greater control. In the absence of explicitly comparative studies, in which different species are tested with the same stimuli under similar conditions, it is not possible to determine how much of the variation in the control of classification is due to species differences and how much is due to differences in the stimuli, training, or testing conditions. We tested rhesus monkeys (Macaca mulatta) and orangutans (Pongo pygmaeus and Pongo abelii) in identical tests in which images were modified to determine which stimulus features controlled classification. Monkeys and orangutans were trained to classify full color images of birds, fish, flowers, and people; they were later given generalization tests in which images were novel, black and white, black and white line drawings, or scrambled. Classification in these primate species was controlled by multiple stimulus attributes, both global and local, and the species behaved similarly. PMID:26615515

  5. Epigenetic Mechanism Underlying the Development of Polycystic Ovary Syndrome (PCOS)-Like Phenotypes in Prenatally Androgenized Rhesus Monkeys

    PubMed Central

    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. PMID:22076147

  6. Mucinous gastric hyperplasia in a colony of rhesus monkeys (Macaca mulatta) induced by polychlorinated biphenyl (Aroclor 1254)

    SciTech Connect

    Geistfeld, J.G.; Bond, M.G.; Bullock, B.C.; Varian, M.C.

    1982-02-01

    Since 1971, 45 of 259 male rhesus monkeys housed in a primate building have died of a chronic and progressive disease characterized by diarrhea, dehydration, weakness, gingivitis, emaciation, and alopecia. The principal necropsy finding in these monkeys, and in eight others killed for experimental purposes, was hypertrophic and hyperplastic mucinous gastropathy involving both the mucosa and submucosa. The toxic agent involved was identified as the polychlorinated biphenyl (PCB), Aroclor 1254. The suspected source of the toxic agent was a concrete sealer used during building construction.

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

    PubMed Central

    Czoty, Paul W.

    2015-01-01

    Background 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). Methods Monkeys self-administered cocaine (0.0–1.0 mg/kg/injection, i.v.) under a 300-second 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: one hour, 5 days/week with daily intake equaling 2.0 g/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 (0.0–1.0 g/kg. i.v.) prior to cocaine self-administration sessions (n=4). Results In 5 of 6 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 2 of 3 monkeys. Acute EtOH infusions only decreased self-administration of lower cocaine doses. Conclusions 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. PMID:26048636

  8. The behavioral neurobiology of self-injurious behavior in rhesus monkeys.

    PubMed

    Kraemer, G W; Clarke, A S

    1990-01-01

    1. Self-injurious behavior (SIB) is prevalent among institutionalized children, but the efficacy of current behavioral and pharmacological treatments is marginal. 2. There is evidence that SIB in humans has a neurobiological basis. A better understanding of the neurobiological factors that may promote or cause SIB is necessary for the development of effective pharmacologic treatments. 3. SIB that is similar in some respects to SIB in humans occurs in nonhuman primates that have been deprived of social experience early in life. An analysis of the "cause" of SIB suggests that it is a relatively straight-forward example of the development of neurobiological and behavioral aspects of aggressive behavior in the absence of social factors that would normally bring the behavior under environmental control. Once induced, however, it becomes environmentally autonomous and its proximal cause is neurobiological in nature. 4. There are three lines of evidence that nonhuman primate SIB is linked to malfunctions in the norepinephrine (NE) and serotonin (5HT) neurotransmitter systems. The activity of these systems appears to be altered by psychosocial deprivation. The functional relationship between the two systems appears to be altered or absent in socially deprived monkeys. Pharmacologic agents that act on these systems alter SIB in monkeys. 5. Preliminary data from socially deprived rhesus monkeys are consistent in major respects with studies linking altered serotonin systems to self-injurious behavior and suicidal motivation in humans who also probably suffer from social deprivation. 6. Taken together, these findings indicate that developmental study of biogenic amine systems, particularly finding ways to circumvent deficits in, or restore functional linkages between, the 5HT and NE systems, will lead to a greater understanding of the neurobiologic basis of SIB in humans and animals and will enable us to develop more effective treatments of SIB.

  9. Self-administration of cocaine-pentobarbital mixtures by rhesus monkeys.

    PubMed

    Woolverton, W L; Wang, Zhixia

    2009-03-01

    A number of experiments have evaluated self-administration of the combination of a stimulant and an opioid. Less is known about the combination of a stimulant and a CNS depressant. The present experiment was designed to examine self-administration of the mixture of cocaine and pentobarbital (PB). Rhesus monkeys (n=4) prepared with i.v. catheters were allowed to self-administer cocaine or saline under a progressive-ratio schedule. When responding was stable, doses of cocaine and PB, alone or in combination, were made available in test sessions. Cocaine functioned as a positive reinforcer in a dose-related manner in all monkeys. PB functioned as a relatively weaker reinforcer in one of four monkeys. Self-administration of intermediate doses of cocaine (0.025-0.1mg/kg per injection) was decreased when mixed with PB (0.05-0.2mg/kg per injection); full maximum responding was re-established when cocaine dose was increased. The magnitude of the shift to the right in the cocaine dose-response function was directly related to PB dose. When PB was given as an i.v. pretreatment there was no effect on cocaine self-administration up to a sedative dose of PB (5.6 mg/kg), suggesting that responding was not non-specifically suppressed by PB. Thus, simultaneous self-administration of PB diminished the potency but not the strength of cocaine as a reinforcer, potentially encouraging self-administration of larger doses of cocaine. PMID:19054630

  10. Neurobehavioral deficits in neonatal rhesus monkeys exposed to cocaine in utero.

    PubMed

    He, Na; Bai, Jie; Champoux, Maribeth; Suomi, Stephen J; Lidow, Michael S

    2004-01-01

    In spite of significant efforts, the neurobehavioral deficits in infants born from cocaine-abusing mothers have not been clearly defined. In the present study, we examined the presence of these abnormalities in a rhesus monkey model of prenatal cocaine exposure using a nonhuman primate adaptation of the Neonatal Behavioral Assessment Scale (NBAS). Pregnant monkeys (n = 14) received 10 mg/kg cocaine twice a day orally (in fruit treats) from the 40th through 102nd postconception days (PCD40-PCD102), which is the period of cerebral cortical neuronogenesis (approximately second trimester). The control consisted of pregnant monkeys (n = 14) receiving fruit treats only. The animals were allowed to deliver vaginally at term (approximately PCD165). The first testing session was conducted on PCD171 (within the first week after birth); the second testing session was conducted on PCD177 (within the second week after birth); the third test was conducted on PCD183 (within the third week after birth); and the fourth testing session was conducted on PCD189 (within the fourth week after birth). The prenatally cocaine-exposed infants showed deficits in orientation, state control, and motor maturity, which were detectable during the second, third, and fourth testing sessions. The same testing sessions also revealed a significant reduction in the time devoted to toy manipulation, which points to impaired attention. None of these abnormalities were seen during the first testing session. The first session, however, revealed increased tremulousness (one of the indicators of autonomic stability) in the prenatally cocaine-exposed infants. This impairment disappeared by the third testing session. The present findings demonstrate the potential of prenatal cocaine exposure to induce neurobehavioral deficits detectable by NBAS-like testing in primate infants. PMID:15001210

  11. Pharmacologic characterization of a nicotine-discriminative stimulus in rhesus monkeys.

    PubMed

    Cunningham, Colin S; Javors, Martin A; McMahon, Lance R

    2012-06-01

    This study examined mechanisms by which nicotine (1.78 mg/kg base s.c.) produces discriminative stimulus effects in rhesus monkeys. In addition to nicotine, various test compounds were studied including other nicotinic acetylcholine receptor agonists (varenicline and cytisine), antagonists [mecamylamine and the α4β2 receptor-selective antagonist dihydro-β-erythroidine (DHβE)], a nicotinic acetylcholine receptor antagonist/indirect-acting catecholamine agonist (bupropion), and non-nicotinics (cocaine and midazolam). Nicotine, varenicline, and cytisine dose-dependently increased drug-lever responding; the ED(50) values were 0.47, 0.53, and 39 mg/kg, respectively. Bupropion and cocaine produced 100% nicotine-lever responding in a subset of monkeys, whereas mecamylamine, DHβE, and midazolam produced predominantly vehicle-lever responding. The training dose of nicotine resulted in 1128 ng/ml cotinine in saliva. Mecamylamine antagonized the discriminative stimulus effects of nicotine and varenicline, whereas DHβE was much less effective. Nicotine and varenicline had synergistic discriminative stimulus effects. In monkeys responding predominantly on the vehicle lever after a test compound (bupropion, cocaine, and midazolam), that test compound blocked the nicotine-discriminative stimulus, perhaps reflecting a perceptual-masking phenomenon. These results show that nicotine, varenicline, and cytisine produce discriminative stimulus effects through mecamylamine-sensitive receptors (i.e., nicotinic acetylcholine) in primates, whereas the involvement of DHβE-sensitive receptors (i.e., α4β2) is unclear. The current nicotine-discrimination assay did not detect a difference in agonist efficacy between nicotine, varenicline, and cytisine, but did show evidence of involvement of dopamine. The control that nicotine has over choice behavior can be disrupted by non-nicotinic compounds, suggesting that non-nicotinics could be exploited to decrease the control that tobacco has

  12. 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.

  13. Elimination of type D retrovirus infection from group-housed rhesus monkeys using serial testing and removal.

    PubMed

    Lerche, N W; Marx, P A; Gardner, M B

    1991-04-01

    Type D retrovirus was successfully eliminated from an infected population of group-housed rhesus monkeys by serial testing of all animals for virus and antibody and subsequent removal of positives. This population of 53 rhesus had been housed together for 1 year prior to the initiation of the test and removal program, with six deaths from type D retrovirus-induced immunodeficiency disease occurring during this period. No new infections were detected after four rounds of testing. Of the 47 animals present at the start of the testing program, 17 (35%) remained after the elimination of type D virus from this group. These animals and their offspring have remained healthy and antibody negative for more than 2 years. These results demonstrate that elimination of type D retroviruses from rhesus macaque colonies is feasible, and that the objective of establishing and maintaining retrovirus-free colonies is realistic and achievable.

  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.

  15. Characterization of perfect microsatellite based on genome-wide and chromosome level in Rhesus monkey (Macaca mulatta).

    PubMed

    Xu, Yongtao; Hu, Zongxiu; Wang, Chen; Zhang, Xiuyue; Li, Jing; Yue, Bisong

    2016-11-01

    Microsatellite studies based on chromosomes level would contribute to the biometric correlation analysis of chromosome and microsatellite applications on the specific chromosome. In this study, the total microsatellite length of 1,141,024 loci was 21.8Mb, which covered about 0.74% of the male Rhesus monkey genome. Perfect mononucleotide SSRs were the most abundant, followed by the pattern: perfect di->tetra->tri->penta->hexanucleotide SSRs. The main range of repeat times focused on 12-32 times (mono-), 7-23 times (di-), 5-10 times (tri-), 4-14 times (tetra-), 4-9 times (penta-), 4-8 times (hexa-), respectively. The largest SSRs number was found in chromosome 1 with 94,347 loci, followed by chromosome 3, 2, 7 and 5, and the smallest number was in chromosome 18. The predominant repeat types in male Rhesus monkey genome and chromosome Y were basically A, AC, AG, AAT, AAC, AAAT, AAAC, AAAG, AAACA and AAACAA. SSRs number of all chromosomes was closely positively correlated with chromosome sequence size (r=0.969, p<0.01), and significantly negatively correlated with abundance (r=-0.24, 0.01Rhesus monkey, which might contributed to the DNA methylation of CpG islands for sex chromosome X inactivation and expression regulation. These results and exported tetranucleotide repeat sequences in each chromosome for primer design would facilitate the exploration of microsatellites structural function, composition mode and molecular markers development in Rhesus monkey genome. PMID:27395431

  16. 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.

  17. Dose-response studies on the spermatogonial stem cells of the rhesus monkey (Macaca mulatta) after X irradiation

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; Davids, J.A.; Warmer, C.J.; Bootsma, A.L.; de Rooij, D.G. )

    1989-09-01

    Studies of the dose response of the spermatogonial stem cells in the rhesus monkey were performed at intervals of 130 and 160 days after graded doses of X irradiation. The D0 of the spermatogonial stem cells was established using the total numbers of the type A spermatogonia that were present at 130 and 160 days after irradiation and was found to be 1.07 Gy; the 95% confidence interval was 0.90-1.34 Gy.

  18. Characterization of perfect microsatellite based on genome-wide and chromosome level in Rhesus monkey (Macaca mulatta).

    PubMed

    Xu, Yongtao; Hu, Zongxiu; Wang, Chen; Zhang, Xiuyue; Li, Jing; Yue, Bisong

    2016-11-01

    Microsatellite studies based on chromosomes level would contribute to the biometric correlation analysis of chromosome and microsatellite applications on the specific chromosome. In this study, the total microsatellite length of 1,141,024 loci was 21.8Mb, which covered about 0.74% of the male Rhesus monkey genome. Perfect mononucleotide SSRs were the most abundant, followed by the pattern: perfect di->tetra->tri->penta->hexanucleotide SSRs. The main range of repeat times focused on 12-32 times (mono-), 7-23 times (di-), 5-10 times (tri-), 4-14 times (tetra-), 4-9 times (penta-), 4-8 times (hexa-), respectively. The largest SSRs number was found in chromosome 1 with 94,347 loci, followed by chromosome 3, 2, 7 and 5, and the smallest number was in chromosome 18. The predominant repeat types in male Rhesus monkey genome and chromosome Y were basically A, AC, AG, AAT, AAC, AAAT, AAAC, AAAG, AAACA and AAACAA. SSRs number of all chromosomes was closely positively correlated with chromosome sequence size (r=0.969, p<0.01), and significantly negatively correlated with abundance (r=-0.24, 0.01Rhesus monkey, which might contributed to the DNA methylation of CpG islands for sex chromosome X inactivation and expression regulation. These results and exported tetranucleotide repeat sequences in each chromosome for primer design would facilitate the exploration of microsatellites structural function, composition mode and molecular markers development in Rhesus monkey genome.

  19. Type 2 diabetes mellitus non-genetic Rhesus monkey model induced by high fat and high sucrose diet.

    PubMed

    Lu, Shuai-yao; Qi, Su-dong; Zhao, Yuan; Li, Yan-yan; Yang, Feng-mei; Yu, Wen-hai; Jin, Ma; Chen, Li-Xiong; Wang, Jun-bin; He, Zhan-long; Li, Hong-jun

    2015-01-01

    To build an ideal animal model for studying the mechanism of occurrence, developing and treating of diabetes become a more important issue, facing with the fact that the big threat of diabetes to human health has been worsen. First, we used the normal control diets or the high-fat/high-sucrose diets to feed the adult rhesus monkeys and the macaques induced by the high-fat/high-sucrose diets in the high-fat/high-sucrose group and the type 2 diabetes mellitus (T2DM) group developed the hyperglycemia, hyperinsulinemia at 6 months in accordance with the precious researches that reported that minipigs, rats and mice could develop hyperglycemia, hyperinsulinemia, hyperlipidemia and obesity after being induced with high-fat/high-carbohydrate diets. Second, the rhesus monkeys in T2DM group were injected STZ at a low dosage of 35 mg/kg BW to induce glucose persistent elevation which maintained pretty well after 12 months. Third, we took the assay of glucose tolerance test and insulin resistance index, assessed the changing tendency of serum resistin and analysed the pathological characteristics of the tissues like pancreas and liver by staining in different ways. The results indicate the rhesus monkeys in T2DM group have lots of clinical features of T2DM. The experimental non-genetic T2DM rhesus monkeys model not only contribute to simulating of clinical manifestations and pathological features of human T2DM, but also may be a good kind of model for research on the treatment of T2DM and for new drugs evaluation.

  20. Looking Ahead? Computerized Maze Task Performance by Chimpanzees (Pan troglodytes), Rhesus Monkeys (Macaca mulatta), Capuchin Monkeys (Cebus apella), and Human Children (Homo sapiens)

    PubMed Central

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

    2015-01-01

    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. PMID:25798793

  1. 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. PMID:25798793

  2. 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.

  3. Extraocular Muscle Motor Units Characterized By Spike-Triggered Averaging In Alert Monkey

    PubMed Central

    Gamlin, Paul D.; Miller, Joel M.

    2011-01-01

    Single-unit recording in macaque monkeys has been widely used to study extraocular motoneuron behavior during eye movements. However, primate extraocular motor units have only been studied using electrical stimulation in anesthetized animals. To study motor units in alert, behaving macaques, we combined chronic muscle force transducer (MFT) and single-unit extracellular motoneuron recordings. During steady fixation with low motoneuron firing rates, we used motoneuron spike-triggered averaging of MFT signals (STA-MFT) to extract individual motor unit twitches, thereby characterizing each motor unit in terms of twitch force and dynamics. It is then possible, as in conventional studies, to determine motoneuron activity during eye movements, but now with knowledge of underlying motor unit characteristics. We demonstrate the STA-MFT technique for medial rectus motor units. Recordings from 33 medial rectus motoneurons in three animals identified 20 motor units, which had peak twitch tensions of 0.5 – 5.25 mg, initial twitch delays averaging 2.4ms, and time to peak contraction averaging 9.3ms. These twitch tensions are consistent with those reported in unanesthetized rabbits, and with estimates of the total number of medial rectus motoneurons and twitch tension generated by whole-nerve stimulation in monkey, but are substantially lower than those reported for lateral rectus motor units in anesthetized squirrel monkey. Motor units were recruited in order of twitch tension magnitude with stronger motor units reaching threshold further in the muscle’s ON-direction, showing that, as in other skeletal muscles, medial rectus motor units are recruited according to the “size principle”. PMID:22108141

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

    SciTech Connect

    Woodard, C.L.; Calamaio, C.A.; Kaminskis, A.; Anderson, D.R.; Harris, L.W.

    1993-05-13

    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) 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.

  5. Recent developments in vaccination against malaria: Immunization of rhesus monkeys with blood-stage antigens of Plasmodium knowlesi*

    PubMed Central

    Rieckmann, K. H.; Cabrera, E. J.; Campbell, G. H.; Jost, R. C.; Miranda, R.; O'Leary, T. R.

    1979-01-01

    Evaluation of the efficacy of 3 nonviable blood-stage antigens—schizont Ag, merozoite Ag, and ”French press” Ag—of Plasmodium knowlesi, emulsified in Freund's complete adjuvant (FCA), was carried out in a study involving 32 rhesus monkeys. After 2 immunizations, administered 6 weeks apart, monkeys were challenged with a variant of P. knowlesi different from that used for immunization. All 8 control monkeys that received either PBS or FCA developed a severe parasitaemia and died of the infection within 12 days after parasite challenge. In the group that received the freeze-thawed schizont Ag, 5 of the 8 monkeys died at the same time as the controls, 1 died a day later, and 2 survived the infection (maximum parasitaemia: 0.7%; 3.2%). In the freeze-thawed merozoite Ag group, 1 monkey died at the same time as the controls, 5 monkeys died between 14 and 17 days after challenge, and 2 monkeys survived the infection (maximum parasitaemia: <0.01%; 2.7%). In the lyophilized French press Ag group, 2 monkeys died at the same time as the controls, 2 died between 12 and 15 days after challenge, and 4 survived the infection (maximum parasitaemia: 1.2%; 0.4%; 0.9%; 0.07%). Immunized monkeys failed to gain weight during the period of immunization and abscess formation at injection sites was comparable in monkeys of the 3 Ag groups. Reticulocytosis and anaemia developed in all monkeys that survived longer than 12 days after challenge, even in monkeys with very low-grade levels of parasitaemia. Various tests were performed to assess humoral or cell-mediated immune responses during the period of immunization and after challenge. No clear-cut relationship could be established between the results of any of these tests and the survival of immunized monkeys after parasite challenge. Some of the results, however, suggest that there might be some relationship between cell-mediated responses and the survival of immunized monkeys beyond the survival time of control monkeys. PMID

  6. Effects of inhalation exposures to an M1-receptor agonist on ventilation in rhesus monkeys.

    PubMed

    Allen, D L; Leiter, P A; Tielking, R L; Hoffman, W P; Vidyashankar, A N; van Lier, R B; Wolff, R K

    1999-11-01

    Information was needed on effects of possible occupational inhalation exposure to an M1-receptor agonist (xanomeline) such as might occur during the manufacturing process. Both acute and repeated inhalation exposures to xanomeline were carried out in six male rhesus monkeys using a head-dome exposure system. Exposure concentrations ranged from 0.3 to 10 mg/m3. The exposure durations were up to 2 weeks. Decreases in tidal volume and increases in respiratory frequency were both time and concentration related during acute exposures. These effects were blocked with atropine pre-treatment. Correlation with pulmonary resistance measurements in two monkeys suggested that these were bronchoconstrictive changes that increased with severity with time at a given concentration and with concentration when measured after a constant exposure time. The dose-response was relatively steep with 10 mg/m3 becoming intolerable to the monkeys after approximately 15 minutes, but no measurable effects were observed at 0.3 mg/m3 after up to 4 hours of exposure. To investigate the effects of repeated exposures, monkeys were exposed for 4 hr/day, 5 days/wk for 2 weeks to 0.0 (air only), 0.3, and 1.2 mg xanomeline/m3 of air. When compared to the air-only exposure, 0.3 mg/m3 caused no significant changes in tidal volume. In contrast, 1.2 mg/m3 caused a rapid and significant decrease in tidal volume that was sustained throughout the 4-hr exposure. A slower rise in breathing frequency also occurred. Repeated exposures did not alter the effects seen after a single exposure. It is concluded that xanomeline, a M1-receptor agonist, can acutely alter normal ventilation in non-human primates at airborne concentrations > or = 0.6 mg/m3 and should be carefully controlled in a manufacturing environment. The no-observed-effect concentration was 0.3 mg/m3.

  7. The effect of ketoprofen creams on periodontal disease in rhesus monkeys.

    PubMed

    Li, K L; Vogel, R; Jeffcoat, M K; Alfano, M C; Smith, M A; Collins, J G; Offenbacher, S

    1996-11-01

    Ketoprofen creams were evaluated for the treatment of periodontal disease in a placebo-controlled, double-blind study in the rhesus monkeys, Macaca mulatta. Two formulations containing ketoprofen (1%), with or without vitamin E, were evaluated against appropriate controls (8 monkeys per group). Two weeks prior to treatment, the animals received prophylaxis on only the left side of the mouth (spontaneous model). Selected teeth on the right side of the mouth were ligated (ligature model). The creams were administered to the gingiva once daily at a standard dose of 1.8 ml per monkey for 6 months. Clinical assessments were made 2 wk before initiation, at baseline and 1, 2, 3 and 6 months post-treatment. The clinical parameters included plaque formation, gingival redness, edema, bleeding on probing and Ramfjord Attachment Level measurements (RAL). Radiographs were taken at 2 wk before initiation, baseline and at 3 and 6 months post-treatment. Digital, subtraction radiography was used to measure vertical linear bone loss along the interproximal root surfaces of the left and right mandibular first molars. Gingival crevicular fluid (GCF) was collected for biochemical assays on PGE2, TxB2, LTB4, IL-1 beta and TNF alpha. There were no significant differences among groups with respect to gingival indices. Radiographic data demonstrated significant positive effects on bone activity in both groups treated with ketoprofen formulations with improvement over time in the ligature model (0.01 < or = p < or = 0.04). The placebo group exhibited bone loss of 1.96 +/- 0.48 and 1.40 +/- 0.56 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream showed an apparent bone gain of 0.28 +/- 0.41 and 0.78 +/- 0.47 mm per site at 3 and 6 months, respectively. The group treated with ketoprofen cream containing vitamin E showed a mean bone loss of 0.41-0.48 mm per site at 3 months with improvement to an apparent bone gain of 0.31 +/- 0.44 mm per site at 6 months. The

  8. Changes in yearling rhesus monkeys' relationships with their mothers after sibling birth.

    PubMed

    Devinney, B J; Berman, C M; Rasmussen, K L

    2001-08-01

    The birth of a new sibling is believed to signify an abrupt and important transition in a young primate's relationship with its mother-one that is of potential importance from at least three theoretical perspectives: attachment theory, parent-offspring conflict theory, and dynamic assessment models. This study examines changes in relationships between free-ranging yearling rhesus monkeys (Macaca mulatta) and their mothers concomitant with the birth of the mother's next infant, and tests predictions derived from each theoretical perspective. We observed 31 yearling rhesus on Cayo Santiago, Puerto Rico, 3 months before and 3 months after their siblings' births, using focal animal sampling methods. Changes in measures related to mother-yearling interaction and yearling distress were examined using repeated-measures analysis of variance. After sibling birth, mothers and yearlings abruptly reduced amounts of time in contact and increased amounts of time at a distance and out of sight of one another. Mothers and yearlings played approximately equal roles in bringing about decreases in proximity, and yearlings took the primary roles in bringing about decreases in contact. Rates of maternal aggression toward yearlings increased immediately and markedly after birth, possibly providing yearlings with early cues regarding subsequent decreased levels of maternal care. There were no marked increases in overt signs of yearling distress (e.g., vocalizations or tantrums) following the births. We conclude that yearlings generally acquiesced to reduced levels of care, responding behaviorally with increased independence and maturity. In this sense, our study provides preliminary support for dynamic assessment models over attachment theory and parent-offspring conflict theory models. PMID:11468750

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

    SciTech Connect

    Zhu, Hai-Ying; Kang, Jin-Dan; Li, Suo; Jin, Jun-Xue; Hong, Yu; Jin, Long; Guo, Qing; Gao, Qing-Shan; Yan, Chang-Guo; Yin, Xi-Jun

    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 rhesus 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.

  10. Emergence and evolution of inter-specific segregating retrocopies in cynomolgus monkey (Macaca fascicularis) and rhesus macaque (Macaca mulatta)

    PubMed Central

    Zhang, Xu; Zhang, Qu; Su, Bing

    2016-01-01

    Retroposition is an RNA-mediated mechanism to generate gene duplication, and is believed to play an important role in genome evolution and phenotypic adaptation in various species including primates. Previous studies suggested an elevated rate of recent retroposition in the rhesus macaque genome. To better understand the impact of retroposition on macaque species which have undergone an adaptive radiation approximately 3–6 million years ago, we developed a bioinformatics pipeline to identify recently derived retrocopies in cynomolgus monkeys. As a result, we identified seven experimentally validated young retrocopies, all of which are polymorphic in cynomolgus monkeys. Unexpectedly, five of them are also present in rhesus monkeys and are still segregating. Molecular evolutionary analysis indicates that the observed inter-specific polymorphism is attribute to ancestral polymorphism. Further population genetics analysis provided strong evidence of balancing selection on at least one case (Crab-eating monkey retrocopy 6, or CER6) in both species. CER6 is in adjacent with an immunoglobulin related gene and may be involved in host-pathogen interaction, a well-known target of balancing selection. Altogether, our data support that retroposition is an important force to shape genome evolution and species adaptation. PMID:27600022

  11. Emergence and evolution of inter-specific segregating retrocopies in cynomolgus monkey (Macaca fascicularis) and rhesus macaque (Macaca mulatta).

    PubMed

    Zhang, Xu; Zhang, Qu; Su, Bing

    2016-09-07

    Retroposition is an RNA-mediated mechanism to generate gene duplication, and is believed to play an important role in genome evolution and phenotypic adaptation in various species including primates. Previous studies suggested an elevated rate of recent retroposition in the rhesus macaque genome. To better understand the impact of retroposition on macaque species which have undergone an adaptive radiation approximately 3-6 million years ago, we developed a bioinformatics pipeline to identify recently derived retrocopies in cynomolgus monkeys. As a result, we identified seven experimentally validated young retrocopies, all of which are polymorphic in cynomolgus monkeys. Unexpectedly, five of them are also present in rhesus monkeys and are still segregating. Molecular evolutionary analysis indicates that the observed inter-specific polymorphism is attribute to ancestral polymorphism. Further population genetics analysis provided strong evidence of balancing selection on at least one case (Crab-eating monkey retrocopy 6, or CER6) in both species. CER6 is in adjacent with an immunoglobulin related gene and may be involved in host-pathogen interaction, a well-known target of balancing selection. Altogether, our data support that retroposition is an important force to shape genome evolution and species adaptation.

  12. Emergence and evolution of inter-specific segregating retrocopies in cynomolgus monkey (Macaca fascicularis) and rhesus macaque (Macaca mulatta).

    PubMed

    Zhang, Xu; Zhang, Qu; Su, Bing

    2016-01-01

    Retroposition is an RNA-mediated mechanism to generate gene duplication, and is believed to play an important role in genome evolution and phenotypic adaptation in various species including primates. Previous studies suggested an elevated rate of recent retroposition in the rhesus macaque genome. To better understand the impact of retroposition on macaque species which have undergone an adaptive radiation approximately 3-6 million years ago, we developed a bioinformatics pipeline to identify recently derived retrocopies in cynomolgus monkeys. As a result, we identified seven experimentally validated young retrocopies, all of which are polymorphic in cynomolgus monkeys. Unexpectedly, five of them are also present in rhesus monkeys and are still segregating. Molecular evolutionary analysis indicates that the observed inter-specific polymorphism is attribute to ancestral polymorphism. Further population genetics analysis provided strong evidence of balancing selection on at least one case (Crab-eating monkey retrocopy 6, or CER6) in both species. CER6 is in adjacent with an immunoglobulin related gene and may be involved in host-pathogen interaction, a well-known target of balancing selection. Altogether, our data support that retroposition is an important force to shape genome evolution and species adaptation. PMID:27600022

  13. Intestinal manifestations of experimental SIV-infection in rhesus monkeys (Macaca mulatta): a histological and ultrastructural study.

    PubMed

    Kuhn, E M; Mätz-Rensing, K; Stahl-Hennig, C; Makoschey, B; Hunsmann, G; Kaup, F J

    1997-10-01

    Intestinal lesions were studied in 32 rhesus monkeys experimentally infected with different strains of simian immunodeficiency virus SIVmac (251/32H, 251/32H-SPL and 251/MPBL) by light microscopy, transmission and scanning electron microscopy. A spectrum of primary and secondary manifestations of SIV-infection were detected. Primary changes included 'SIV-enteropathy' in 12 monkeys and virus-induced syncytial giant cell formation (GCF) of the intestine in two animals. A primary virus-induced enteropathy occurred both as only histologically visible 'SIV-enteropathy' and as 'AIDS-enteropathy' accompanied by clinical signs of enteritis. Secondary opportunistic infections (Balantidium coli, Cryptosporidium, Trichuris, Trichomonas, Spironucleus, Mycobacteria and Cytomegalovirus) were identified in 27 animals and three monkeys developed malignant lymphomas involving the intestinal tract. Compared to intestinal lesions in HIV-infected patients, differences were found concerning the incidence of GCF and the range of opportunistic infections, with cryptosporidium, cytomegalovirus and mycobacteria occurring in both SIV-infected macaques and AIDS patients. The present observations revealed that SIV-infected rhesus monkeys provide an excellent model both for studies on the pathogenesis of HIV-enteropathy and opportunistic infections and for the development of therapies against cryptosporidial, cytomegalovirus and mycobacteria infection. Comparison of three SIV-strains revealed differences in primary and secondary lesions observed: SIVmac251/MPBL was correlated with severe primary SIV-induced pathologic changes and SIVmac251-SPL-infected animals showed a higher incidence of malignant lymphomas. PMID:9394615

  14. Sexual maturation in male rhesus monkeys: importance of neonatal testosterone exposure and social rank.

    PubMed

    Mann, D R; Akinbami, M A; Gould, K G; Paul, K; Wallen, K

    1998-03-01

    In a 5-year longitudinal study, we examined the effect of disrupting the neonatal activity of the pituitary-testicular axis on the sexual development of male rhesus monkeys. Animals in a social group under natural lighting conditions were treated with a GnRH antagonist (antide), antide and androgen, or both vehicles, from birth until 4 months of age. In antide-treated neonates, serum LH and testosterone were near or below the limits of detection throughout the neonatal period. Antide + androgen-treated neonates had subnormal serum LH, but above normal testosterone concentrations during the treatment period. From 6 to 36 months of age, serum LH and testosterone were near or below the limits of detection. Ten of 12 control animals reached puberty during the breeding season of their 4th year, compared with five of 10 antide- and three of eight antide + androgen-treated animals. Although matriline rank was balanced across treatment groups at birth, a disruption within the social group during year 2 resulted in a marginally lower social ranking of the two treated groups compared with the controls. More high (78%) than low (22%) ranking animals reached puberty during year 4. During the breeding season of that year, serum LH, testosterone and testicular volume were positively correlated with social rank. Thus the lower social rank of treated animals may have contributed to the subnormal numbers of these animals reaching puberty during year 4. However, of those animals achieving puberty during year 4, the pattern of peripubertal changes in serum testosterone and testicular volume differed between control and antide-treated animals. The results appear to suggest that the disruption of normal activity of the neonatal pituitary--testicular axis retarded sexual development, but that social rank is a key regulatory factor in setting the timing of sexual maturation in male rhesus monkeys. The effect of neonatal treatment with antide and low social rank on sexual development

  15. Olanzapine-induced suppression of cocaine self-administration in rhesus monkeys.

    PubMed

    Howell, Leonard L; Wilcox, Kristin M; Lindsey, Kimberly P; Kimmel, Heather L

    2006-03-01

    The neuropharmacological profile of the atypical antipsychotic, olanzapine, is consistent with a potentially useful medication for cocaine abuse. The present study utilized an i.v. drug self-administration paradigm in nonhuman primates to obtain definitive evidence regarding the effectiveness of olanzapine to modulate the reinforcing effects of cocaine. The effects of olanzapine were compared directly to those of the neuroleptic, haloperidol. Rhesus monkeys (n=7) were trained to self-administer cocaine (0.03-0.3 mg/kg/injection) under a second-order, fixed-interval 600-s schedule with fixed ratio 20 components. Experimental sessions comprised five consecutive fixed intervals, each followed by a 1-min timeout. In drug-interaction experiments, a single dose of olanzapine (0.03-0.3 mg/kg) or haloperidol (0.01-0.03 mg/kg) was administered i.v. 15 min presession for at least three consecutive sessions. In drug-substitution experiments, different doses of olanzapine (0.01-0.1 mg/kg/injection) were substituted for cocaine until responding stabilized. Olanzapine caused dose-related decreases in cocaine self-administration at pretreatment doses that had no overt behavioral effects indicative of sedation. A dose of 0.1 mg/kg eliminated cocaine self-administration in all subjects. In contrast, doses of haloperidol that suppressed cocaine self-administration induced marked sedation and catalepsy. Olanzapine failed to maintain self-administration behavior above saline extinction levels over a range of unit doses. In vivo microdialysis experiments in a second group of awake rhesus monkeys (n=3) confirmed previous reports in rodents that olanzapine effectively increases extracellular dopamine in ventral striatum. The dose of olanzapine that markedly suppressed cocaine self-administration behavior increased dopamine to approximately 190% of control values. Lastly, pretreatment with fluoxetine had no systematic effect on olanzapine-induced increases in striatal dopamine. The

  16. Neural basis for eye velocity generation in the vestibular nuclei of alert monkeys during off-vertical axis rotation

    NASA Technical Reports Server (NTRS)

    Reisine, H.; Raphan, T.; Cohen, B. (Principal Investigator)

    1992-01-01

    Activity of "vestibular only" (VO) and "vestibular plus saccade" (VPS) units was recorded in the rostral part of the medial vestibular nucleus and caudal part of the superior vestibular nucleus of alert rhesus monkeys. By estimating the "null axes" of recorded units (n = 79), the optimal plane of activation was approximately the mean plane of reciprocal semicircular canals, i.e., lateral canals, left anterior-right posterior (LARP) canals or right anterior-left posterior (RALP) canals. All units were excited by rotation in a direction that excited a corresponding ipsilateral semicircular canal. Thus, they all displayed a "type I" response. With the animal upright, there were rapid changes in firing rates of both VO and VPS units in response to steps of angular velocity about a vertical axis. The units were bidirectionally activated during vestibular nystagmus (VN), horizontal optokinetic nystagmus (OKN), optokinetic after-nystagmus (OKAN) and off-vertical axis rotation (OVAR). The rising and falling time constants of the responses to rotation indicated that they were closely linked to velocity storage. There were differences between VPS and VO neurons in that activity of VO units followed the expected time course in response to a stimulus even during periods of drowsiness, when eye velocity was reduced. Firing rates of VPS units, on the other hand, were significantly reduced in the drowsy state. Lateral canal-related units had average firing rates that were linearly related to the bias or steady state level of horizontal eye velocity during OVAR over a range of +/- 60 deg/s. These units could be further divided into two classes according to whether they were modulated during OVAR. Non-modulated units (n = 5) were VO types and all modulated units (n = 5) were VPS types. There was no significant difference between the bias level sensitivities relative to eye velocity of the units with and without modulation (P > 0.05). The modulated units had no sustained change in

  17. 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.

  18. Effects of ovariectomy on GnRH neuronal morphology in rhesus monkey (Macaca mulatta).

    PubMed

    Witkin, J W

    1996-08-01

    Gonadotropin releasing hormone (GnRH) neurons are typically simple, fusiform cells; however, over the course of prepubertal development increasing numbers take on a 'spiny' appearance. Following gonadectomy there is a decrease in the frequency of these spiny GnRH neurons. These observations which were made in the rat suggest that GnRH neurons are directly affected by the gonadal steroid milieu, though they do not themselves contain receptors for these steroidal hormones. In that there are important species differences in the hypothalamic-pituitary-gonadal axis between rats and primates, the present study was undertaken to determine whether a reduction in ovarian hormones would produce similar changes in the morphology of GnRH neurons in the monkey. A further aim was to determine whether such changes were localized to a specific brain region. Immunocytochemically defined GnRH neurons were compared in adult rhesus macaques which had been ovariectomized for 6 weeks to 2 years (n = 7) and intact, cycling animals (n = 8). Within the intact group, there were significantly more spiny GnRH neurons in the medial basal hypothalamus (MBH) than in the preoptic area (POA) (about 50% of the total in the MBH compared to 33% in the POA). Following ovariectomy the frequency of spiny cells in the MBH dropped to less than 30%, but was not significantly reduced in the POA. These results suggest that changes in systemic gonadal steroid levels result in changes in the morphology of GnRH neurons preferentially in the MBH, a region that is considered critical in the generation of GnRH pulsatile release in the monkey.

  19. Individual differences in the reinforcing and punishing effects of nicotine in rhesus monkeys

    PubMed Central

    Koffarnus, Mikhail N.; Winger, Gail

    2015-01-01

    Rationale 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. Objective 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. Methods 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. Results 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. Conclusion 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. PMID:25662609

  20. Abstinence from chronic cocaine self-administration alters striatal dopamine systems in rhesus monkeys.

    PubMed

    Beveridge, Thomas J R; Smith, Hilary R; Nader, Michael A; Porrino, Linda J

    2009-04-01

    Although dysregulation within the dopamine (DA) system is a hallmark feature of chronic cocaine exposure, the question of whether these alterations persist into abstinence remains largely unanswered. Nonhuman primates represent an ideal model in which to assess the effects of abstinence on the DA system following chronic cocaine exposure. In this study, male rhesus monkeys self-administered cocaine (0.3 mg/kg per injection, 30 reinforcers per session) under a fixed-interval 3-min schedule for 100 days followed by either 30 or 90 days abstinence. This duration of cocaine self-administration has been previously shown to decrease DA D2-like receptor densities and increase levels of D1-like receptors and DA transporters (DAT). Responding by control monkeys was maintained by food presentation under an identical protocol and the same abstinence periods. [(3)H]SCH 23390 binding to DA D1 receptors following 30 days of abstinence was significantly higher in all portions of the striatum, compared to control animals, whereas [(3)H]raclopride binding to DA D2 receptors was not different between groups. [(3)H]WIN 35 428 binding to DAT was also significantly higher throughout virtually all portions of the dorsal and ventral striatum following 30 days of abstinence. Following 90 days of abstinence, however, levels of DA D1 receptors and DAT were not different from control values. Although these results indicate that there is eventual recovery of the separate elements of the DA system, they also highlight the dynamic nature of these components during the initial phases of abstinence from chronic cocaine self-administration. PMID:18769473

  1. Kinetics of 11C-labeled opiates in the brain of rhesus monkeys

    SciTech Connect

    Hartvig, P.; Bergstroem, K.; Lindberg, B.; Lundberg, P.O.; Lundqvist, H.; Langstroem, B.; Svaerd, H.; Rane, A.

    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 appeared 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.

  2. Metabolism of /sup 14/C-labeled doxylamine succinate (Bendectin) in the rhesus monkey (Macaca mulatta)

    SciTech Connect

    Slikker, W. Jr.; Holder, C.L.; Lipe, G.W.; Korfmacher, W.A.; Thompson, H.C. Jr.; Bailey, J.R.

    1986-05-01

    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%); 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.

  3. 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

  4. Behavioral evaluation of modafinil and the abuse-related effects of cocaine in rhesus monkeys.

    PubMed

    Newman, Jennifer L; Negus, S Stevens; Lozama, Anthony; Prisinzano, Thomas E; Mello, Nancy K

    2010-10-01

    Modafinil is a central nervous system stimulant used to promote wakefulness, and it is being evaluated clinically as an agonist medication for treating stimulant abuse. This is the first report of the effects of modafinil on the abuse-related effects of cocaine in nonhuman primates. The behavioral effects of modafinil were examined in three studies. First, the discriminative stimulus effects of modafinil (3.2-32 mg/kg) were evaluated in rhesus monkeys (Macaca mulatta) trained to discriminate either low (0.18 mg/kg, IM) or high (0.4 mg/kg, IM) doses of cocaine from saline. Modafinil dose-dependently substituted for cocaine in 6 of 7 monkeys. In the second study, the effects of chronically administered modafinil (32-56 mg/kg/day, IV) on food- and cocaine-maintained (0.001-0.1 mg/kg/inj) operant responding were examined. Modafinil was administered 3 times/hr for 23 hr/day to ensure stable drug levels. Chronic treatment with 32 mg/kg/day modafinil selectively reduced responding maintained by intermediate and peak reinforcing doses of cocaine, but responding maintained by higher doses of cocaine was unaffected. Food-maintained behavior did not change during chronic modafinil treatment. In a third study, modafinil (32 and 56 mg/kg/day, IV) was examined in a reinstatement model. Modafinil transiently increased responding during extinction. These findings indicate that modafinil shares discriminative stimulus effects with cocaine and selectively reduces responding maintained by reinforcing doses of cocaine. In addition, modafinil reinstated cocaine-seeking behavior, which may reflect its cocaine-like discriminative stimulus effects. These data support clinical findings and indicate that these preclinical models may be useful for predicting the effectiveness of agonist medications for drug abuse treatment. PMID:20939643

  5. Assessment of environmental impacts of a colony of free-ranging rhesus monkeys (Macca mulatta) on Morgan Island, South Carolina.

    PubMed

    Klopchin, Jeanette L; Stewart, Jill R; Webster, Laura F; Sandifer, Paul A

    2008-02-01

    Morgan Island, located within the ACE Basin National Estuarine Research Reserve in South Carolina, is home to the only free-ranging colony of rhesus monkeys (Macca mulatta) in the continental United States. The purpose of this study was to assess environmental impacts of the monkey colony on water quality in adjacent tidal creeks and on island vegetation. Three tidal creeks were sampled: Morgan Creek, adjacent to the monkey colony; Back Creek, on Morgan Island not adjacent to the colony; and Rock Creek, on a nearby island unoccupied by monkeys. Temperature, salinity, pH, dissolved oxygen, nutrients and fecal coliform bacteria were measured six times at three sites in each of these creeks, and vegetation change analysis was conducted in a geographic information system using satellite imagery. Results showed elevated fecal coliform concentrations in the Morgan Creek site immediately adjacent to the colony, though no samples exceeded the standard set for recreational water use. Ribotyping reconnaissance matched four Escherichia coli isolates from Morgan and Back Creeks to the monkeys, identifying the colony as one source of fecal coliform bacteria, though relative source loadings could not be quantified. Significant differences were not observed between ammonia or orthophosphate levels in Morgan Creek relative to the other creeks tested; and vegetation change analysis showed a 35% increase in canopy cover between 1979 and 1999. Overall, these results suggest that the rhesus colony's environmental impacts are localized and minimal. Results from this study provide baseline data on Morgan Island and may be useful in management decisions regarding the future of the monkey colony. PMID:17564800

  6. Late cataractogenesis in rhesus monkeys irradiated with protons and radiogenic cataract in other species

    SciTech Connect

    Lett, J.T.; Lee, A.C.; Cox, A.B. )

    1991-05-01

    Rhesus monkeys (Macaca mulatta) which were irradiated at ca. 2 years of age with acute doses (less than or equal to 5 Gy) of protons (32-2300 MeV) are exhibiting the late progressive phase of radiation cataractogenesis 20-24 years after exposure, the period during which we have been monitoring the sequelae of irradiation of the lens. The median life span of the primate is approximately 24 years. Analogous late ocular changes also occur in a similar period of the lifetimes of New Zealand White (NZW) rabbits (Oryctolagus cuniculus) exposed at 8-10 weeks of age to 460-MeV {sup 56}Fe ions. In this experiment, which has been in progress for ca. 6 years, we are following the development of radiation-induced lenticular opacification (cataractogenic profiles) throughout the life span. The median life span of the lagomorph is 5-7 years. Cataractogenic profiles for NZW rabbits irradiated with {sup 20}Ne and {sup 40}Ar ions and {sup 60}Co gamma photons were obtained previously. Reference is also made to measurements of the cataractogenic profiles of a short-lived rodent, the Fischer 344 rat (Rattus norvegicus) during the first year after exposure at 8-10 weeks of age to spread-Bragg-peak protons of 55 MeV nominal energy. The median life span of the rodent is reported to be 2-3 years.

  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. PMID:21922250

  8. Evidence of temporal cortical dysfunction in rhesus monkeys following chronic cocaine self-administration.

    PubMed

    Liu, S; Heitz, R P; Sampson, A R; Zhang, W; Bradberry, C W

    2008-09-01

    Cocaine abusers show impaired performance on cognitive tasks that engage prefrontal cortex. These deficits may contribute to impaired control and relapse in abusers. Understanding the neuronal substrates that lead to these deficits requires animal models that are relevant to the human condition. However, to date, models have mostly focused on behaviors mediated by subcortical systems. Here we evaluated the impact of long-term self-administration of cocaine in the rhesus monkey on cognitive performance. Tests included stimulus discrimination (SD)/reversal and delayed alternation tasks. The chronic cocaine animals showed marked deficits in ability to organize their behavior for maximal reward. This was demonstrated by an increased time needed to acquire SDs. Deficits were also indicated by an increased time to initially learn the delayed alternation task, and to adapt strategies for bypassing a reliance on working memory to respond accurately. Working memory per se (delay dependent performance) was not affected by chronic self-administration. This pattern of cognitive deficits suggests dysfunction that extends beyond localized prefrontal cortical areas. In particular, it appears that temporal cortical function is also compromised. This agrees with other recent clinical and preclinical findings, and suggests further study into addiction related dysfunction across more widespread cortical networks is warranted. PMID:18096561

  9. New noninvasive imaging technique for cataract evaluation in the rhesus monkey

    NASA Astrophysics Data System (ADS)

    DiCarlo, Cheryl D.; Boppart, Stephen A.; Gagliano, Donald A.; Amnotte, Rodney E.; Smith, Audrey B.; Hammer, Daniel X.; Cox, Ann B.; Hee, Michael R.; Fujimoto, James G.; Swanson, Eric A.; Roach, William P.

    1995-05-01

    We present the first in vivo study using Optical Coherence Tomography (OCT) as the imaging device for lenticular cataracts in the geriatric rhesus monkey. OCT is a non-invasive imaging technique that produces a 2D cross sectional image of intraocular tissue similar to ultrasound B scan. In OCT the images are formed by measuring optical reflections from the tissue. Eighteen geriatric subjects with documented lenticular opacities and one control subject were imaged. The OCT images produced are compared to current and previous clinical cataract grading exams and slit-lamp photography. Histopathology was collected on one subject and is compared to the OCT image. OCT provides information on nuclear, cortical and subcapsular opacities. The image formation is presented based on a color coded computer generated log reflective scale. The log reflective scale is converted to a qualitative grading system. Although movement and shadow artifact can occur, these are readily identifiable and can be differentiated from underlying lenticular abnormalities. OCT has great potential to assist in further characterization of cataracts.

  10. Transient reinforcing effects of phenylisopropylamine and indolealkylamine hallucinogens in rhesus monkeys.

    PubMed

    Fantegrossi, W E; Woods, J H; Winger, G

    2004-03-01

    Relatively few studies have assessed the reinforcing effects of hallucinogenic compounds, and no such studies have attempted to engender contingent responding for these compounds in animals with behavioral histories that include experience with serotonergically mediated reinforcing effects. The objectives of the present study were to investigate the capacity of several hallucinogenic compounds to maintain self-administration behavior in rhesus monkeys with a previous history of 3,4-methylenedioxymethamphetamine (MDMA) self-administration, and to compare these effects across a range of doses of drugs from two structural classes (indolealkylamines and phenylisopropylamines). The results indicate that no compound generated reliable responding and that no subject ever self-administered 4-iodo-2,5-dimethoxyphenylisopropylamine (DOI) at rates above those engendered by contingent saline. However, 3 out of 4 subjects did respond at rates between 0.75 and 3.0 responses/s in one or more sessions where N,N-dimethyltryptamine (DMT), mescaline or psilocybin were available. During some of these sessions in which self-administration was maintained, animals earned a majority of all available infusions and appeared intoxicated by the end of the session. This pattern of transient self-administration may indicate that these compounds have weak reinforcing effects, or mixed reinforcing and aversive effects.

  11. Protective efficacy of a global HIV-1 mosaic vaccine against heterologous SHIV challenges in rhesus monkeys.

    PubMed

    Barouch, Dan H; Stephenson, Kathryn E; Borducchi, Erica N; Smith, Kaitlin; Stanley, Kelly; McNally, Anna G; Liu, Jinyan; Abbink, Peter; Maxfield, Lori F; Seaman, Michael S; Dugast, Anne-Sophie; Alter, Galit; Ferguson, Melissa; Li, Wenjun; Earl, Patricia L; Moss, Bernard; Giorgi, Elena E; Szinger, James J; Eller, Leigh Anne; Billings, Erik A; Rao, Mangala; Tovanabutra, Sodsai; Sanders-Buell, Eric; Weijtens, Mo; Pau, Maria G; Schuitemaker, Hanneke; Robb, Merlin L; Kim, Jerome H; Korber, Bette T; Michael, Nelson L

    2013-10-24

    The global diversity of HIV-1 represents a critical challenge facing HIV-1 vaccine development. HIV-1 mosaic antigens are bioinformatically optimized immunogens designed for improved coverage of HIV-1 diversity. However, the protective efficacy of such global HIV-1 vaccine antigens has not previously been evaluated. Here, we demonstrate the capacity of bivalent HIV-1 mosaic antigens to protect rhesus monkeys against acquisition of infection following heterologous challenges with the difficult-to-neutralize simian-human immunodeficiency virus SHIV-SF162P3. Adenovirus/poxvirus and adenovirus/adenovirus vector-based vaccines expressing HIV-1 mosaic Env, Gag, and Pol afforded a significant reduction in the per-exposure acquisition risk following repetitive, intrarectal SHIV-SF162P3 challenges. Protection against acquisition of infection correlated with vaccine-elicited binding, neutralizing, and functional nonneutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. These data demonstrate the protective efficacy of HIV-1 mosaic antigens and suggest a potential strategy for the development of a global HIV-1 vaccine. PAPERCLIP:

  12. Eruption of permanent dentition in rhesus monkeys exposed to ELF (extremely low frequency) fields. Interim report

    SciTech Connect

    David, T.D.; Harris, G.A.; Bley, J.A. Jr

    1983-04-01

    In a study initiated to determine the biological effects of ELF electric and magnetic fields associated with a submarine communications system ELF-exposed male rhesus monkeys gained weight at a slightly faster rate than control males. In order to obtain sufficient data on the physiological effects of electromagnetic fields, a second ELF study was initiated. Whereas the first study was initiated with wild-caught young adult animals, the second study utilized colony-bred animals beginning at 30 days of age. The emphasis of the second study was to substantiate previous findings and determine the underlying mechanisms involved. As in the first study, 30 primates (male and female) were exposed to the ELF electric and magnetic fields, and 30 control animals received the same care and treatment, but were not exposed. This report deals with the development of the permanent teeth relative to ELF exposure and sex. A consistent trend noted was that the teeth of female animals erupted at a slightly earlier age than males. However, no significant differences due to ELF exposure or sex were detected.

  13. Comparison of the transplacental pharmacokinetics of cortisol and triamcinolone acetonide in the rhesus monkey

    SciTech Connect

    Slikker, W. Jr.; Althaus, Z.R.; Rowland, J.M.; Hill, D.E.; Hendrickx, A.G.

    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-min 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.

  14. Delay discounting of food by rhesus monkeys: Cocaine and food choice in isomorphic and allomorphic situations.

    PubMed

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

    2015-06-01

    Research on delay discounting has focused largely on nondrug reinforcers in an isomorphic context in which choice is between alternatives that involve the same type of reinforcer. Less often, delay discounting has been studied with drug reinforcers in a more ecologically valid allomorphic context where choice is between alternatives involving different types of reinforcers. The present experiment is the first to examine discounting of drug and nondrug reinforcers in both isomorphic and allomorphic situations using a theoretical model (i.e., the hyperbolic discounting function) that allows for comparisons of discounting rates between reinforcer types and amounts. The goal of the current experiment was to examine discounting of a delayed, nondrug reinforcer (food) by male rhesus monkeys when the immediate alternative was either food (isomorphic situation) or cocaine (allomorphic situation). In addition, we sought to determine whether there was a magnitude effect with delayed food in the allomorphic situation. Choice of immediate food and immediate cocaine increased with amount and dose, respectively. Choice functions for immediate food and cocaine generally shifted leftward as delay increased. Compared to isomorphic situations in which food was the immediate alternative, delayed food was discounted more steeply in allomorphic situations where cocaine was the immediate alternative. Notably, discounting was not affected by the magnitude of the delayed reinforcer. These data indicate that how steeply a delayed nondrug reinforcer is discounted may depend more on the qualitative characteristics of the immediate reinforcer and less on the magnitude of the delayed one.

  15. Transplacental pharmacokinetics of cocaine and benzoylecgonine in plasma and hair of rhesus monkeys.

    PubMed

    Bailey, B; Morris, P; McMartin, K I; Klein, J; Duhart, H M; Gillam, M P; Binienda, Z; Slikker, W; Paule, M G; Koren, G

    1998-01-01

    There is large variability in the rate and extent of fetal damage from cocaine in humans; however, the sources of such variability are not presently known. In order to study the relationship between maternal cocaine pharmacokinetics at the end of pregnancy and maternal or infant cocaine and benzoylecgonine hair concentrations at birth, ten rhesus monkeys were administered cocaine intramuscularly throughout pregnancy. Cocaine and benzoylecgonine hair concentrations were determined at birth and correlated with maternal pharmacokinetics during pregnancy. There were no correlations between either maternal cocaine Cmax or AUC0-infinity and maternal and infant hair cocaine or benzoylecgonine concentrations. There were no significant correlations between maternal hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.60; P = 0.07) or benzoylecgonine Cmax (r = 0.60; P = 0.07). No correlations existed between infant hair benzoylecgonine concentrations and either maternal benzoylecgonine AUC0-120 (r = 0.30; P = 0.40) or benzoylecgonine Cmax (r = 0.30; P = 0.40). Also, no correlation was found between maternal cocaine dose and maternal or infant cocaine and benzoylecgonine hair concentrations. In comparison to toxicants such as nicotine and carbon monoxide for which there is a good correlation between maternal systemic exposure and neonatal concentrations, the lack of a similar relationship for cocaine is consistent with the role of the placenta in contributing to the variability in the amounts of cocaine reaching the fetus and hence, potentially to the risk of adverse fetal outcome.

  16. Disposition of the radioprotector ethiofos in the rhesus monkey. Influence of route of administration

    SciTech Connect

    Mangold, D.J.; Miller, M.A.; Huelle, B.K.; Sanchez-Barona, D.O.; Swynnerton, N.F.; Fleckenstein, L.; Ludden, T.M. )

    1989-05-01

    Plasma concentrations of ethiofos (S-2-(3-aminopropylamino)ethyl phosphorothioic acid, WR-2721) were compared following iv, ip, intraduodenal, and portal administration to the rhesus monkey. Plasma samples were analyzed for ethiofos, free WR-1065, (2-(3-aminopropylamino)ethanethiol), and total material convertible to WR-1065 (total WR-1065). In separate experiments, total radioactivity in plasma was compared following iv, ip, and intraduodenal administration of ({sup 14}C)ethiofos; excretion of the radiolabel was measured in urine and in feces. Intraduodenal administration of unlabeled ethiofos rarely gave measurable levels of unchanged drug in plasma. In contrast, intraduodenal administration of ({sup 14}C)ethiofos produced an average AUC for total radioactivity that was 62% of that for a 10-min iv infusion of ({sup 14}C)ethiofos. Urinary excretion of radioactivity following iv and intraduodenal administration of ({sup 14}C)ethiofos was 78.9 +/- 14.0% and 43.8 +/- 12.4%, respectively, whereas 1.9 +/- 0.5% and 9.7 +/- 6.3% was excreted in feces. After an ip dose of either labeled or unlabeled ethiofos, absorption of the dose was prolonged, but AUC values for total radioactivity or ethiofos and total WR-1065 were similar to those observed after the corresponding 10-min iv experiments. For either iv or portal routes, increases in ethiofos AUC values were observed for the same total dose when the infusion rate was increased from 1.25 to 15 mg/kg/min.

  17. Acute effects of nalmefene on LH, prolactin, and testosterone in male rhesus monkeys.

    PubMed

    Mello, N K; Mendelson, J H; Kelly, M

    2000-06-01

    The effects of the long-acting opioid antagonist, nalmefene [17-N-cyclopropylmethyl-3,14-beta-dihydroxy-4, 5-alpha-epoxy-6-methylene morphinan hydrochloride] on LH, T, and prolactin release in rhesus monkeys are unknown. The acute effects of nalmefene (0.01 and 0.10 mg/kg, IV) or placebo on LH, PRL, and T were studied, and samples were collected at 10-min intervals for 360 min to permit cluster analysis of pulsatile release patterns. LH increased significantly within 30 min after nalmefene, and remained significantly above baseline levels for 50 to 60 min (p < 0.05). Testosterone increased significantly within 70 to 80 min after nalmefene, and remained significantly above baseline for 60 min (p < 0.05). Although nalmefene antagonizes opioid agonists for 6-8 h, inhibitory feedback by testosterone appeared to limit the duration of its antagonism of endogenous opioid inhibition of LHRH and stimulation of LH. Nalmefene did not change LH or PRL pulse frequency or amplitude significantly in comparison to placebo administration. PMID:10880679

  18. Effects of opiate antagonists on hormones and behavior of male and female rhesus monkeys.

    PubMed

    Abbott, D H; Holman, S D; Berman, M; Neff, D A; Goy, R W

    1984-02-01

    Opiate antagonists, naloxone (100 micrograms/kg) and naltrexone (1 mg/kg) were given to singly housed adult male or female rhesus prior to a 20-minute behavioral test with an oppositely sexed stimulus monkey. Four of the intact adult males were socially and sexually experienced. The remaining two intact males and two castrated males had been reared in socially restricted conditions and were psychosexually deficient. Adult females were ovariectomized, and the effects of opiate antagonists were examined with or without concurrent estradiol treatment. Both antagonists inhibited sexual behavior of the socially reared, sexually active, intact males. No stimulatory effects on sexual behavior were observed for sexually deficient males, whether intact or castrated. Females showed little change in sexual behavior following opiate antagonist treatment, regardless of endocrine status. The proportion of approaches of the female to the male was increased when naloxone, but not naltrexone, was given. Specific endocrine effects of the opiate antagonists were only found in intact males. Naltrexone significantly increased LH concentrations in the two males tested, while the increase in LH in the four males receiving naloxone was not significant. In all intact males, increases in LH were accompanied by statistically significant increases in circulating concentrations of testosterone following naloxone and naltrexone. The gonadotropic stimulating effect of the opiate antagonists was specific to LH, and no changes were observed in circulating concentrations of FSH in either sex. PMID:6424632

  19. Acute effects of nalmefene on LH, prolactin, and testosterone in male rhesus monkeys.

    PubMed

    Mello, N K; Mendelson, J H; Kelly, M

    2000-06-01

    The effects of the long-acting opioid antagonist, nalmefene [17-N-cyclopropylmethyl-3,14-beta-dihydroxy-4, 5-alpha-epoxy-6-methylene morphinan hydrochloride] on LH, T, and prolactin release in rhesus monkeys are unknown. The acute effects of nalmefene (0.01 and 0.10 mg/kg, IV) or placebo on LH, PRL, and T were studied, and samples were collected at 10-min intervals for 360 min to permit cluster analysis of pulsatile release patterns. LH increased significantly within 30 min after nalmefene, and remained significantly above baseline levels for 50 to 60 min (p < 0.05). Testosterone increased significantly within 70 to 80 min after nalmefene, and remained significantly above baseline for 60 min (p < 0.05). Although nalmefene antagonizes opioid agonists for 6-8 h, inhibitory feedback by testosterone appeared to limit the duration of its antagonism of endogenous opioid inhibition of LHRH and stimulation of LH. Nalmefene did not change LH or PRL pulse frequency or amplitude significantly in comparison to placebo administration.

  20. Studies of marginal zinc deprivation in rhesus monkeys. V. Fetal and infant skeletal effects.

    PubMed

    Leek, J C; Vogler, J B; Gershwin, M E; Golub, M S; Hurley, L S; Hendrickx, A G

    1984-12-01

    Skeletal maturation was evaluated in newborn and infant rhesus monkeys that had been subjected to a marginally zinc-deficient diet (4 ppm zinc) from conception through 12 months of postnatal life. Serial radiographic assessment of skeletal development was performed and compared to both ad libitum and pair-fed controls. Radiographs were obtained at birth and at 1, 3, 9, and 12 months of age. In each age group a maturation indicator was selected to identify individuals with abnormal skeletal maturation defined on the basis of presence of epiphyseal ossification centers. Animals were compared only within a given sex group. Additionally, to evaluate endochondral bone mineralization, the appearance of the zone of provisional calcification on the metaphyseal side of the growth plate and the width of the growth plate were assessed. A marginal level of zinc deprivation during gestation and during the 1st yr of life was found to be associated with significantly delayed skeletal maturation and defective mineralization. This abnormality of bone mineralization has many features similar to human rachitic syndromes and suggests that zinc plays an important role in endochondral bone formation.

  1. Relative reinforcing effects of cocaine, remifentanil, and their combination in rhesus monkeys.

    PubMed

    Winger, G; Galuska, C M; Hursh, S R; Woods, J H

    2006-07-01

    Human polydrug abusers often take combinations of opioids and stimulants, but it is not clear why. Behavioral economics with demand curve analysis is uniquely able to separate two of the possibilities: that the drug combination increases the reinforcing potency of the component drugs or that the drug combination is a more effective reinforcer than either drug alone. Rhesus monkeys self-administered a range of doses of cocaine, remifentanil, and combinations of the drugs through indwelling intravenous catheters; the number of responses required for each drug infusion increased across drug-availability sessions. Combining small doses of cocaine and remifentanil that by themselves resulted in very low rates of responding yielded rates of responding that were higher than the maximum maintained by any dose of the constituent drugs. Nevertheless, demand curve analysis demonstrated that the drug combination was equally elastic as the component drugs, indicating that it was not more effective as a reinforcer than either cocaine or remifentanil alone. This suggests that enhanced self-administration of this particular drug combination is due primarily to the drug enhancement of the potency of the other drug. PMID:16571623

  2. Quantification of drug choice with the generalized matching law in rhesus monkeys.

    PubMed

    Koffarnus, Mikhail N; Woods, James H

    2008-03-01

    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 methohexital), and between drug and drug-paired stimuli. The bias parameter of the generalized matching law was used to quantify preference for one reinforcer over another. Choice between identical drug doses yielded undermatching. Choices between 0.3 microg/kg/injection remifentanil and either 0.1 microg/kg/injection remifentanil or saline plus drug-paired stimuli revealed bias for the 0.3 microg/kg/injection dose. Choice was relatively insensitive to differences in random interval schedule value when one reinforcer was replaced with drug-paired stimulus presentations. Bias for 0.3 microg/kg/injection remifentanil over 10 microg/kg/injection cocaine was seen in one subject, and indifference was generally observed between 0.1 microg/kg/injection remifentanil and 56 microg/kg/injection cocaine and between 30 microg/kg/injection cocaine and 320 microg/kg/injection methohexital. These findings suggest the bias parameter may be useful in quantitatively measuring level of preference, which would be an advantage over concurrent FR procedures that often result in exclusive choice. PMID:18422019

  3. 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.

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

    SciTech Connect

    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 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. 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).

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

    SciTech Connect

    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 life 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.

  6. 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

  7. Architecture and connections of retrosplenial area 30 in the rhesus monkey (Macaca mulatta).

    PubMed

    Morris, R; Petrides, M; Pandya, D N

    1999-07-01

    Because of the sharp curvature of the retrosplenial region around the splenium of the corpus callosum, standard coronal sections are not appropriate for architectonic analysis of its posteroventral part. In the present study, examination of the posteroventral retrosplenial region of the rhesus monkey in sections that were orthogonal to its axis of curvature (and therefore appropriate for architectonic analysis) has permitted definition of its architecture and precise extent. This analysis demonstrated that areas 29 and 30 of the retrosplenial cortex, as well as adjacent area 23 of the posterior cingulate cortex, extend together as an arch around the splenium of the corpus callosum and maintain their topographical relationship with one another throughout their entire course. Injections of anterograde and retrograde tracers confined to retrosplenial area 30 revealed that this area has reciprocal connections with adjacent areas 23, 19 and PGm, with the mid-dorsolateral part of the prefrontal cortex (areas 9, 9/46 and 46), with multimodal area TPO in the superior temporal sulcus, as well as the posterior parahippocampal cortex, the presubiculum and the entorhinal cortex. There are also bidirectional connections with the lateroposterior thalamic nucleus, as well as the laterodorsal and the anteroventral limbic thalamic nuclei. The connectivity of area 30 suggests that it may play a role in working memory processes subserved by the mid-dorsolateral frontal cortex in interaction with the hippocampal system.

  8. Identifying individual differences of fluoxetine response in juvenile rhesus monkeys by metabolite profiling

    PubMed Central

    He, Y; Hogrefe, C E; Grapov, D; Palazoglu, M; Fiehn, O; Turck, C W; Golub, M S

    2014-01-01

    Fluoxetine is the only psychopharmacological agent approved for depression by the US Food and Drug Administration for children and is commonly used therapeutically in a variety of neurodevelopmental disorders. Therapeutic response shows high individual variability, and severe side effects have been observed. In the current study we set out to identify biomarkers of response to fluoxetine as well as biomarkers that correlate with impulsivity, a measure of reward delay behavior and potential side effect of the drug, in juvenile male rhesus monkeys. The study group was also genotyped for polymorphisms of monoamine oxidase A (MAOA), a gene that has been associated with psychiatric disorders. We used peripheral metabolite profiling of blood and cerebrospinal fluid (CSF) from animals treated daily with fluoxetine or vehicle for one year. Fluoxetine response metabolite profiles and metabolite/reward delay behavior associations were evaluated using multivariate analysis. Our analyses identified a set of plasma and CSF metabolites that distinguish fluoxetine- from vehicle-treated animals and metabolites that correlate with impulsivity. Some metabolites displayed an interaction between fluoxetine and MAOA genotype. The identified metabolite biomarkers belong to pathways that have important functions in central nervous system physiology. Biomarkers of response to fluoxetine in the normally functioning brain of juvenile nonhuman primates may aid in finding predictors of response to treatment in young psychiatric populations and in progress toward the realization of a precision medicine approach in the area of neurodevelopmental disorders. PMID:25369145

  9. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    PubMed

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction.

  10. Acute brain metabolic effects of cocaine in rhesus monkeys with a history of cocaine use.

    PubMed

    Henry, Porche' Kirkland; Murnane, Kevin S; Votaw, John R; Howell, Leonard L

    2010-12-01

    Cocaine addiction involves an escalation in drug intake which alters many brain functions. The present study documented cocaine-induced changes in brain metabolic activity as a function of cocaine self-administration history. Experimentally naive rhesus monkeys (N = 6) were given increasing access to cocaine under a fixed-ratio schedule of intravenous (i.v.) drug self-administration. PET imaging with F-18 labeled fluorodeoxyglucose (FDG) was used to measure acute intramuscular (i.m.) cocaine-induced changes in brain metabolism in the cocaine-naïve state, following 60 sessions under limited-access conditions (1 h/day), following 60 sessions under extended-access conditions (4 h/day), and following 4 weeks of drug withdrawal. In the cocaine-naïve state, cocaine-induced increases in brain metabolism were restricted to the prefrontal cortex. As cocaine exposure increased from limited to extended access, metabolic effects expanded throughout the frontal cortex and were induced within the striatum. Conversely, cocaine-induced activation was far less robust following withdrawal. The results highlight a progressive expansion of the metabolic effects of cocaine to include previously unaffected dopamine innervated brain regions as a consequence of cocaine self-administration history. The identification of brain regions progressively influenced by drug exposure may be highly relevant toward efforts to develop treatments for cocaine addiction. PMID:20680706

  11. Delay discounting of food by rhesus monkeys: Cocaine and food choice in isomorphic and allomorphic situations.

    PubMed

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

    2015-06-01

    Research on delay discounting has focused largely on nondrug reinforcers in an isomorphic context in which choice is between alternatives that involve the same type of reinforcer. Less often, delay discounting has been studied with drug reinforcers in a more ecologically valid allomorphic context where choice is between alternatives involving different types of reinforcers. The present experiment is the first to examine discounting of drug and nondrug reinforcers in both isomorphic and allomorphic situations using a theoretical model (i.e., the hyperbolic discounting function) that allows for comparisons of discounting rates between reinforcer types and amounts. The goal of the current experiment was to examine discounting of a delayed, nondrug reinforcer (food) by male rhesus monkeys when the immediate alternative was either food (isomorphic situation) or cocaine (allomorphic situation). In addition, we sought to determine whether there was a magnitude effect with delayed food in the allomorphic situation. Choice of immediate food and immediate cocaine increased with amount and dose, respectively. Choice functions for immediate food and cocaine generally shifted leftward as delay increased. Compared to isomorphic situations in which food was the immediate alternative, delayed food was discounted more steeply in allomorphic situations where cocaine was the immediate alternative. Notably, discounting was not affected by the magnitude of the delayed reinforcer. These data indicate that how steeply a delayed nondrug reinforcer is discounted may depend more on the qualitative characteristics of the immediate reinforcer and less on the magnitude of the delayed one. PMID:25938515

  12. 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. PMID:22968813

  13. 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

  14. Asymmetric generalization and interaction profiles in rhesus monkeys discriminating intravenous cocaine or intravenous heroin from vehicle.

    PubMed

    Platt, Donna M; Rowlett, James K; Spealman, Roger D

    2010-03-01

    Many polydrug abusers combine cocaine with heroin in the form of a "speedball." This study investigated the discriminative stimulus (DS) effects of speedballs in rhesus monkeys trained to discriminate either intravenous cocaine or intravenous heroin from vehicle. Initial substitution tests revealed an asymmetry in the generalization profile of dopamine and opioid agonists such that mu agonists partially substituted for cocaine, but direct and indirect dopamine agonists did not substitute for heroin. Subsequent speedball tests in which drug mixtures were administered by coinjecting the component drugs while keeping the dose-ratio constant revealed an additional asymmetry. In cocaine-trained monkeys, coadministration of cocaine and heroin produced leftward shifts in the cocaine dose-response function. Heroin's cocaine-enhancing effects were mimicked by the mu agonists fentanyl and methadone and less consistently by the delta agonist (+)-4-[(alphaR)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide (SNC 80) and reversed by the mu antagonist naltrexone and the delta antagonist naltrindole. In heroin-trained monkeys, coadministration of cocaine and heroin attenuated the DS effects of heroin. Cocaine's heroin-attenuating effects were mimicked by the D1-like agonist 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine (SKF 81297) and the D2-like agonist R-(-)-propylnorapomorphine and reversed by the D1-like antagonist (6aS-trans)-11-chloro-6,6a,7,8,9,13b-hexahydro-7-methyl-5H- benzo[d] aphtha[2,1-b]azepin-12-ol hydrobromide (SCH 39166) and the D2-like antagonist raclopride. Attenuation of the effects of heroin was accompanied by decreases in response rate. These results suggest that heroin enhances the DS effects of cocaine via mu, and to a lesser extent delta, receptor mechanisms; whereas cocaine-induced inhibition of the DS effects of heroin probably was due at least in part to masking of the heroin DS presumably

  15. Immunogenicity and protective efficacy of a recombinant subunit West Nile virus vaccine in rhesus monkeys.

    PubMed

    Lieberman, Michael M; Nerurkar, Vivek R; Luo, Haiyan; Cropp, Bruce; Carrion, Ricardo; de la Garza, Melissa; Coller, Beth-Ann; Clements, David; Ogata, Steven; Wong, Teri; Martyak, Tim; Weeks-Levy, Carolyn

    2009-09-01

    The immunogenicity and protective efficacy of a recombinant subunit West Nile virus (WNV) vaccine was evaluated in rhesus macaques (Macaca mulatta). The vaccine consisted of a recombinant envelope (E) protein truncated at the C-terminal end, resulting in a polypeptide containing 80% of the N-terminal amino acids of the native WNV protein (WN-80E), mixed with an adjuvant (GPI-0100). WN-80E was produced in a Drosophila melanogaster expression system with high yield and purified by immunoaffinity chromatography using a monoclonal antibody specific for flavivirus E proteins. Groups of monkeys were vaccinated with formulations containing 1 or 25 microg of WN-80E antigen, and both humoral and cellular immunity were assessed after vaccination. The results demonstrated potent antibody responses to vaccination, as determined by both enzyme-linked immunosorbent assay and virus-neutralizing antibody assays. All vaccinated animals responded favorably, and there was little difference in response between animals immunized with 1 or 25 microg of WN-80E. Cellular immunity was determined by lymphocyte proliferation and cytokine production assays using peripheral blood mononuclear cells from vaccinated animals stimulated in vitro with WN-80E. Cell-mediated immune responses varied from animal to animal within each group. About half of the animals responded with lymphoproliferation, cytokine production, or both. Again, there was little difference in response between animals immunized with a 1- or 25-microg dose of WN-80E in the vaccine formulations. In a separate experiment, groups of monkeys were immunized with the WN-80E/GPI-0100 vaccine or an adjuvant-only control formulation. Animals were then challenged by inoculation of wild-type WNV, and the level of viremia in each animal was monitored daily for 10 days. The results showed that whereas all animals in the control group had detectable viremia for at least 3 days after challenge, all of the vaccinated animals were negative on all

  16. Characterization of the 10q26-orthologue in rhesus monkeys corroborates a functional connection between ARMS2 and HTRA1.

    PubMed

    Pahl, Lisa; Spangenberg, Astrid; Schubert, Stephanie; Schönmann, Uwe; Schmidtke, Jörg; Stuhrmann, Manfred

    2012-05-01

    Age-related macular degeneration, which is the leading cause of blindness in industrialized countries, is a multifactorial, degenerative disorder of the macula with strong heritability. For age-related macular degeneration in humans, the genes ARMS2 and HTRA1 in the region 10q26 are both promising candidates for being involved in pathogenesis. However, the associated variants are located in a region of strong linkage disequilibrium and so far, the identification of the causative gene in humans was not yet possible. This dilemma might be solved using an appropriate model organism. Rhesus monkeys suffer from drusen, a major hallmark of age-related macular degeneration, and the drusen-phenotype shares susceptibility factors with human macular degeneration. Thus, the rhesus monkey represents a natural animal model to uncover genetic factors leading to macular degeneration. Moreover, the existence of genetically homogenous cohorts offers an excellent opportunity to determine risk factors. However, the 10q26-orthologue genomic region in rhesus monkeys is not characterized in detail so far. Therefore, the aim of this study is to analyze the rhesus linkage disequilibrium structure and to investigate whether variants in ARMS2 or HTRA1 are associated with the drusen-phenotype as well. We sequenced parts of a 20 kb region around ARMS2 and HTRA1 in a genetically homogeneous cohort of 91 rhesus monkeys descending from the CPRC rhesus cohort on Cayo Santiago and currently housed in the German Primate Centre in Göttingen. Within this group, ophthalmoscopic examinations revealed a naturally high drusen prevalence of about 47% in monkeys >5 years. We detected 56 genetic variants within and around ARMS2 and HTRA1 and, as one deviates from Hardy-Weinberg-Equilibrium, 55 polymorphisms were used to generate a linkage disequilibrium-Plot and to perform association studies. We observed strong linkage disequilibrium between the markers and were able to define two haplotype blocks. One of

  17. Biobehavioral consequences of prenatal exposure to a matrilineal overthrow and relocation in captive infant rhesus (Macaca mulatta) monkeys.

    PubMed

    Herrington, Joshua A; Del Rosso, Laura A; Capitanio, John P

    2016-09-01

    There is a general consensus that perinatal experiences help to shape infant behavior; however, relatively little is known about the effects of prenatal experience on postnatal phenotype in non-human primates. The current study sought to take advantage of a naturally occurring incident in a captive population of rhesus monkeys. Following a matrilineal overthrow in an outdoor field cage, pregnant female rhesus macaques were relocated from outdoor to indoor housing. Using data collected from the California National Primate Research Center's Biobehavioral Assessment Program, we assessed infants born to mothers that were in their first or second trimester of pregnancy during the overthrow and relocation, and compared their data with that of animals from two control groups born in the same year: indoor mother raised infants and field cage reared infants. Our results suggest that the experience of an overthrow and relocation during the first trimester elevated postnatal emotional responsiveness, while the same experience in the second trimester resulted in modified HPA axis regulation, elevated glucocorticoid output following maternal separation, and lower hematocrit levels compared to control groups. These data add to a growing body of literature that prenatal experiences represent a significant contribution to postnatal phenotypic variability. Findings such as ours have implications for studies in captive management and the management of captive rhesus monkey populations. Am. J. Primatol. 78:895-903, 2016. © 2016 Wiley Periodicals, Inc. PMID:27150125

  18. Rhesus monkey alpha7 nicotinic acetylcholine receptors: comparisons to human alpha7 receptors expressed in Xenopus oocytes.

    PubMed

    Papke, Roger L; McCormack, Thomas J; Jack, Brian A; Wang, Daguang; Bugaj-Gaweda, Bozena; Schiff, Hillary C; Buhr, Joshua D; Waber, Amanda J; Stokes, Clare

    2005-11-01

    An alpha7 nicotinic acetylcholine receptor sequence was cloned from Rhesus monkey (Macaca mulatta). This clone differs from the mature human alpha7 nicotinic acetylcholine receptor in only four amino acids, two of which are in the extracellular domain. The monkey alpha7 nicotinic receptor was characterized in regard to its functional responses to acetylcholine, choline, cytisine, and the experimental alpha7-selective agonists 4OH-GTS-21, TC-1698, and AR-R17779. For all of these agonists, the EC(50) for activation of monkey receptors was uniformly higher than for human receptors. In contrast, the potencies of mecamylamine and MLA for inhibiting monkey and human alpha7 were comparable. Acetylcholine and 4OH-GTS-21 were used to probe the significance of the single point differences in the extracellular domain. Mutants with the two different amino acids in the extracellular domain of the monkey receptor changed to the corresponding sequence of the human receptor had responses to these agonists that were not significantly different in EC(50) from wild-type human alpha7 nicotinic receptors. Monkey alpha7 nicotinic receptors have a serine at residue 171, while the human receptors have an asparagine at this site. Monkey S171N mutants were more like human alpha7 nicotinic receptors, while mutations at the other site (K186R) had relatively little effect. These experiments point toward the basic utility of the monkey receptor as a model for the human alpha7 nicotinic receptor, albeit with the caveat that these receptors will vary in their agonist concentration dependency. They also point to the potential importance of a newly identified sequence element for modeling the specific amino acids involved with receptor activation. PMID:16266703

  19. Pervasive alterations of emotional and neuroendocrine responses to an acute stressor after neonatal amygdala lesions in rhesus monkeys

    PubMed Central

    Raper, Jessica; Wilson, Mark; Sanchez, Mar; Machado, Christopher J.; Bachevalier, Jocelyne

    2012-01-01

    The current study examined the long-term effects of neonatal amygdala lesions on emotional and hypothalamic-pituitary-adrenal (HPA) axis reactivity to an acute stressor in rhesus monkeys. Rhesus monkeys received either bilateral MRI-guided ibotenic acid amygdala (Neo-Aibo; n = 6) or sham (Neo-C; n = 7) lesions between 7–14 days of age. Emotional reactivity was assessed using the Human Intruder paradigm at 2 months, 4.5 months, and 6–8 years of age, whereas stress neuroendocrine response was only assessed in adulthood (6–8 years). The modulation of defensive and emotional behaviors based on the gaze direction of the intruder emerged between 2–4 months of age in surrogate-peer reared sham-operated infant monkeys, as already shown for mother-reared infants. Although neonatal amygdala lesions did not impair the ability to exhibit defensive and emotional behaviors, it altered the modulation of these responses based on the intruder’s gaze direction. The changes in emotional reactivity after neonatal amygdala lesions emerged in infancy and persisted throughout adulthood when they were associated with a reduction of basal cortisol levels and a blunted cortisol response to the stressor. These changes are reminiscent of those found after adult-onset amygdala lesions, demonstrating little functional compensation following early amygdala damage. PMID:23148887

  20. Assessing the Value of Television as Environmental Enrichment for Individually Housed Rhesus Monkeys: A Behavioral Economic Approach.

    PubMed

    Harris, Linda D.; Briand, Edward J.; Orth, Rushawn; Galbicka, Gregory

    1999-03-01

    The goal of this study was to evaluate television as a source of environmental enrichment for individually housed rhesus monkeys (Macaca mulatta) by using the concepts of behavioral economics. Phase I entailed the use of operant conditioning to assess the behavior of eight rhesus monkeys given the opportunity to control their environment through lever activation of a television (TV). Success in shaping was variable, and only two animals successfully acquired lever pressing. Phase II used an alternating reinforcement/ extinction procedure as a control method to determine the degree to which lever pressing depended on TV presentation. Both animals responded with more lever pressing on the days when lever pressing produced TV. The first animal, tested with the alternating reinforcement/extinction procedure for 12 weeks yielded a mean significant difference of 3.85 (p = 0.036); the second assessed for 9 weeks was associated with a mean significant difference of 6.0 (p = 0.018). Therefore, TV (and not lever pressing itself) was positively reinforcing. The final phase of the study progressively increased the fixed ratio (FR) from 1 to 8. Linear regression of the data points, plotted as the log of price (or FR) vs the consumption of TV, revealed a significantly negative slope (-2.179, p, 0.05) and accounted for 89% of the variance. The negative demand curve suggested that TV is not a valued commodity and is highly elastic. TV provided to individually housed rhesus monkeys appears to be a weakly positive reinforcer for some animals, which may contribute to overall environmental enrichment.

  1. Assessing the Value of Television as Environmental Enrichment for Individually Housed Rhesus Monkeys: A Behavioral Economic Approach.

    PubMed

    Harris, Linda D.; Briand, Edward J.; Orth, Rushawn; Galbicka, Gregory

    1999-03-01

    The goal of this study was to evaluate television as a source of environmental enrichment for individually housed rhesus monkeys (Macaca mulatta) by using the concepts of behavioral economics. Phase I entailed the use of operant conditioning to assess the behavior of eight rhesus monkeys given the opportunity to control their environment through lever activation of a television (TV). Success in shaping was variable, and only two animals successfully acquired lever pressing. Phase II used an alternating reinforcement/ extinction procedure as a control method to determine the degree to which lever pressing depended on TV presentation. Both animals responded with more lever pressing on the days when lever pressing produced TV. The first animal, tested with the alternating reinforcement/extinction procedure for 12 weeks yielded a mean significant difference of 3.85 (p = 0.036); the second assessed for 9 weeks was associated with a mean significant difference of 6.0 (p = 0.018). Therefore, TV (and not lever pressing itself) was positively reinforcing. The final phase of the study progressively increased the fixed ratio (FR) from 1 to 8. Linear regression of the data points, plotted as the log of price (or FR) vs the consumption of TV, revealed a significantly negative slope (-2.179, p, 0.05) and accounted for 89% of the variance. The negative demand curve suggested that TV is not a valued commodity and is highly elastic. TV provided to individually housed rhesus monkeys appears to be a weakly positive reinforcer for some animals, which may contribute to overall environmental enrichment. PMID:12086433

  2. Effects of nicotinic acetylcholine receptor agonists on cognition in rhesus monkeys with a chronic cocaine self-administration history.

    PubMed

    Gould, Robert W; Garg, Pradeep K; Garg, Sudha; Nader, Michael A

    2013-01-01

    Cocaine use is associated with impaired cognitive function, which may negatively impact treatment outcomes. One pharmacological strategy to improve cognition involves nicotinic acetylcholine receptor (nAChR) stimulation. However, the effects of chronic cocaine exposure on nAChR distribution and function have not been characterized. Thus, one goal of this study was to examine nAChR availability in rhesus monkeys with an extensive cocaine self-administration history (n = 4; ~6 years, mean intake, 1463 mg/kg) compared to age-matched cocaine-naive control monkeys (n = 5). Using [¹¹C]-nicotine and positron emission tomography (PET) imaging, cocaine-experienced monkeys showed significantly higher receptor availability in the hippocampus compared to cocaine-naive monkeys. A second goal was to examine the effects of nAChR agonists on multiple domains of cognitive performance in these same monkeys. For these studies, working memory was assessed using a delayed match-to-sample (DMS) task, associative learning and behavioral flexibility using stimulus discrimination and reversal learning tasks. When administered acutely, the nonselective high-efficacy agonist nicotine, the low-efficacy α4β2* subtype-selective agonist varenicline and the high-efficacy α7 subtype-selective agonist, PNU-282987 significantly improved DMS performance in both cocaine-naive and cocaine-experienced monkeys. Individual doses of nicotine and varenicline that engendered maximum cognitive enhancing effects on working memory did not affect discrimination or reversal learning, while PNU-282987 disrupted reversal learning in the cocaine-naive monkeys. These findings indicate that a cocaine self-administration history influenced nAChR distribution and the effects of nAChR agonists on cognitive performance, including a reduced sensitivity to the disrupting effects on reversal learning. The cognitive enhancing effects of nAChR agonists may be beneficial in combination with behavioral treatments for

  3. Effect of input multiplicity on the establishment of simian virus 40 persistent infections in rhesus monkey kidney cells.

    PubMed

    Norkin, L C

    1977-12-01

    Monolayer cultures of LLC-MK2 rhesus monkey kidney cells become persistently infected with simian virus 40 after infection at input multiplicities of 100, 10, or 1 plaque-forming unit per cell. After 3 weeks, all cells of the cultures infected at a multiplicity of 1 plaque-forming unit per cell produced the simian virus 40 T antigen. In contrast, 8 to 11 weeks elapsed before all the cells in the cultures infected at a multiplicity of 100 plaque-forming units per cell produced T antigen. Defective interfering particles and interferon production were not evident during this time.

  4. Innovative coconut-opening in a semi free-ranging rhesus monkey (Macaca mulatta): A case report on behavioral propensities

    PubMed Central

    Comins, Jordan A.; Russ, Brian E.; Humbert, Kelley A.; Hauser, Marc D.

    2012-01-01

    The present case report provides a description of the emergence of an innovative, highly beneficial for- aging behavior in a single rhesus monkey (Macaca mulatta) on the island of Cayo Santiago, Puerto Rico. Selectively choosing the island’s cement dock and nearby surrounding rocky terrain, our focal subject (ID: 84 J) opens coconuts using two types of underhand tosses: (1) a rolling motion to move it, and (2) a throwing motion up in the air to crack the shell. We discuss this innovative behavior in light of species-specific behavioral propensities. PMID:23280047

  5. Integrative proteomic analysis of the nucleus accumbens in rhesus monkeys following cocaine self-administration.

    PubMed

    Tannu, N S; Howell, L L; Hemby, S E

    2010-02-01

    The reinforcing effects and long-term consequences of cocaine self-administration have been associated with brain regions of the mesolimbic dopamine pathway, namely the nucleus accumbens (NAc). Studies of cocaine-induced biochemical adaptations in rodent models have advanced our knowledge; however, unbiased detailed assessments of intracellular alterations in the primate brain are scarce, yet essential, to develop a comprehensive understanding of cocaine addiction. To this end, two-dimensional difference in gel electrophoresis (2D-DIGE) was used to compare changes in cytosolic protein abundance in the NAc between rhesus monkeys self-administering cocaine and controls. Following image normalization, spots with significantly differential image intensities (P<0.05) were identified, excised, trypsin digested and analyzed by matrix-assisted laser-desorption ionization time-of-flight time-of-flight (MALDI-TOF-TOF). In total, 1098 spots were subjected to statistical analysis with 22 spots found to be differentially abundant of which 18 proteins were positively identified by mass spectrometry. In addition, approximately 1000 protein spots were constitutively expressed of which 21 proteins were positively identified by mass spectrometry. Increased levels of proteins in the cocaine-exposed monkeys include glial fibrillary acidic protein, syntaxin-binding protein 3, protein kinase C isoform, adenylate kinase isoenzyme 5 and mitochondrial-related proteins, whereas decreased levels of proteins included beta-soluble N-ethylmaleimide-sensitive factor attachment protein and neural and non-neural enolase. Using a complimentary proteomics approach, the differential expression of phosphorylated proteins in the cytosolic fraction of these subjects was examined. Two-dimensional gel electrophoresis (2DGE) was followed by gel staining with Pro-Q Diamond phosphoprotein gel stain, enabling differentiation of approximately 150 phosphoprotein spots between the groups. Following excision and

  6. Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane in rhesus monkeys.

    PubMed

    Li, Jun-Xu; Rice, Kenner C; France, Charles P

    2008-02-01

    Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and related drugs have been studied extensively in rodents, although the generality of those findings across species is not known. The goals of this study were to see whether monkeys could discriminate DOM and to characterize the DOM discriminative stimulus by studying a variety of drugs, including those with hallucinogenic activity in humans. Four rhesus monkeys discriminated between 0.32 mg/kg s.c. DOM and vehicle after an average of 116 (range = 85-166) sessions while responding under a fixed ratio 5 schedule of stimulus shock termination. Increasing doses of DOM occasioned increased responding on the drug lever with the training dose occasioning DOM-lever responding for up to 2 h. The serotonin (5-HT)(2A/2C) receptor antagonists ritanserin and ketanserin, the 5-HT(2A) receptor antagonist (+)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol] (MDL100907), and its (-)stereoisomer MDL100009 [(-)2,3-dimethoxyphenyl-1-[2-(4-piperidine)-methanol], but not haloperidol, completely blocked the discriminative stimulus effects of DOM. Quipazine as well as several drugs with hallucinogenic activity in humans, including (+)lysergic acid diethylamide, (-)DOM, and 2,5-dimethoxy-4-(n)-propylthiophenethylamine (2C-T-7), occasioned DOM-lever responding. The kappa-opioid receptor agonists U-50488 and salvinorin A (a hallucinogen) did not exert DOM-like effects and neither did ketamine, phencyclidine, amphetamine, methamphetamine, cocaine, morphine, yohimbine, fenfluramine, 8-hydroxy-2-(dipropylamino)tetralin hydrobromide (8-OH-DPAT), or (+/-)-2-(N-phenethyl-N-1'-propyl)amino-5-hydroxytetralin hydrochloride (N-0434). These data confirm in nonhuman primates a prominent role for 5-HT(2A) receptors in the discriminative stimulus effects of some drugs with hallucinogenic activity in humans. The failure of another drug with hallucinogenic activity (salvinorin A) to substitute for DOM indicates that

  7. Training and characterization of a quinine taste discrimination in rhesus monkeys.

    PubMed

    Aspen, J; Gatch, M B; Woods, J H

    1999-01-01

    There is a limited amount of information available about taste as a discriminative stimulus in non-human primates. The objective of this study was to establish a bitter taste (quinine sulfate) as a cue for lever selection and food reward in rhesus monkeys. Training took place in a series of steps that culminated in a schedule in which five lip contacts on a spout produced either quinine solution or water, followed by an opportunity to earn a food pellet by completing 20 presses on one of two levers. Responses on one of the levers resulted in food delivery if the solution contained quinine; responses on the other lever resulted in food delivery if the solution was water. A single session consisted of 100 randomly ordered taste trials with a 60-s interval between each trial. All of the animals acquired the discrimination, and the lowest quinine concentration that maintained consistent behavior was 0.3 mg/ml. To assess the specificity of the discrimination, compounds from other human taste categories were tested. A series of compounds that are detected as "bitter" by humans (caffeine, 1.5x10(-3) M; strychnine, 9x10(-4) M; PTC, 6x10(-5) M, denatonium benzoate, 2.24x10(-4) M; and urea, 3.0x10(-1) M) produced full generalization to the quinine sulfate discriminative stimulus, while "sweet" (sucrose, 2.9x10(-2) M) and "salty" (sodium chloride, 1.4 M) stimuli did not. There was individual variation among animals in response to "sour" compounds; acetic acid did not generalize to quinine, but HCl acid produced full generalization in one of three animals. These results suggest that a "bitter" taste cue is controlling the quinine discrimination.

  8. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

    PubMed

    Warren, Travis K; Jordan, Robert; Lo, Michael K; Ray, Adrian S; Mackman, Richard L; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S; Van Tongeren, Sean A; Garza, Nicole L; Donnelly, Ginger; Shurtleff, Amy C; Retterer, Cary J; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P; Grimes, Elizabeth; Welch, Lisa S; Gomba, Laura; Wilhelmsen, Catherine L; Nichols, Donald K; Nuss, Jonathan E; Nagle, Elyse R; Kugelman, Jeffrey R; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M; Trancheva, Iva; Feng, Joy Y; Barauskas, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R; Flint, Mike; McMullan, Laura K; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L; Spiropoulou, Christina F; Lee, William A; Nichol, Stuart T; Cihlar, Tomas; Bavari, Sina

    2016-03-17

    The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

  9. 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. PMID:26882419

  10. Diversity of Glutamatergic Synaptic Strength in Lateral Prefrontal versus Primary Visual Cortices in the Rhesus Monkey

    PubMed Central

    Luebke, Jennifer I.

    2015-01-01

    Understanding commonalities and differences in glutamatergic synaptic signaling is essential for understanding cortical functional diversity, especially in the highly complex primate brain. Previously, we have shown that spontaneous EPSCs differed markedly in layer 3 pyramidal neurons of two specialized cortical areas in the rhesus monkey, the high-order lateral prefrontal cortex (LPFC) and the primary visual cortex (V1). Here, we used patch-clamp recordings and confocal and electron microscopy to determine whether these distinct synaptic responses are due to differences in firing rates of presynaptic neurons and/or in the features of presynaptic or postsynaptic entities. As with spontaneous EPSCs, TTX-insensitive (action potential-independent) miniature EPSCs exhibited significantly higher frequency, greater amplitude, and slower kinetics in LPFC compared with V1 neurons. Consistent with these physiological differences, LPFC neurons possessed higher densities of spines, and the mean width of large spines was greater compared with those on V1 neurons. Axospinous synapses in layers 2–3 of LPFC had larger postsynaptic density surface areas and a higher proportion of large perforated synapses compared with V1. Axonal boutons in LPFC were also larger in volume and contained ∼1.6× more vesicles than did those in V1. Further, LPFC had a higher density of AMPA GluR2 receptor labeling than V1. The properties of spines and synaptic currents of individual layer 3 pyramidal neurons measured here were significantly correlated, consistent with the idea that significantly more frequent and larger synaptic currents are likely due to more numerous, larger, and more powerful synapses in LPFC compared with V1. PMID:25568107

  11. Dopaminergic Dysregulation in Prefrontal Cortex of Rhesus Monkeys Following Cocaine Self-Administration

    PubMed Central

    McIntosh, Scot; Howell, Leonard; Hemby, Scott E.

    2013-01-01

    Chronic cocaine administration regulates the expression of several proteins related to dopaminergic signaling and synaptic function in the mesocorticolimbic pathway, including the prefrontal cortex. Functional abnormalities in the prefrontal cortex are hypothesized to be due in part to the expression of proteins involved in dopamine signaling and plasticity. Adult male rhesus monkeys self-administered cocaine (i.v.) under limited (n = 4) and extended access conditions (n = 6). The abundance of surrogate markers of dopamine signaling and plasticity in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) were examined: glycosylated and non-glycosylated forms of the dopamine transporter (efficiency of dopamine transport), tyrosine hydroxylase (TH; marker of dopamine synthesis) and phosphorylated TH at Serine 30 and 40 (markers of enzyme activity), extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK 2), and phosphorylated ERK1 and ERK2 (phosphorylates TH Serine 31; markers of synaptic plasticity), and markers of synaptic integrity, spinophilin and post-synaptic density protein 95 (roles in dopamine signaling and response to cocaine). Extended cocaine access increased non-glycosylated and glycosylated DAT in DLPFC and OFC. While no differences in TH expression were observed between groups for any of the regions, extended access induced significant elevations in pTHSer31 in all regions. In addition, a slight but significant reduction in phosphorylated pTHSer40 was found in the DLPFC. Phosphorylated ERK2 was increased in all regions; however, pERK1 was decreased in ACC and OFC but increased in DLPFC. PSD-95 was increased in the OFC but not in DLPFC or ACC. Furthermore, extended cocaine self-administration elicited significant increases in spinophilin protein expression in all regions. Results from the study provide insight into the biochemical alterations occurring in primate prefrontal cortex. PMID

  12. Intrinsic connections and architectonics of posterior parietal cortex in the rhesus monkey

    SciTech Connect

    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) 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.

  13. Naltrexone effects on pituitary and gonadal hormones in male and female rhesus monkeys.

    PubMed

    Mello, N K; Mendelson, J H; Bree, M P; Skupny, A

    1988-11-01

    The long-acting opioid antagonist, naltrexone, stimulates LH and FSH in women during the early follicular phase of the menstrual cycle and is a new provocative test of hypothalamic-pituitary function (42,63). The acute effects of naltrexone (0.25, 0.50 and 1.0 mg/kg IV) on anterior pituitary (LH, FSH, PRL) and gonadal steroid (T or E2) hormones were studied in 7 female and 4 male rhesus monkeys (Macaca mulatta). Integrated plasma samples were collected at 20 min intervals for 60 min before and for 300 min after intravenous infusion of naltrexone over 10 min. In females studied during the early follicular phase (cycle days 1-3), naltrexone did not stimulate LH and significantly suppressed E2 (p less than 0.0003-0.0001) and FSH (p less than 0.006-0.0001). Naltrexone (0.50 and 1.0 mg/kg) also did not stimulate LH release in late follicular phase females (cycle days 10-12) when estradiol levels were in the peri-ovulatory range. FSH and E2 were significantly suppressed (p less than 0.01-0.05) after 1.0 mg/kg naltrexone, but not after 0.5 mg/kg naltrexone. However, in males all doses of naltrexone significantly stimulated LH (p less than 0.003-0.0001) and T (p less than 0.001-0.0001) but not FSH. LH increased significantly above baseline within 20 to 40 min and T increased significantly within 60 min. These gender differences in naltrexone's effects on pituitary gonadotropins and gonadal steroid hormones were unanticipated. These data are not concordant with clinical studies which report significant naltrexone stimulation of LH in men and in women during the early follicular phase.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3150786

  14. Multilineage differentiation of rhesus monkey embryonic stem cells in three-dimensional culture systems.

    PubMed

    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. PMID:12743323

  15. 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.

  16. Depressive-like behavioral response of adult male rhesus monkeys during routine animal husbandry procedure

    PubMed Central

    Hennessy, Michael B.; McCowan, Brenda; Jiang, Jing; Capitanio, John P.

    2014-01-01

    Social isolation is a major risk factor for the development of depressive illness; yet, no practical nonhuman primate model is available for studying processes involved in this effect. In a first study, we noted that adult male rhesus monkeys housed individually indoors occasionally exhibited a hunched, depressive-like posture. Therefore, Study 2 investigated the occurrence of a hunched posture by adult males brought from outdoor social groups to indoor individual housing. We also scored two other behaviors—lying on the substrate and day time sleeping—that convey an impression of depression. During the first week of observation following individual housing, 18 of 26 adult males exhibited the hunched posture and 21 of 26 displayed at least one depressive-like behavior. Over 2 weeks, 23 of 26 males showed depressive-like behavior during a total of only 20 min observation. Further, the behavior during the first week was positively related to the level of initial response to a maternal separation procedure experienced in infancy. In Study 3, more than half of 23 adult males of a new sample displayed depressive-like behavior during 10 min of observation each of Weeks 7–14 of individual housing. The surprisingly high frequency of depressive-like behavior in Studies 2 and 3 may have been due to recording behavior via camera with no human in the room to elicit competing responses. These results suggest that a common animal husbandry procedure might provide a practical means for examining effects of social isolation on depression-related endpoints in a nonhuman primate. The findings also suggest that trait-like differences in emotional responsiveness during separation in infancy may predict differences in responsiveness during social isolation in adulthood. PMID:25249954

  17. Dopaminergic dysregulation in prefrontal cortex of rhesus monkeys following cocaine self-administration.

    PubMed

    McIntosh, Scot; Howell, Leonard; Hemby, Scott E

    2013-01-01

    Chronic cocaine administration regulates the expression of several proteins related to dopaminergic signaling and synaptic function in the mesocorticolimbic pathway, including the prefrontal cortex. Functional abnormalities in the prefrontal cortex are hypothesized to be due in part to the expression of proteins involved in dopamine signaling and plasticity. Adult male rhesus monkeys self-administered cocaine (i.v.) under limited (n = 4) and extended access conditions (n = 6). The abundance of surrogate markers of dopamine signaling and plasticity in the dorsolateral prefrontal cortex (DLPFC), orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC) were examined: glycosylated and non-glycosylated forms of the dopamine transporter (efficiency of dopamine transport), tyrosine hydroxylase (TH; marker of dopamine synthesis) and phosphorylated TH at Serine 30 and 40 (markers of enzyme activity), extracellular signal-regulated kinase 1 and 2 (ERK1 and ERK 2), and phosphorylated ERK1 and ERK2 (phosphorylates TH Serine 31; markers of synaptic plasticity), and markers of synaptic integrity, spinophilin and post-synaptic density protein 95 (roles in dopamine signaling and response to cocaine). Extended cocaine access increased non-glycosylated and glycosylated DAT in DLPFC and OFC. While no differences in TH expression were observed between groups for any of the regions, extended access induced significant elevations in pTH(Ser31) in all regions. In addition, a slight but significant reduction in phosphorylated pTH(Ser40) was found in the DLPFC. Phosphorylated ERK2 was increased in all regions; however, pERK1 was decreased in ACC and OFC but increased in DLPFC. PSD-95 was increased in the OFC but not in DLPFC or ACC. Furthermore, extended cocaine self-administration elicited significant increases in spinophilin protein expression in all regions. Results from the study provide insight into the biochemical alterations occurring in primate prefrontal cortex

  18. Association fiber pathways to the frontal cortex from the superior temporal region in the rhesus monkey

    SciTech Connect

    Petrides, M.; Pandya, D.N.

    1988-07-01

    The projections to the frontal cortex that originate from the various areas of the superior temporal region of the rhesus monkey were investigated with the autoradiographic technique. The results demonstrated that the rostral part of the superior temporal gyrus (areas Pro, Ts1, and Ts2) projects to the proisocortical areas of the orbital and medial frontal cortex, as well as to the nearby orbital areas 13, 12, and 11, and to medial areas 9, 10, and 14. These fibers travel to the frontal lobe as part of the uncinate fascicle. The middle part of the superior temporal gyrus (areas Ts3 and paAlt) projects predominantly to the lateral frontal cortex (areas 12, upper 46, and 9) and to the dorsal aspect of the medial frontal lobe (areas 9 and 10). Only a small number of these fibers terminated within the orbitofrontal cortex. The temporofrontal fibers originating from the middle part of the superior temporal gyrus occupy the lower portion of the extreme capsule and lie just dorsal to the fibers of the uncinate fascicle. The posterior part of the superior temporal gyrus projects to the lateral frontal cortex (area 46, dorsal area 8, and the rostralmost part of dorsal area 6). Some of the fibers from the posterior superior temporal gyrus run initially through the extreme capsule and then cross the claustrum as they ascend to enter the external capsule before continuing their course to the frontal lobe. A larger group of fibers curves round the caudalmost Sylvian fissure and travels to the frontal cortex occupying a position just above and medial to the upper branch of the circular sulcus. This latter pathway constitutes a part of the classically described arcuate fasciculus.

  19. Social status modifies estradiol activation of sociosexual behavior in female rhesus monkeys

    PubMed Central

    Reding, Katherine; Michopoulos, Vasiliki; Wallen, Kim; Sanchez, Mar; Wilson, Mark E; Toufexis, Donna

    2014-01-01

    Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions. PMID:23046624

  20. Rhesus monkeys and baboons develop FVIII inhibitors in response to porcine endothelial cells or islets

    PubMed Central

    Stewart, JM; Tarantal, AF; Hawthorne, WJ; Salvaris, EJ; O’Connell, PJ; Nottle, MB; d’Apice, AJF; Cowan, PJ; Kearns-Jonker, M

    2014-01-01

    Background Xenotransplantation of porcine organs holds promise of solving the human organ donor shortage. The use of α-1,3-galactosyltransferase knockout (GTKO) pig donors mitigates hyperacute rejection, while delayed rejection is currently precipitated by potent immune and hemostatic complications. Previous analysis by our laboratory suggests FVIII inhibitors might be elicited by the structurally restricted xenoantibody response which occurs after transplantation of either pig GTKO/hCD55/hCD59/hHT transgenic neonatal islet cell clusters or GTKO endothelial cells. Methods A recombinant xenoantibody was generated using sequences from baboons demonstrating an active xenoantibody response at day 28 after GTKO/hCD55/hCD59/hHT transgenic pig neonatal islet cell cluster transplantation. Rhesus monkeys were immunized with GTKO pig endothelial cells to stimulate an anti-nonGal xenoantibody response. Serum was collected at day 0 and 7 after immunization. A two stage chromogenic assay was used to measure FVIII cofactor activity and identify antibodies which inhibit FVIII function. Molecular modeling and molecular dynamics simulations were used to predict antibody structure and the residues which contribute to antibody-FVIII interactions. Competition ELISA was used to verify predictions at the domain structural level. Results Antibodies which inhibit recombinant human FVIII function are elicited after non-human primates are transplanted with either GTKO pig neonatal islet cell clusters or endothelial cells. There is an apparent increase of inhibitor titer by 15 Bethesda units after transplant; where an increase greater than 5 Bu can indicate pathology in humans. Furthermore, competition ELISA verifies the computer modeled prediction that the recombinant xenoantibody, H66K12, binds the C1 domain of FVIII. Conclusions The development of FVIII inhibitors is a novel illustration of the potential impact the humoral immune response can have on coagulative dysfunction in

  1. Spaceflight effects on single skeletal muscle fiber function in the rhesus monkey

    NASA Technical Reports Server (NTRS)

    Fitts, R. H.; Desplanches, D.; Romatowski, J. G.; Widrick, J. J.

    2000-01-01

    The purpose of this investigation was to understand how 14 days of weightlessness alters the cellular properties of individual slow- and fast-twitch muscle fibers in the rhesus monkey. The diameter of the soleus (Sol) type I, medial gastrocnemius (MG) type I, and MG type II fibers from the vivarium controls averaged 60 +/- 1, 46 +/- 2, and 59 +/- 2 microm, respectively. Both a control 1-G capsule sit (CS) and spaceflight (SF) significantly reduced the Sol type I fiber diameter (20 and 13%, respectively) and peak force, with the latter declining from 0.48 +/- 0.01 to 0.31 +/- 0.02 (CS group) and 0.32 +/- 0.01 mN (SF group). When the peak force was expressed as kiloNewtons per square meter (kN/m(2)), only the SF group showed a significant decline. This group also showed a significant 15% drop in peak fiber stiffness that suggests that fewer cross bridges were contracting in parallel. In the MG, SF but not CS depressed the type I fiber diameter and force. Additionally, SF significantly depressed absolute (mN) and relative (kN/m(2)) force in the fast-twitch MG fibers by 30% and 28%, respectively. The Ca(2+) sensitivity of the type I fiber (Sol and MG) was significantly reduced by growth but unaltered by SF. Flight had no significant effect on the mean maximal fiber shortening velocity in any fiber type or muscle. The post-SF Sol type I fibers showed a reduced peak power and, at peak power, an elevated velocity and decreased force. In conclusion, CS and SF caused atrophy and a reduced force and power in the Sol type I fiber. However, only SF elicited atrophy and reduced force (mN) in the MG type I fiber and a decline in relative force (kN/m(2)) in the Sol type I and MG type II fibers.

  2. Noninvasive markers of bone metabolism in the rhesus monkey: normal effects of age and gender

    NASA Technical Reports Server (NTRS)

    Cahoon, S.; Boden, S. D.; Gould, K. G.; Vailas, A. C.

    1996-01-01

    Measurement of bone turnover in conditions such as osteoporosis has been limited by the need for invasive iliac bone biopsy to reliably determine parameters of bone metabolism. Recent advances in the area of serum and urinary markers of bone metabolism have raised the possibility for noninvasive measurements; however, little nonhuman primate data exist for these parameters. The purpose of this experiment was to define the normal range and variability of several of the newer noninvasive bone markers which are currently under investigation in humans. The primary intent was to determine age and gender variability, as well as provide some normative data for future experiments in nonhuman primates. Twenty-four rhesus macaques were divided into equal groups of male and female according to the following age groupings: 3 years, 5-10 years, 15-20 years, and > 25 years. Urine was collected three times daily for a four-day period and measured for several markers of bone turnoverm including pyridinoline (PYD), deoxypyrodinoline (DPD), hydroxyproline, and creatinine. Bone mineral density measurements of the lumbar spine were performed at the beginning and end of the study period. Serum was also obtained at the time of bone densitometry for measurement of osteocalcin levels by radioimmunoassay. There were no significant differences in bone mineral density, urine PYD, or urine DPD based on gender. Bone density was lowest in the youngest animals, peaked in the 15-20-year group, but again decreased in the oldest animals. The osteocalcin, PYD, and DPD levels followed an inversely related pattern to bone density. The most important result was the relative age insensitivity of the ratio of PYD:DPD in monkeys up to age 20 years. Since bone density changes take months or years to become measurable and iliac biopsies are invasive, the PYD/DPD marker ratio may have important implications for rapid noninvasive measurement of the effects of potential treatments for osteoporosis in the non

  3. Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

    PubMed

    Warren, Travis K; Jordan, Robert; Lo, Michael K; Ray, Adrian S; Mackman, Richard L; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S; Van Tongeren, Sean A; Garza, Nicole L; Donnelly, Ginger; Shurtleff, Amy C; Retterer, Cary J; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P; Grimes, Elizabeth; Welch, Lisa S; Gomba, Laura; Wilhelmsen, Catherine L; Nichols, Donald K; Nuss, Jonathan E; Nagle, Elyse R; Kugelman, Jeffrey R; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M; Trancheva, Iva; Feng, Joy Y; Barauskas, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R; Flint, Mike; McMullan, Laura K; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L; Spiropoulou, Christina F; Lee, William A; Nichol, Stuart T; Cihlar, Tomas; Bavari, Sina

    2016-03-17

    The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

  4. 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.

  5. JWH-018 in rhesus monkeys: differential antagonism of discriminative stimulus, rate-decreasing, and hypothermic effects

    PubMed Central

    Rodriguez, Jesse S.; McMahon, Lance R.

    2014-01-01

    SUMMARY Several effects of the abused synthetic cannabinoid JWH-018 were compared to those of Δ9-tetrahydrocannabinol (Δ9-THC) in rhesus monkeys. JWH-018 (0.1 mg/kg i.v.) was established as a discriminative stimulus and rimonabant was used to examine mechanisms responsible for discrimination as well as operant response rate-decreasing and hypothermic effects. JWH-018 dose-dependently increased drug-lever responding (ED50 = 0.01 mg/kg) and decreased response rate (ED50 = 0.064 mg/kg). Among various cannabinoids, the relative potency for producing discriminative stimulus and rate-decreasing effects was the same: CP-55940 = JWH-018 > Δ9-THC = WIN-55212-2 = JWH-073. The benzodiazepine agonist midazolam and the NMDA antagonist ketamine did not exert JWH-018 like discriminative stimulus effects up to doses that disrupted responding. JWH-018 and 9-THC decreased rectal temperature by 2.2 and 2.8 °C, respectively; the doses decreasing temperature by 2 °C were 0.21 and 1.14 mg/kg, respectively. Antagonism did not differ between JWH-018 and 9-THC, but did differ among effects. The apparent affinities of rimonabant calculated in the presence of JWH-018 and Δ9-THC were not different from each other for antagonism of discriminative stimulus effects (6.58 and 6.59, respectively) or hypothermic effects (7.08 and 7.19, respectively). Apparent affinity estimates are consistent with the same receptors mediating the discriminative stimulus and hypothermic effects of both JWH-018 and Δ9-THC. However, there was more limited and less orderly antagonism of rate-decreasing effects, suggesting that an additional receptor mechanism is involved in mediating the effects of cannabinoid on response rate. Overall, these results strongly suggest that JWH-018 and Δ9-THC act at the same receptors to produce several of their shared psychopharmacological effects. PMID:24972243

  6. JWH-018 in rhesus monkeys: differential antagonism of discriminative stimulus, rate-decreasing, and hypothermic effects.

    PubMed

    Rodriguez, Jesse S; McMahon, Lance R

    2014-10-01

    Several effects of the abused synthetic cannabinoid JWH-018 were compared to those of Δ9-tetrahydrocannabinol (Δ9-THC) in rhesus monkeys. JWH-018 (0.1 mg/kg i.v.) was established as a discriminative stimulus and rimonabant was used to examine mechanisms responsible for discrimination as well as operant response rate-decreasing and hypothermic effects. JWH-018 dose-dependently increased drug-lever responding (ED50=0.01 mg/kg) and decreased response rate (ED50=0.064 mg/kg). Among various cannabinoids, the relative potency for producing discriminative stimulus and rate-decreasing effects was the same: CP-55940=JWH-018>Δ9-THC=WIN-55212-2=JWH-073. The benzodiazepine agonist midazolam and the NMDA antagonist ketamine did not exert JWH-018 like discriminative stimulus effects up to doses that disrupted responding. JWH-018 and Δ9-THC decreased rectal temperature by 2.2 and 2.8°C, respectively; the doses decreasing temperature by 2°C were 0.21 and 1.14 mg/kg, respectively. Antagonism did not differ between JWH-018 and Δ9-THC, but did differ among effects. The apparent affinities of rimonabant calculated in the presence of JWH-018 and Δ9-THC were not different from each other for antagonism of discriminative stimulus effects (6.58 and 6.59, respectively) or hypothermic effects (7.08 and 7.19, respectively). Apparent affinity estimates are consistent with the same receptors mediating the discriminative stimulus and hypothermic effects of both JWH-018 and Δ9-THC. However, there was more limited and less orderly antagonism of rate-decreasing effects, suggesting that an additional receptor mechanism is involved in mediating the effects of cannabinoids on response rate. Overall, these results strongly suggest that JWH-018 and Δ9-THC act at the same receptors to produce several of their shared psychopharmacological effects.

  7. Actigraphy-Based Sleep Parameters During the Reinstatement of Methamphetamine Self-Administration in Rhesus Monkeys

    PubMed Central

    Berro, Laís F.; Andersen, Monica L.; Tufik, Sergio; Howell, Leonard L.

    2016-01-01

    The objective of the present 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. non-contingent 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, sleep-like 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 sleep-like measures. Our data indicate that the reintroduction of the stimulus light as a drug-paired cue increased nighttime activity. PMID:26882419

  8. 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

  9. Primacy and recency effects in rhesus monkeys (Macaca mulatta) using a serial probe recognition task: II. Effects of atropine sulfate.

    PubMed

    Castro, C A

    1997-08-01

    Nonhuman primates display both a primacy and a recency effect when trained on a 6-item serial probe recognition task. The author has previously shown that in the rhesus monkey, diazepam (3.2 mg/kg im) interferes with the memory processes that mediate the recency effect without affecting those memory processes involved in the primacy effect (C. A. Castro, 1995). This study assessed the effects of atropine sulfate (0.2, 0.3, and 0.4 mg/kg im) on the primacy and recency effects in these same monkeys. Opposite the effects of diazepam, atropine disrupted the primacy component of the serial position curve and had no measurable effect on the recency component. In addition, the 2 highest doses of atropine disrupted accuracy on the nonmatching probe trials, whereas all 3 doses of atropine resulted in increased response latencies. These reports indicate that the primacy and recency effects in the nonhuman primate can be pharmacologically dissociated.

  10. 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.

  11. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey

    PubMed Central

    Ngwenya, Laura B.; Heyworth, Nadine C.; Shwe, Yamin; Moore, Tara L.; Rosene, Douglas L.

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  12. Age-related changes in dentate gyrus cell numbers, neurogenesis, and associations with cognitive impairments in the rhesus monkey.

    PubMed

    Ngwenya, Laura B; Heyworth, Nadine C; Shwe, Yamin; Moore, Tara L; Rosene, Douglas L

    2015-01-01

    The generation of new neurons in the adult mammalian brain is well-established for the hippocampal dentate gyrus (DG). However, the role of neurogenesis in hippocampal function and cognition, how it changes in aging, and the mechanisms underlying this are yet to be elucidated in the monkey brain. To address this, we investigated adult neurogenesis in the DG of 42 rhesus monkeys (39 cognitively tested) ranging in age from young adult to the elderly. We report here that there is an age-related decline in proliferation and a delayed development of adult neuronal phenotype. Additionally, we show that many of the new neurons survive throughout the lifetime of the animal and may contribute to a modest increase in total neuron number in the granule cell layer of the DG over the adult life span. Lastly, we find that measures of decreased adult neurogenesis are only modestly predictive of age-related cognitive impairment. PMID:26236203

  13. 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.

  14. Induction of reciprocal translocations in rhesus monkey stem-cell spermatogonia: effects of low doses and low dose rates

    SciTech Connect

    van Buul, P.P.; Richardson, J.F. Jr.; Goudzwaard, J.H.

    1986-01-01

    The induction of reciprocal translocation in rhesus monkey spermatogonial stem cells was studied following exposure to low doses of acute X rays (0.25 Gy, 300 mGy/min) or to low-dose-rate X rays (1 Gy, 2 mGy/min) and gamma rays (1 Gy, 0.2 mGy/min). The results obtained at 0.25 Gy of X rays fitted exactly the linear extrapolation down from the 0.5 and 1.0 Gy points obtained earlier. Extension of X-ray exposure reduced the yield of translocations similar to that in the mouse by about 50%. The reduction to 40% of translocation rate after chronic gamma exposure was clearly less than the value of about 80% reported for the mouse over the same range of dose rates. Differential cell killing with ensuing differential elimination of aberration-carrying cells is the most likely explanation for the differences between mouse and monkey.

  15. 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

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

    PubMed Central

    Hara, Yuko; Yuk, Frank; Puri, Rishi; Janssen, William G. M.; Rapp, Peter R.

    2016-01-01

    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

  17. Effects of cocaine and corticotropin-releasing factor on pulsatile ACTH and cortisol release in ovariectomized rhesus monkeys.

    PubMed

    Sarnyai, Z; Mello, N K; Mendelson, J H; Nguyen, P H; Erös-Sarnyai, M

    1995-09-01

    Cocaine stimulates ACTH secretion by a corticotropin-releasing factor (CRF)-dependent mechanism in male rats, rhesus monkeys, and humans. To determine the generality of this effect, we examined the effects of acute cocaine administration on the pulsatile release of ACTH and cortisol in three ovariectomized (OVX) rhesus monkeys and compared its effects to stimulation with CRF. Venous blood samples were collected at 2-min intervals for 60 min before and after iv administration of cocaine (0.4 and 0.8 mg/kg) and CRF (1.0 and 10 micrograms/kg). Cluster analysis procedures were used to evaluate the pulsatile characteristics of ACTH and cortisol release. After placebo administration, an ACTH pulse frequency of 3 peaks/h was detected. After cocaine administration, plasma cocaine levels peaked at 92 +/- 3.0 and 201 +/- 60 ng/mL within 2 min. However, in contrast to normal intact males, cocaine did not stimulate the pulsatile release of ACTH in OVX females. Cocaine (0.4 mg/kg) decreased ACTH incremental peak height and valley levels compared with pre-cocaine values, and a higher dose of cocaine produced no changes in ACTH release. Bolus injection of a low dose of CRF (1.0 micrograms/kg, iv) significantly increased ACTH incremental peak height (P < 0.05), and a higher dose of CRF (10 micrograms/kg) increased ACTH peak amplitude, percentage increase in peak amplitude, area under the peaks, and incremental peak heights as well as ACTH valley level and nadir (10 micrograms/kg, iv) (P < 0.05). ACTH pulse frequency did not change after CRF or cocaine administration. Pulsatile release of cortisol was 2.7 peaks/h under placebo conditions and did not change after cocaine or CRF administration. Cortisol pulse amplitude was increased after low and high doses of CRF. High doses of CRF (10 micrograms/kg) also increased the mean level of cortisol valleys. In summary, we found that CRF but not cocaine stimulated pulsatile ACTH and cortisol release in OVX rhesus monkeys. The profound ACTH

  18. Characterization of the Discriminative Stimulus Effects of a NOP Receptor Agonist Ro 64-6198 in Rhesus Monkeys.

    PubMed

    Saccone, Phillip A; Zelenock, Kathy A; Lindsey, Angela M; Sulima, Agnieszka; Rice, Kenner C; Prinssen, Eric P; Wichmann, Jürgen; Woods, James H

    2016-04-01

    Nociceptin/orphanin FQ receptor (NOP) agonists have been reported to produce antinociceptive effects in rhesus monkeys with comparable efficacy to μ-opioid receptor (MOP) agonists, but without their limiting side effects. There are also known to be species differences between rodents and nonhuman primates (NHPs) in the behavioral effects of NOP agonists. The aims of this study were the following: 1) to determine if the NOP agonist Ro 64-6198 could be trained as a discriminative stimulus; 2) to evaluate its pharmacological selectivity as a discriminative stimulus; and 3) to establish the order of potency with which Ro 64-6198 produces discriminative stimulus effects compared with analgesic effects in NHPs. Two groups of rhesus monkeys were trained to discriminate either fentanyl or Ro 64-6198 from vehicle. Four monkeys were trained in the warm-water tail-withdrawal procedure to measure antinociception. Ro 64-6198 produced discriminative stimulus effects that were blocked by the NOP antagonist J-113397 and not by naltrexone. The discriminative stimulus effects of Ro 64-6198 partially generalized to diazepam, but not to fentanyl, SNC 80, ketocyclazocine, buprenorphine, phencyclidine, or chlorpromazine. Fentanyl produced stimulus effects that were blocked by naltrexone and not by J-113397, and Ro 64-6198 did not produce fentanyl-appropriate responding in fentanyl-trained animals. In measures of antinociception, fentanyl, but not Ro 64-6198, produced dose-dependent increases in tail-withdrawal latency. Together, these results demonstrate that Ro 64-6198 produced stimulus effects in monkeys that are distinct from other opioid receptor agonists, but may be somewhat similar to diazepam. In contrast to previous findings, Ro 64-6198 did not produce antinociception in the majority of animals tested even at doses considerably greater than those that produced discriminative stimulus effects. PMID:26801398

  19. Characterization of the Discriminative Stimulus Effects of a NOP Receptor Agonist Ro 64-6198 in Rhesus Monkeys

    PubMed Central

    Zelenock, Kathy A.; Lindsey, Angela M.; Sulima, Agnieszka; Rice, Kenner C.; Prinssen, Eric P.; Wichmann, Jürgen; Woods, James H.

    2016-01-01

    Nociceptin/orphanin FQ receptor (NOP) agonists have been reported to produce antinociceptive effects in rhesus monkeys with comparable efficacy to μ-opioid receptor (MOP) agonists, but without their limiting side effects. There are also known to be species differences between rodents and nonhuman primates (NHPs) in the behavioral effects of NOP agonists. The aims of this study were the following: 1) to determine if the NOP agonist Ro 64-6198 could be trained as a discriminative stimulus; 2) to evaluate its pharmacological selectivity as a discriminative stimulus; and 3) to establish the order of potency with which Ro 64-6198 produces discriminative stimulus effects compared with analgesic effects in NHPs. Two groups of rhesus monkeys were trained to discriminate either fentanyl or Ro 64-6198 from vehicle. Four monkeys were trained in the warm-water tail-withdrawal procedure to measure antinociception. Ro 64-6198 produced discriminative stimulus effects that were blocked by the NOP antagonist J-113397 and not by naltrexone. The discriminative stimulus effects of Ro 64-6198 partially generalized to diazepam, but not to fentanyl, SNC 80, ketocyclazocine, buprenorphine, phencyclidine, or chlorpromazine. Fentanyl produced stimulus effects that were blocked by naltrexone and not by J-113397, and Ro 64-6198 did not produce fentanyl-appropriate responding in fentanyl-trained animals. In measures of antinociception, fentanyl, but not Ro 64-6198, produced dose-dependent increases in tail-withdrawal latency. Together, these results demonstrate that Ro 64-6198 produced stimulus effects in monkeys that are distinct from other opioid receptor agonists, but may be somewhat similar to diazepam. In contrast to previous findings, Ro 64-6198 did not produce antinociception in the majority of animals tested even at doses considerably greater than those that produced discriminative stimulus effects. PMID:26801398

  20. Synaptic estrogen receptor-alpha levels in prefrontal cortex in female rhesus monkeys and their correlation with cognitive performance

    PubMed Central

    Morrison, John; Wang, Athena C.J.; Hara, Yuko; Janssen, William G.M.; Rapp, Peter R.

    2010-01-01

    In rat hippocampus, estrogen receptor-alpha (ER-α) can initiate non-genomic signaling mechanisms that modulate synaptic plasticity in response to either circulating or locally synthesized estradiol (E). Here we report quantitative electron microscopic data demonstrating that ER-α is present within excitatory synapses in dorsolateral prefrontal cortex (dlPFC) of young and aged ovariectomized female rhesus monkeys with and without E treatment. There were no treatment or age effects on the percentage of excitatory synapses containing ER-α, nor were there any group differences in distribution of ER-α within the synapse. However, the mean size of synapses containing ER-α was larger than unlabeled excitatory synapses. All monkeys were tested on delayed response (DR), a cognitive test of working memory that requires dlPFC. In young ovariectomized monkeys without E treatment, presynaptic ER-α correlated with DR accuracy across memory delays. In aged monkeys that received E treatment, ER-α within the postsynaptic density (30–60 nm from the synaptic membrane) positively correlated with DR performance. Thus, while the lack of group effects suggests that ER-α is primarily in synapses that are stable across age and treatment, synaptic abundance of ER-α is correlated with individual performance in two key age/treatment groups. These data have important implications for individual differences in the cognitive outcome among menopausal women and promote a focus on cortical estrogen receptors for therapeutic efficacy with respect to cognition. PMID:20861381

  1. Impact of early life stress on the reinforcing and behavioral-stimulant effects of psychostimulants in rhesus monkeys.

    PubMed

    Ewing Corcoran, Sarah B; Howell, Leonard L

    2010-02-01

    Early life stress has effects on behavior and stress reactivity, which are linked to enhanced sensitivity to stimulants in rodents. This study investigated whether rhesus monkeys that experienced early life stress would show altered sensitivity to the reinforcing effects of stimulants as compared with controls. Control (n=5) and maternally separated (n=4) monkeys were trained to self-administer cocaine (0.1 mg/kg/injection) under a second-order schedule of intravenous drug delivery. The rate of acquisition and subsequent dose-effect determinations for cocaine (0.01-1.0 mg/kg/injection) and amphetamine (0.003-0.3 mg/kg/injection) provided complementary measures of reinforcing effectiveness. In addition, stimulant-induced increases in home cage activity and dopamine D2 receptor binding potential were quantified with positron emission tomography neuroimaging. Compared with controls, maternally separated monkeys showed lower responding during the acquisition of self-administration and in the dose-response curves for both stimulants, and significantly lower response rates during maintenance of cocaine self-administration. Maternally separated monkeys also failed to exhibit stimulant-induced increases in motor activity. Groups did not differ in dopamine D2 receptor binding potential in the caudate nucleus or the putamen. Taken together, the results of this study do not provide support for early life stress leading to enhanced vulnerability to stimulant use in the nonhuman primate model employed. PMID:20016373

  2. Self-administration of agonists selective for dopamine D2, D3, and D4 receptors by rhesus monkeys.

    PubMed

    Koffarnus, Mikhail N; Collins, Gregory T; Rice, Kenner C; Chen, Jianyong; Woods, James H; Winger, Gail

    2012-08-01

    Dopamine receptor mechanisms are believed to play a role in the reinforcing effects of cocaine and other drugs of abuse. The lack of receptor-selective agonists has made it difficult to determine the role of the individual dopamine receptors in mediating these reinforcing effects. In this study, rhesus monkeys with a history of intravenous cocaine self-administration were tested for the reinforcing effects of several D(3)-preferring agonists, a D(2)-preferring agonist, and a D(4) agonist. The D(2)-preferring agonist did not maintain responding in any monkeys, and the D(4) agonist was self-administered at low rates, just above those maintained by saline, in one monkey. The D(3)-preferring agonists were self-administered by approximately half of the animals, although at lower rates than cocaine. These results indicate that the apparent limited reinforcing effectiveness of D(2)-like agonists requires activity at D(3) receptors. Previous data from this laboratory and others also suggest that these drugs may not serve as reinforcers directly; the behavior may be maintained by response-contingent delivery of stimuli previously paired with cocaine. The ability of drug-related stimuli to maintain responding apparently differs among monkeys and other organisms, and may be related to individual differences in drug-taking behavior in humans. PMID:22785383

  3. Individual differences in physical activity are closely associated with changes in body weight in adult female rhesus monkeys (Macaca mulatta)

    PubMed Central

    Sullivan, Elinor L.; Koegler, Frank H.; Cameron, Judy L.

    2010-01-01

    The increased prevalence of overweight adults has serious health consequences. Epidemiological studies suggest an association between low activity and being over-weight; however, few studies have objectively measured activity during a period of weight gain, so it is unknown whether low activity is a cause or consequence of being overweight. To determine whether individual differences in adult weight gain are linked to an individual's activity level, we measured activity, via accelerometry, over a prolonged period (9 mo) in 18 adult female rhesus monkeys. Weight, food intake, metabolic rate, and activity were first monitored over a 3-mo period. During this period, there was mild but significant weight gain (5.5 ± 0.88%; t =−6.3, df = 17, P < 0.0001), whereas caloric intake and activity remained stable. Metabolic rate increased, as expected, with weight gain. Activity level correlated with weight gain (r = −0.52, P = 0.04), and the most active monkeys gained less weight than the least active monkeys (t = −2.74, df = 8, P = 0.03). Moreover, there was an eightfold difference in activity between the most and least active monkeys, and initial activity of each monkey was highly correlated with their activity after 9 mo (r = 0.85, P < 0.0001). In contrast, food intake did not correlate with weight gain, and there was no difference in weight gain between monkeys with the highest vs. lowest caloric intake, total metabolic rate, or basal metabolic rate. We conclude that physical activity is a particularly important factor contributing to weight change in adulthood and that there are large, but stable, differences in physical activity among individuals. PMID:16614060

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

    SciTech Connect

    Johnson, Reed F.; Hammoud, Dima A.; Lackemeyer, Matthew G.; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E.; Jahrling, Peter B.

    2015-07-15

    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{sub 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.

  5. Outbreak of Tuberculosis in a Colony of Rhesus Monkeys (Macaca mulatta) after Possible Indirect Contact with a Human TB Patient.

    PubMed

    Mätz-Rensing, K; Hartmann, T; Wendel, G M; Frick, J S; Homolka, S; Richter, E; Munk, M H; Kaup, F-J

    2015-01-01

    Simian tuberculosis is one of the most important bacterial diseases of non-human primates. Outbreaks of tuberculosis have been reported in primate colonies almost as long as these animals have been used experimentally or kept in zoological gardens. Significant progress has been made in reducing the incidence of tuberculosis in captive non-human primates, but despite reasonable precautions, outbreaks continue to occur. The most relevant reason is the high incidence of tuberculosis (TB) amongst the human population, in which tuberculosis is regarded as an important re-emerging disease. Furthermore, many non-human primate species originate from countries with a high burden of human TB. Therefore, Mycobacterium tuberculosis remains a significant threat in animals imported from countries with high rates of human infection. We report an outbreak of tuberculosis among a group of rhesus monkeys (Macaca mulatta) living in a closed, long-term colony. The outbreak coincided with reactivation of a TB infection in a co-worker who never had direct access to the animal house or laboratories. Eleven of 26 rhesus monkeys developed classical chronic active tuberculosis with typical caseous granulomata of varying size within different organs. The main organ system involved was the lung, suggesting an aerosol route of infection. Such an outbreak has significant economic consequences due to animal loss, disruption of research and costs related to disease control. Precautionary measures must be improved in order to avoid TB in non-human primate colonies.

  6. Protection from radiation-induced damage of spermatogenesis in the rhesus monkey (Macaca mulatta) by follicle-stimulating hormone

    SciTech Connect

    van Alphen, M.M.; van de Kant, H.J.; de Rooij, D.G.

    1989-02-01

    In adult rhesus monkeys a two- to threefold increase in the number of spermatogonia was found at Day 75 after 1 Gy of X-irradiation when the animals were pretreated with two intramuscular injections of follicle-stimulating hormone (FSH) each day. Also the percentage of cross-sections of seminiferous tubules showing spermatogonia (repopulation index) was much higher when FSH was given before irradiation. At 75 days postirradiation the repopulation index was 39 +/- 10% after irradiation alone and 81 +/- 11% when FSH pretreatment was applied. The pretreatment with two injections of FSH each day during 16 days caused an increase in the number of proliferating A spermatogonia. In view of earlier results in the mouse, where proliferating spermatogonial stem cells appeared more radioresistant than quiescent ones, it is suggested that the protective effects of FSH treatment are caused by the increase in the proliferative activity of the A spermatogonia and consequently of the spermatogonial stem cells. The results indicate that in the rhesus monkey the maximal protective effect of FSH is reached after a period of treatment between 7 and 16 days.

  7. Autoradiographic localization of /sup 3/H-dihydrotestosterone in the preoptic area, hypothalamus, and amygdala of a male rhesus monkey

    SciTech Connect

    Michael, R.P.; Rees, H.D.

    1982-06-14

    In a preliminary study, autoradiography was used to localize target cells for /sup 3/H-dihydrotestosterone (DHT), a non-aromatizable androgen, in the brain of the rhesus monkey. One castrated male was injected intravenously with 2 mCi of /sup 3/H-DHT (0.42 ..mu..g/kg), and was killed one hour later. Neurons that concentrated radioactivity in their nuclei were located in widespread areas of the brain, which included the medial and suprachiasmatic preoptic nuclei, bed nucleus of the stria terminalis, lateral septal nucleus, anterior hypothalamic area, ventromedial, arcuate, dorsomedial, and paraventricular hypothalamic nuclei, ventral premammillary nucleus, and medial, cortical, basal accessory, and lateral amygdaloid nuclei. These results indicate that the topographic distribution of androgen target neurons is considerably wider than that observed in a study using /sup 3/H-testosterone (T) in the male rhesus monkey. However, further work is needed to elucidate these differences before attempting correlations between behavioral activity and androgen receptors in the brain.

  8. Discovery of Triazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys

    PubMed Central

    2015-01-01

    Hit-to-lead efforts resulted in the discovery of compound 19, a potent CYP11B2 inhibitor that displays high selectivity vs related CYPs, good pharmacokinetic properties in rat and rhesus, and lead-like physical properties. In a rhesus pharmacodynamic model, compound 19 displays robust, dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels. PMID:26288685

  9. Exposure of rhesus monkeys to cowpox virus Brighton Red by large-particle aerosol droplets results in an upper respiratory tract disease.

    PubMed

    Johnson, Reed F; Hammoud, Dima A; Perry, Donna L; Solomon, Jeffrey; Moore, Ian N; Lackemeyer, Matthew G; Bohannon, Jordan K; Sayre, Philip J; Minai, Mahnaz; Papaneri, Amy B; Hagen, Katie R; Janosko, Krisztina B; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E; Jahrling, Peter B

    2016-08-01

    We previously demonstrated that small-particle (0.5-3.0 µm) aerosol infection of rhesus monkeys (Macaca mulatta) with cowpox virus (CPXV)-Brighton Red (BR) results in fulminant respiratory tract disease characterized by severe lung parenchymal pathology but only limited systemic virus dissemination and limited classic epidermal pox-like lesion development (Johnson et al., 2015). Based on these results, and to further develop CPXV as an improved model of human smallpox, we evaluated a novel large-particle aerosol (7.0-9.0 µm) exposure of rhesus monkeys to CPXV-BR and monitored for respiratory tract disease by serial computed tomography (CT). As expected, the upper respiratory tract and large airways were the major sites of virus-induced pathology following large-particle aerosol exposure. Large-particle aerosol CPXV exposure of rhesus macaques resulted in severe upper airway and large airway pathology with limited systemic dissemination. PMID:27166137

  10. The effects of chronic methylphenidate administration on operant test battery performance in juvenile rhesus monkeys.

    PubMed

    Rodriguez, J S; Morris, S M; Hotchkiss, C E; Doerge, D R; Allen, R R; Mattison, D R; Paule, M G

    2010-01-01

    Methylphenidate (MPH) is an amphetamine derivative widely prescribed for the treatment of attention deficit-hyperactivity disorder. Recent concern over its genotoxic potential in children [11] spurred a study on the effects of chronic MPH treatment in a nonhuman primate population and the studies reported here were conducted in conjunction with that study in the same animals. Here, the focus was on the ability of juvenile rhesus monkeys to learn how to perform a battery of operant behavioral tasks while being treated chronically with MPH. Performance of the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB) was used to quantify the learning of tasks thought to model specific aspects of cognitive function including learning, motivation, color and position discrimination, and short-term memory. The OTB tasks designed to assess these specific behaviors included Incremental Repeated Acquisition (IRA), Progressive Ratio (PR), Conditioned Position Responding (CPR), and Delayed Matching-to-Sample (DMTS), respectively. Juvenile males (n=10/group) pressed levers and press-plates for banana-flavored food pellets. Subjects were treated orally, twice a day, five days per week (M-F) for 66 weeks with escalating doses (0.15 mg/kg initially, increased to 2.5 mg/kg for the low dose group and to 12.5 mg/kg for the high dose group) and tested in OTB tasks 30 to 60 min after the morning dose. The findings indicate that MPH at doses up to 2.5 mg/kg twice per day were well tolerated (performance was no different than controls) but at doses of 12.5 mg/kg twice per day there was a significant decrement in OTB performance, characterized by decreases in both percent task completed and response rates for all tasks. These effects of MPH seem primarily due to decreases in motivation to perform for food, which is not surprising given the well known appetite suppressing effects of amphetamine-like stimulants. Thus, the current data do not strongly suggest cognitive

  11. Posterior hypothalamic lesions advance the onset of puberty in the female rhesus monkey.

    PubMed

    Terasawa, E; Noonan, J J; Nass, T E; Loose, M D

    1984-12-01

    The effects of experimental lesions in the posterior hypothalamus and the anterior hypothalamus on menarche and first ovulation were examined in nonhuman primates. With the aid of x-ray ventriculography, bilateral lesions were made by passing a radiofrequency current through a thermister electrode in the posterior hypothalamus (n = 7) or the anterior hypothalamus (n = 6) of female rhesus monkeys at 18 months of age. Four animals that received sham lesions as well as four normal females of a similar age served as controls. All animals were caged individually and examined daily for vaginal bleeding and sex skin color change. Developmental changes in gonadotropins, ovarian steroids, body weight, and nipple size were monitored throughout the experiments. The time of first ovulation was determined by laparoscopic observation of the newly formed corpus luteum and by the level of circulating progesterone. Histological examination confirmed that the bilateral lesions in the hypothalamus were approximately 2-3 mm in diameter and overlapped midline. Primary sites of posterior hypothalamic lesions included the premamillary area and the posterior nucleus, while the infundibular nucleus and the median eminence were entirely spared. The posterior lesions encroached upon the mamillary nuclei caudally in most cases and upon the ventromedial nucleus rostrally in some cases. Primary sites of anterior hypothalamic lesions included the medial preoptic area, the periventricular preoptic nucleus, and the anterior hypothalamic nucleus. Partial lesions of the diagonal bundle of Broca, the medial preoptic nucleus, and the paraventricular nucleus were also detected. Posterior hypothalamic lesions advanced the ages at menarche (22.2 +/- 1.3 months; P less than 0.001) and first ovulation (40.7 +/- 2.7 months; P less than 0.05) compared to those of control animals (menarche, 30.3 +/- 3.1; first ovulation, 51.2 +/- 3.3 months). The body weight at menarche of these lesioned animals (2.62 +/- 0

  12. Synthesis and dopamine transporter imaging in rhesus monkeys with fluorine-18 labeled FECT

    SciTech Connect

    Keil, R.; Hoffman, J.M.; Eschima, D.

    1996-05-01

    Parkinson`s patients have been shown to suffer a 60-80% loss of dopamine transporters in the substantia nigra and striatum. Dopamine transporter ligands labeled with fluorine-18 (t {1/2}=110 min) are attractive probes for measuring the density of dopamine transporter sites n the striatum for the diagnosis and evaluation of Parkinson`s patients by PET. We have synthesized (Ki = 32 nM vs RTI-55), fluorine-18 labeled 2{beta}-carbomethoxy-3{beta}(4-chlorophenyl)-8-(3-fluoropropyl)nortropane (FECT), with favorable kinetics as a potential dopamine transporter PET imaging agent. Treatment of 2{beta}-carbomethoxy-3{beta}-(4-chlorophenyl)nortropane (1) with 1-bromo-2-fluoroethane (2) in CH3CN at 80{degrees}C gave FECT (3). [F-18]FECT (3) was prepared by treating 1,2-ditosyloxyethane (4) with NCA K[F-18]/K222 (365 mCi) for 5 min in CH3CN at 85{degrees}C to give [F-18] 1-fluoro-2-tosyloxyethane (5) (175 mCi)in 59% E.O.B. yield. Coupling of [F-18] 5 with 1 in DMF at 135 {degrees}C for 45 min gave [F-18]FECT (41 mCi) in 25% yield E.O.B. following HPLC purification in a total synthesis time of 122 min. [F-18] 5 was >99% radiochemically pure with a specific activity of 5 Ci/{mu}mole. Following intravenous administration to a rhesus monkey [F-18]FECT (8.13 mCi) showed a peak uptake at 30 min in the striatum (S) followed by a slow clearance and a rapid washout from the cerebellum to afford a high S/C ratio = 11.0 at 125 min. Radio-HPLC analysis of the ether extracts form plasma samples for radioactive metabolites detected only the presence of [F-18]FECT. These results suggest that FECT is an Research supported by DOE.

  13. Effects of combined dopamine and serotonin transporter inhibitors on cocaine self-administration in rhesus monkeys.

    PubMed

    Howell, Leonard L; Carroll, F Ivy; Votaw, John R; Goodman, Mark M; Kimmel, Heather L

    2007-02-01

    Dopamine transporter (DAT) inhibitors may represent a promising class of drugs in the development of cocaine pharmacotherapies. In the present study, the effects of pretreatments with the selective DAT inhibitor 3beta-(4-chlorophenyl)tropane-2beta-[3-(4'-methylphenyl)isoxazol-5-yl] hydrochloride (RTI-336) (0.3-1.7 mg/kg) were characterized in rhesus monkeys trained to self-administer cocaine (0.1 and 0.3 mg/kg/injection) under a multiple second-order schedule of i.v. drug or food delivery. In addition, RTI-336 (0.01-1.0 mg/kg/injection) was substituted for cocaine to characterize its reinforcing effects. Last, the dose of RTI-336 that reduced cocaine-maintained behavior by 50% (ED(50)) was coadministered with the selective serotonin transporter (SERT) inhibitors fluoxetine (3.0 mg/kg) and citalopram (3.0 mg/kg) to characterize their combined effects on cocaine self-administration. PET neuroimaging with the selective DAT ligand [(18)F]8-(2-[(18)F]fluoroethyl)-2beta-carbomethoxy-3beta-(4-chlorophenyl)nortropane quantified DAT occupancy at behaviorally relevant doses of RTI-336. Pretreatments of RTI-336 produced dose-related reductions in cocaine self-administration, and the ED(50) dose resulted in approximately 90% DAT occupancy. RTI-336 was reliably self-administered, but responding maintained by RTI-336 was lower than responding maintained by cocaine. Doses of RTI-336 that maintained peak rates of responding resulted in approximately 62% DAT occupancy. Co-administration of the ED(50) dose of RTI-336 in combination with either SERT inhibitor completely suppressed cocaine self-administration without affecting DAT occupancy. Hence, at comparable levels of DAT occupancy, coadministration of SERT inhibitors with RTI-336 produced more robust reductions in cocaine self-administration compared with RTI-336 alone. Collectively, the results indicate that combined inhibition of DAT and SERT warrants consideration as a viable approach in the development of cocaine medications

  14. Circadian force and EMG activity in hindlimb muscles of rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Hodgson, J. A.; Wichayanuparp, S.; Recktenwald, M. R.; Roy, R. R.; McCall, G.; Day, M. K.; Washburn, D.; Fanton, J. W.; Kozlovskaya, I.; Edgerton, V. R.; Rumbaugh, D. M. (Principal Investigator)

    2001-01-01

    Continuous intramuscular electromyograms (EMGs) were recorded from the soleus (Sol), medial gastrocnemius (MG), tibialis anterior (TA), and vastus lateralis (VL) muscles of Rhesus during normal cage activity throughout 24-h periods and also during treadmill locomotion. Daily levels of MG tendon force and EMG activity were obtained from five monkeys with partial datasets from three other animals. Activity levels correlated with the light-dark cycle with peak activities in most muscles occurring between 08:00 and 10:00. The lowest levels of activity generally occurred between 22:00 and 02:00. Daily EMG integrals ranged from 19 mV/s in one TA muscle to 3339 mV/s in one Sol muscle: average values were 1245 (Sol), 90 (MG), 65 (TA), and 209 (VL) mV/s. The average Sol EMG amplitude per 24-h period was 14 microV, compared with 246 microV for a short burst of locomotion. Mean EMG amplitudes for the Sol, MG, TA, and VL during active periods were 102, 18, 20, and 33 microV, respectively. EMG amplitudes that approximated recruitment of all fibers within a muscle occurred for 5-40 s/day in all muscles. The duration of daily activation was greatest in the Sol [151 +/- 45 (SE) min] and shortest in the TA (61 +/- 19 min). The results show that even a "postural" muscle such as the Sol was active for only approximately 9% of the day, whereas less active muscles were active for approximately 4% of the day. MG tendon forces were generally very low, consistent with the MG EMG data but occasionally reached levels close to estimates of the maximum force generating potential of the muscle. The Sol and TA activities were mutually exclusive, except at very low levels, suggesting very little coactivation of these antagonistic muscles. In contrast, the MG activity usually accompanied Sol activity suggesting that the MG was rarely used in the absence of Sol activation. The results clearly demonstrate a wide range of activation levels among muscles of the same animal as well as among different

  15. 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

  16. Bone growth in juvenile rhesus monkeys is influenced by 5HTTLPR polymorphisms and interactions between 5HTTLPR polymorphisms and fluoxetine

    PubMed Central

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

    2015-01-01

    Male rhesus monkeys received a therapeutic oral dose of the selective serotonin reuptake inhibitor (SSRI) fluoxetine daily from 1 to 3 years of age. Puberty is typically initiated between 2 and 3 years of age in male rhesus and reproductive maturity is reached at 4 years. The study group was genotyped for polymorphisms in the monoamine oxidase A (MAOA) and serotonin transporter (SERT) genes that affect serotonin neurotransmission. Growth was assessed with morphometrics at 4 month intervals and radiographs of long bones were taken at 12 month intervals to evaluate skeletal growth and maturation. No effects of fluoxetine, or MAOA or SERT genotype were found for growth during the first year of the study. Linear growth began to slow during the second year of the study and serotonin reuptake transporter (SERT) long polymorphic region (5HTTLPR) polymorphism effects with drug interactions emerged. Monkeys with two SERT 5HTTLPR L alleles (LL, putative greater transcription) had 25–39% less long bone growth, depending on the bone, than monkeys with one S and one L allele (SL). More advanced skeletal maturity was also seen in the LL group, suggesting earlier onset of puberty. An interaction between 5HTTLPR polymorphisms and fluoxetine was identified for femur and tibia growth; the 5HTTLPR effect was seen in controls (40% less growth for LL) but not in the fluoxetine treated group (10% less growth for LL). A role for serotonin in peripubertal skeletal growth and maturation has not previously been investigated but may be relevant to treatment of children with SSRIs. PMID:26067181

  17. 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.

  18. The Macaque Social Responsiveness Scale (mSRS): A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta).

    PubMed

    Feczko, Eric J; Bliss-Moreau, Eliza; Walum, Hasse; Pruett, John R; Parr, Lisa A

    2016-01-01

    Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS) is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS). Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological mechanisms underlying

  19. The Macaque Social Responsiveness Scale (mSRS): A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta).

    PubMed

    Feczko, Eric J; Bliss-Moreau, Eliza; Walum, Hasse; Pruett, John R; Parr, Lisa A

    2016-01-01

    Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS) is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS). Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological mechanisms underlying

  20. The Macaque Social Responsiveness Scale (mSRS): A Rapid Screening Tool for Assessing Variability in the Social Responsiveness of Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Bliss-Moreau, Eliza; Walum, Hasse; Pruett, John R.

    2016-01-01

    Understanding the biological mechanisms underlying human neuropsychiatric disorders, such as autism spectrum disorder (ASD), has been hindered by the lack of a robust, translational animal model. Rhesus monkeys (Macaca mulatta) display many of the same social behaviors that are affected in ASD, making them an excellent animal species in which to model social impairments. However, the social impairments associated with ASD may reflect extreme ends of a continuous distribution of traits. Thus, to validate the rhesus monkey as an animal model for studying social impairments that has strong translational relevance for ASD, researchers need an easily-implemented measurement tool that can quantify variation in social behavior dimensionally. The Social Responsiveness Scale (SRS) is a 65-item survey that identifies both typical and atypical social behaviors in humans that covary with ASD symptom severity. A chimpanzee SRS has already been validated and the current study adapted this tool for use in the rhesus monkey (mSRS). Fifteen raters completed the mSRS for 105 rhesus monkeys living at the Yerkes National Primate Research Center. The mSRS scores showed a unimodal distribution with a positive skew that identified 6 statistical outliers. Inter-rater reliability was very strong, but only 17 of the 36 questions showed positive intra-item reliability. The results of an exploratory factor analysis identified 3 factors that explained over 60% of the variance, with 12 items significantly loading onto the primary factor. These items reflected behaviors associated with social avoidance, social anxiety or inflexibility and social confidence. These initial findings are encouraging and suggest that variability in the social responsiveness of rhesus monkeys can be quantified using the mSRS: a tool that has strong translational relevance for human disorders. With further modification, the mSRS may provide an promising new direction for research on the biological mechanisms underlying

  1. Smoked heroin in rhesus monkeys: effects of heroin extinction and fluid availability on measures of heroin seeking.

    PubMed

    Evans, Suzette M; Nasser, Jennifer; Comer, Sandra D; Foltin, Richard W

    2003-02-01

    The purpose of the present study was to evaluate the reinforcing effects of smoked heroin in nonopioid-dependent nonhuman primates when an alternative reinforcer, sweetened fluid, was made available. Four adult male rhesus monkeys lived in three chambers, with heroin self-administration (0, 0.3, and 0.6 mg/kg) specific to one end of the chamber, oral sweetened fluid self-administration specific to the other end chamber, and no commodity available in the middle chamber. The length of time monkeys spent in the drug-associated chamber provided one measure of drug seeking (i.e., location preference). During self-administration sessions, a second-order schedule of reinforcement was used, with responding during the first component maintained by a brief presentation of the stimuli associated with reinforcement. Responding during the second component was maintained by a delivery of the reinforcer, and the associated stimuli. Responding during the first component provided a second measure of drug seeking. Monkeys also had choice trials each day, when they could choose to work for either commodity. Choice behavior provided a third measure of drug seeking. Each experimental day consisted of a smoking session (four smoking trials), a sweetened fluid session (four fluid trials), and a choice session (four choice trials). Monkeys typically completed all four smoking trials each day when either of the active heroin doses was available. They chose both heroin doses over fluid on 3.5 of the four choice trials, and they had a location preference for the heroin chamber. Under baseline conditions, the number of acquisition responses and the number of consumption responses (inhalations) were greater for the high dose of heroin compared to the low dose of heroin. Further, it took longer to extinguish the responding for the high dose of heroin compared to the low dose of heroin when a vehicle was substituted. During heroin extinction, acquisition responding for fluid increased, the

  2. Effects of HCFC-123 exposure to maternal and infant rhesus monkeys on hepatic biochemistry, lactational parameters and postnatal growth.

    PubMed

    Cappon, G D; Keller, D A; Brock, W J; Slauter, R W; Hurtt, M E

    2002-11-01

    Peroxisome proliferators are a class of nongenotoxic rodent hepatocarcinogens that cause peroxisome proliferation and liver tumors when administered to rats and mice; but other species, including guinea pigs, dogs, and primates are less sensitive or refractory to the induction of peroxisome proliferation. Therefore, rodent peroxisome proliferators are not believed to pose a hepatocarcinogenic hazard to humans. Some peroxisome proliferators produce developmental toxicity in rats that is expressed as suppressed postnatal growth. To evaluate the relevance of the rat developmental effect to primates, groups of 4 lactating female Rhesus monkeys and their infants were exposed for 6 h/day, 7 days/week for 3 weeks to air or 1000 ppm HCFC-123. Animals were evaluated for clinical signs, body weights, clinical pathology parameters, and biochemical and pathological evaluations of liver biopsy samples. The effect of HCFC-123 exposure on milk quality (protein and fat concentration) was evaluated. The concentrations of HCFC-123 and the major metabolite, trifluoroacetic acid (TFA), were measured in the blood of the mothers and infants and in the milk. Exposure of monkeys to 1000 ppm HCFC-123 did not result in exposure-related clinical observations, or changes in body weight, appetence and behavior. There were no exposure-related effects on serum triglycerides, cholesterol, or glucose levels. HCFC-123 and TFA were present in milk, although maternal HCFC-123 exposure did not affect milk protein and fat content. In general, HCFC-123 was not detected in maternal or infant blood. TFA was detected in the majority of the mothers and TFA levels in infants ranged from 2 to 6 times higher than levels in the corresponding maternal blood. A pharmacokinetic analysis in a maternal animal indicated a peak concentration of TFA at approximately 1 h post-exposure, with a half-life of approximately 20 h. Liver microsomal P450 and peroxisome oxidase activities showed exposure-related decreases in CYP

  3. Effect of marginal maternal zinc intake on zinc absorption and growth of 3-month-old infant rhesus monkeys

    SciTech Connect

    Loennerdal, B.K.; Keen, C.L.; Bell, J.G.; Golub, M.S.; Hendrickx, A.G.; Gershwin, M.E. )

    1990-09-01

    One compensatory mechanism for marginal zinc intake may be through an enhanced absorption of zinc. Such a compensatory mechanism could be of value to the neonate, as poor zinc nutriture during early life has severe consequences on growth and development. We studied the uptake of zinc by 3-month-old infant rhesus monkeys born to dams fed control diets 100 micrograms of zinc per gram of diet or zinc-restricted diets (4 micrograms of zinc per gram of diet). Zinc uptake/retention was studied by feeding 3-month-old infant monkeys that had fasted an infant formula containing zinc 65 by gavage. Whole body radioactivity was counted immediately after intubation and on days 10 and 17 after intubation. Regardless of dietary group, 65-zinc retention was high, ranging from 33% to 71% of the dose fed to the monkeys. There were no significant differences between the two dietary groups in the percentage of zinc retention at days 10 and 17. Independent of the dietary group, there was no correlation between plasma zinc and zinc absorption. A positive correlation was found between weight gain and zinc retention in the marginal zinc infants, while a negative correlation between weight gain and zinc retention was observed in the control infants. These observations suggest that the mechanisms underlying growth may be different in infants born to dams fed control vs marginal zinc diets.

  4. Effects of 50 MeV/sub d. -->. Be/ neutron irradiation on Rhesus monkey cervical spinal cord

    SciTech Connect

    Jardine, J.H.; Hussey, D.H.; Raulston, G.L.; Chester, D.V.M.; Gleiser, C.A.; Gray, K.N.; Huchton, J.I.; Almond, P.R.

    1980-03-01

    The cervical spinal cords of ten Rhesus monkeys were irradiated with 50 MeV/sub d ..-->.. Be/ neutrons according to one of two dosage schedules: (1) 1300 rad/ sub n..gamma../ in nine fractions over 29 days, and (2) 1550 rad/sub n..gamma../ in nine fractions over 29 days. These doses are equivalent to 4000 rad/sub eq/ and 4800 rad/sub eq/, respectively, with /sup 60/Co using an RBE of 3.1 for late effects (conventional 200 rad per day fractionation). Whereas none of five monkeys that received a spinal cord dose of 1300 rad/sub n..gamma../ developed signs of neurologic dysfunction, all five animals that were irradiated to a dose of 1550 rad/sub n..gamma../ developed significant radiation myelitis. The histopathologic changes correlated well with the clinical observations. All of the animals that received 1550 rad/sub n..gamma../ exhibited severe malacia and moderate to severe demyelination of the white matter of the cervical spinal cord. The histopathologic changes in the monkeys irradiated with 1300 rad/sub n..gamma../ were minimal by comparison.

  5. Loss of D2 receptor binding with age in rhesus monkeys: importance of correction for differences in striatal size.

    PubMed

    Morris, E D; Chefer, S I; Lane, M A; Muzic, R F; Wong, D F; Dannals, R F; Matochik, J A; Bonab, A A; Villemagne, V L; Grant, S J; Ingram, D K; Roth, G S; London, E D

    1999-02-01

    The relation between striatal dopamine D2 receptor binding and aging was investigated in rhesus monkeys with PET. Monkeys (n = 18, 39 to 360 months of age) were scanned with 11C-raclopride; binding potential in the striatum was estimated graphically. Because our magnetic resonance imaging analysis revealed a concomitant relation between size of striatum and age, the dynamic positron emission tomography (PET) data were corrected for possible partial volume (PV) artifacts before parameter estimation. The age-related decline in binding potential was 1% per year and was smaller than the apparent effect if the age-related change in size was ignored. This is the first in vivo demonstration of a decline in dopamine receptor binding in nonhuman primates. The rate of decline in binding potential is consistent with in vitro findings in monkeys but smaller than what has been measured previously in humans using PET. Previous PET studies in humans, however, have not corrected for PV error, although a decline in striatal size with age has been demonstrated. The results of this study suggest that PV correction must be applied to PET data to accurately detect small changes in receptor binding that may occur in parallel with structural changes in the brain.

  6. Age-related effects of bilateral frontal eye fields lesions on rapid eye movements during REM sleep in rhesus monkeys.

    PubMed

    Yu, Shan; Liu, Ning; Zeng, Tao; Tian, Shaohua; Chen, Nanhui; Zhou, Yifeng; Ma, Yuanye

    2004-08-01

    Rapid eye movement (REM) is one of the most characteristic features of REM sleep, but the mechanisms underlying its regulation remain unclear. The present study aims to investigate whether the frontal eye field (FEF) is involved in the regulation of the rapid eye movements during REM sleep. To address this question, we ablated the FEF in four rhesus monkeys and observed the effects of the lesions on sleep architecture. After lesions, two adult monkeys did not show any lesion effect. However, in the other two adolescent monkeys, both the total duration and percentage of the rapid eye movements during REM sleep were decreased moderately. The result suggests that the relation between the FEF and the regulation of the rapid eye movements during REM sleep may be affected by age factor, also indicating that both the functions of the FEF and the mechanisms underlying the control of rapid eye movements during REM sleep might not be the same throughout the whole life span of an animal. PMID:15265590

  7. Discovery of Benzimidazole CYP11B2 Inhibitors with in Vivo Activity in Rhesus Monkeys

    PubMed Central

    2015-01-01

    We report the discovery of a benzimidazole series of CYP11B2 inhibitors. Hit-to-lead and lead optimization studies identified compounds such as 32, which displays potent CYP11B2 inhibition, high selectivity versus related CYP targets, and good pharmacokinetic properties in rat and rhesus. In a rhesus pharmacodynamic model, 32 produces dose-dependent aldosterone lowering efficacy, with no apparent effect on cortisol levels. PMID:26005536

  8. Chronic marijuana smoke exposure in the rhesus monkey. I. Plasma cannabinoid and blood carboxyhemoglobin concentrations and clinical chemistry parameters.

    PubMed

    Slikker, W; Paule, M G; Ali, S F; Scallet, A C; Bailey, J R

    1991-08-01

    This report is the first in a series about a large multidisciplinary study designed to determine whether chronic marijuana (MJ) smoke exposure results in residual behavioral and/or neuropathological alterations in the rhesus monkey. Prior to the initiation of a year of chronic MJ smoke exposure, 64 periadolescent male rhesus monkeys were trained for 1 year to perform five operant behavioral tasks and then divided, according to their performance in these tasks, into four exposure groups (n = 15-16/group): (1) a high dose (HI) group, exposed 7 days/week to the smoke of one standard MJ cigarette; (2) a low dose (LO) group, exposed on weekend days only to the smoke of a standard MJ cigarette; (3) an extracted MJ cigarette (EX) group, exposed 7 days/week to the smoke of one ethanol-extracted MJ cigarette; and (4) a sham group (SH), exposed 7 days/week to sham exposure conditions. Daily exposures for 1 year were accomplished using a mask that covered the subjects' nose and mouth. Average body weights (initially 3.7 +/- 0.5 kg, mean +/- SD) and rates of weight gain (approximately 0.1 kg/month) were the same for all groups throughout the entire experiment. During the first week of exposure, plasma concentrations of delta-9-tetrahydrocannabinol and 11-nor-9-carboxy-THC in the HI group were 59 +/- 7 (mean +/- SE) and 5.5 +/- 1.5 ng/ml, respectively, 45 min after MJ smoke administration and did not change significantly at similar times after exposure throughout the remainder of the year. Whole blood carboxyhemoglobin levels increased to approximately 13% 1 min after exposure to smoke in either the MJ or the EX groups. Comparison of blood chemistry and hematology values before, during, and after exposure indicated no differences for most parameters. During exposure, lymphocytes, alkaline phosphatase and gamma-glutamyl transferase were depressed in the HI group compared to in the SH group. During exposure, aspartate aminotransferase was elevated for both the HI and EX groups

  9. Gonadal and nongonadal mechanisms contribute to the prepubertal hiatus in gonadotropin secretion in the female rhesus monkey (Macaca mulatta).

    PubMed

    Pohl, C R; deRidder, C M; Plant, T M

    1995-07-01

    The present study reexamined the role of the ovary in determining the prepubertal hiatus of gonadotropin secretion in the rhesus monkey. Day- and nighttime blood samples were obtained weekly from neonatally (7-10 days of age) ovariectomized and intact monkeys from birth until 3 yr of age. In the intact monkeys, plasma FSH levels increased during the first month of life, remained elevated until approximately 3 months of age, and then decreased to become undetectable by 7 months of age. Thereafter, plasma FSH remained undetectable until approximately 19 months of age, at which time it again increased to detectable concentrations. In animals ovariectomized as neonates, the developmental pattern in FSH secretion was similar to that in intact animals, but, quantitatively, mean plasma FSH concentrations in the agonadal females were greater than those in the intact control group at all times. Circulating daytime LH concentrations in intact animals were generally below the sensitivity of the assay during the neonatal and prepubertal phases of development, but after 27 months of age, this plasma hormone was measurable on occasion. In neonatally ovariectomized monkeys, daytime LH was elevated during the first month of life, undetectable between 2-20 months of age, and then rose into the adult range by the end of the study. Nocturnal plasma FSH and LH concentrations in agonadal monkeys were generally greater than those during the day at all stages of development. Of particular note was the finding that during the prepubertal hiatus in gonadotropin secretion, when daytime LH levels were mostly immeasurable, nighttime levels of this gonadotropin were consistently elevated. The hypersecretion of gonadotropin during prepubertal development in agonadal animals also occurred when ovariectomy was performed at 61-62 weeks of age. These findings demonstrate that in the female monkey, the open loop activity of the GnRH pulse generator during juvenile development is only partially

  10. Possible modulation of N-methyl-D,L-aspartic acid induced prolactin release by testicular steroids in the adult male rhesus monkey

    SciTech Connect

    Arslan, M.; Rizvi, S.S.R.; Jahan, S.; Zaidi, P.; Shahab, M. )

    1991-01-01

    N-methyl-D,L-aspartic acid (NMA), an agonist of the neurotransmitter glutamate has been shown to acutely stimulate the release of prolactin (PRL) in intact rats and monkeys. To further investigate the role of neuroexcitatory amino acids in PRL secretion, the effects of NMA administration were examined on PRL release in long term orchidectomized adult rhesus monkeys, in both the absence and presence of testosterone. Intact and long term castrated adult male monkeys weighing between 8-13 kg, were implanted with a catheter via the saphenous vein for blood withdrawal and drug infusion. Blood samples were collected at 10 min intervals for 50 min before and 70 min after administration of the drug or vehicle. Plasma PRL concentrations were estimated using radioimmunoassay. Whereas a single iv injection of NMA induced a prompt discharge of PRL in intact monkeys, an identical dose had surprisingly no effect on PRL secretion in orchidectomized animals. On the other hand, plasma PRL increases in response to a challenge dose of thyrotropin releasing hormone were similar in magnitude in the two groups of monkeys. Testosterone replacement in orchidectomized animals by parenteral administration of testosterone enanthate reinitiated the PRL responsiveness to acute NMA stimulation. These results indicate that N-methyl-D-aspartic acid (NMDA) dependent drive to PRL release in the adult male rhesus monkey may be overtly influenced by the sex steroid milieu.

  11. The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells.

    PubMed

    O'Neill, Frank J; Greenlee, John E; Carney, Helen

    2003-05-25

    Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

  12. 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.

  13. 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.

  14. The effects of carbon dioxide inhalation of plasma MHPG, plasma hormones respiratory rate, and behavior in the Rhesus monkey

    SciTech Connect

    Krystal, J.H.; Woods, S.W.; Levesque, M.; Heninger, C.; Heninger, G.R. )

    1989-01-01

    The effects of inhalation of air and 3 concentrations of carbon dioxide (CO{sub 2}) on plasma levels of the norepinephrine metabolite, MHPG, plasma hormones, and behavioral activation were assessed in eight chair-adapted Rhesus monkeys (Macaca mulatta). In comparison to air, inhalation of 5%, 7.5% and 10% CO{sub 2} for 180 minutes produced significant dose-dependent increases in respiratory rate, plasma MHPG, cortisol, growth hormone and prolactin. CO{sub 2} at the 7.5% concentration produced peak changes in behavior at 15, growth hormone at 30, and cortisol and MHPG at 180 minutes without producing changes in prolactin. The lack of previously reported CO{sub 2} induced changes in MHPG, growth hormone and prolactin in humans exposed to 7.5% CO{sub 2} for only 15 minutes, may therefore relate to the relatively short duration of CO{sub 2} exposure.

  15. 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. PMID:26061355

  16. Breadth of cellular and humoral immune responses elicited in rhesus monkeys by multi-valent mosaic and consensus immunogens

    PubMed Central

    Santra, Sampa; Muldoon, Mark; Watson, Sydeaka; Buzby, Adam; Balachandran, Harikrishnan; Carlson, Kevin R.; Mach, Linh; Kong, Wing-Pui; McKee, Krisha; Yang, Zhi-Yong; Rao, Srinivas S.; Mascola, John R.; Nabel, Gary J.; Korber, Bette T.; Letvin, Norman L.

    2013-01-01

    To create an HIV-1 vaccine that generates sufficient breadth of immune recognition to protect against the genetically diverse forms of the circulating virus, we have been exploring vaccines based on consensus and mosaic protein designs. Increasing the valency of a mosaic immunogen cocktail increases epitope coverage but with diminishing returns, as increasingly rare epitopes are incorporated into the mosaic proteins. In this study we compared the immunogenicity of 2-valent and 3-valent HIV-1 envelope mosaic immunogens in rhesus monkeys. Immunizations with the 3-valent mosaic immunogens resulted in a modest increase in the breadth of vaccine-elicited T lymphocyte responses compared to the 2-valent mosaic immunogens. However, the 3-valent mosaic immunogens elicited significantly higher neutralizing responses to Tier 1 viruses than the 2-valent mosaic immunogens. These findings underscore the potential utility of polyvalent mosaic immunogens for eliciting both cellular and humoral immune responses to HIV-1. PMID:22521913

  17. 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.

  18. Development of a high-titer retrovirus producer cell line capable of gene transfer into rhesus monkey hematopoietic stem cells

    SciTech Connect

    Bodine, D.M.; McDonagh, K.T.; Brandt, S.J.; Ney, P.A.; Agricola, B.; Byrne, E.; Nienhuis, A.W. )

    1990-05-01

    Retroviral-mediated gene transfer into primitive hematopoietic cells has been difficult to achieve in large-animal models. The authors have developed an amphotropic producer clone that generates >10{sup 10} recombinant retroviral particles (colony-forming units) per ml of culture medium. Autologous rhesus monkey bone marrow cells were cocultured with either high or low titer producer clones for 4-6 days and reinfused into sublethally irradiated animals. The proviral genome was detected in blood and bone-marrow cells from all three animals reconstituted with cells cocultured with the high-titer producer cells. In contrast, three animals reconstituted with bone marrow cocultured with the low-titer producer clone exhibited no evidence of gene transfer.

  19. Evidence for a partial deficiency of the LDL (apo B,E) receptor within a family of rhesus monkeys with a spontaneous hypercholesterolemia

    SciTech Connect

    Scanu, A.M.; Khalil, A.; Tidore, M.; Kaiser, M.; Pfaffinger, D.; Carey, D.; Dawson, G.

    1987-05-01

    Spontaneous hypercholesterolemia is rare among non-human primates. Through screening of a rhesus monkey colony they have identified a family in which 3 out of its 6 members have a persistent hypercholesterolemia on a cholesterol-free Purina Chow diet and are high responders to a dietary fat challenge. On a basal diet the 3 affected animals also exhibited high plasma levels of LDL and apoB. To shed light on the mechanism of the hypercholesterolemia they have grown in culture fibroblasts from skin biopsies obtained from all members of the rhesus monkey family and 12 control. Binding studies at 4/sup 0/C and ligand blotting experiments using /sup 125/I-LDL of either normolipidemic rhesus monkeys or human subjects have shown that the fibroblasts from the 3 monkeys with a spontaneous hypercholesterolemia have a significant reduction of the number of LDL receptor and to the same extent as fibroblasts derived from subjects with heterozygous FH studied at the same time. The data suggest that the spontaneous elevation of plasma cholesterol observed in the 3 family members is related, at least in part, to a defective uptake of LDL by the LDL receptor pathway.

  20. Evaluation of the Differences of Myocardial Fibers between Acute and Chronic Myocardial Infarction: Application of Diffusion Tensor Magnetic Resonance Imaging in a Rhesus Monkey Model

    PubMed Central

    Wang, Yuqing; Cai, Wei; Wang, Lei; Xia, Rui; Chen, Wei; Zheng, Jie

    2016-01-01

    Objective To understand microstructural changes after myocardial infarction (MI), we evaluated myocardial fibers of rhesus monkeys during acute or chronic MI, and identified the differences of myocardial fibers between acute and chronic MI. Materials and Methods Six fixed hearts of rhesus monkeys with left anterior descending coronary artery ligation for 1 hour or 84 days were scanned by diffusion tensor magnetic resonance imaging (MRI) to measure apparent diffusion coefficient (ADC), fractional anisotropy (FA) and helix angle (HA). Results Comparing with acute MI monkeys (FA: 0.59 ± 0.02; ADC: 5.0 ± 0.6 × 10-4 mm2/s; HA: 94.5 ± 4.4°), chronic MI monkeys showed remarkably decreased FA value (0.26 ± 0.03), increased ADC value (7.8 ± 0.8 × 10-4mm2/s), decreased HA transmural range (49.5 ± 4.6°) and serious defects on endocardium in infarcted regions. The HA in infarcted regions shifted to more components of negative left-handed helix in chronic MI monkeys (-38.3 ± 5.0°–11.2 ± 4.3°) than in acute MI monkeys (-41.4 ± 5.1°–53.1 ± 3.7°), but the HA in remote regions shifted to more components of positive right-handed helix in chronic MI monkeys (-43.8 ± 2.7°–66.5 ± 4.9°) than in acute MI monkeys (-59.5 ± 3.4°–64.9 ± 4.3°). Conclusion Diffusion tensor MRI method helps to quantify differences of mechanical microstructure and water diffusion of myocardial fibers between acute and chronic MI monkey's models. PMID:27587961

  1. Placental transfer and metabolism of 17 alpha-ethynylestradiol-17 beta and estradiol-17 beta in the rhesus monkey

    SciTech Connect

    Slikker, W. Jr.; Bailey, J.R.; Newport, D.; Lipe, G.W.; Hill, D.E.

    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. 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.

  2. Effects of the CRF1 antagonist antalarmin on cocaine self-administration and discrimination in rhesus monkeys.

    PubMed

    Mello, Nancy K; Negus, S Stevens; Rice, Kenner C; Mendelson, Jack H

    2006-12-01

    Cocaine stimulates the rapid release of ACTH, and by inference, CRF in several species, suggesting that the HPA "stress" axis may contribute to the abuse-related effects of cocaine. The effects of a systemically-active CRF(1) receptor antagonist, antalarmin, on cocaine self-administration and cocaine discrimination were examined in rhesus monkeys. Antalarmin's acute (1-10 mg/kg, IV) and chronic (3.2 mg/kg IV) effects on IV cocaine self-administration were studied. The acute effects of 3.2 mg/kg IV antalarmin on the cocaine self-administration dose-effect curve (0.001-0.10 mg/kg/inj) were also examined. The acute effects of antalarmin (5 and 10 mg/kg, IM) on the cocaine discrimination dose-effect curve (0.013-1.3 mg/kg) were examined. Antalarmin did not significantly decrease the reinforcing or the discriminative stimulus effects of cocaine. Acute antalarmin administration produced a dose-dependent but non-significant decrease in self-administration of 0.01 mg/kg/inj cocaine but did not alter the cocaine dose-effect curve. Chronic daily antalarmin treatment did not significantly decrease cocaine-maintained responding. Antalarmin did not significantly alter either the cocaine discrimination dose-effect curve or the time course of the cocaine-training dose. Antalarmin (10 mg/kg) produced sedation, suggesting that it was centrally active, however, it did not attenuate cocaine's abuse-related effects in rhesus monkeys. PMID:17182090

  3. Orbitofrontal and anterior cingulate cortex neurons selectively process cocaine-associated environmental cues in the rhesus monkey.

    PubMed

    Baeg, Eun Ha; Jackson, Mark E; Jedema, Hank P; Bradberry, Charles W

    2009-09-16

    Encounters with stimuli associated with drug use are believed to contribute to relapse. To probe the neurobiology of environmentally triggered drug use, we have conducted single-unit recordings in rhesus monkeys during presentation of two distinct types of drug paired cues that differentially support drug-seeking. The animals were highly conditioned to these cues via exposure during self-administration procedures conducted over a 4 year period. The cues studied were a discriminative cue that signaled response-contingent availability of cocaine, and a discrete cue that was temporally paired with the cocaine infusion (0.1 or 0.5 mg/kg). Two cortical regions consistently activated by cocaine-associated cues in human imaging studies are the orbitofrontal (OFC) and anterior cingulate cortex (ACC), though little is known about cortical neuronal activity responses to drug cues. We simultaneously recorded single-unit activity in OFC and ACC as well as in dorsal striatum in rhesus monkeys during cocaine self-administration. Dorsal striatal neurons were less engaged by drug cues than cortical regions. Between OFC and ACC, distinct functionality was apparent in neuronal responses. OFC neurons preferentially responded to the discriminative cue, consistent with a role in cue-induced drug-seeking. In contrast, the ACC did not respond more to the discriminative cue than to the discrete cue. Also distinct from the OFC, ACC showed sustained firing throughout the 18 s duration of the discrete cue. This pattern of sustained activation in ACC is consistent with a role in reward expectation and/or in mediating behavioral effects of discrete cues paired with drug infusions. PMID:19759309

  4. Selective suppression of cocaine- versus food-maintained responding by monoamine releasers in rhesus monkeys: benzylpiperazine, (+)phenmetrazine, and 4-benzylpiperidine.

    PubMed

    Negus, S S; Baumann, M H; Rothman, R B; Mello, N K; Blough, B E

    2009-04-01

    Monoamine releasers constitute one class of drugs currently under investigation as potential agonist medications for the treatment of cocaine dependence. The efficacy and safety of monoamine releasers as candidate medications may be influenced in part by their relative potency to release dopamine and serotonin, and we reported previously that releasers with approximately 30-fold selectivity for dopamine versus serotonin release may be especially promising. The present study examined the effects of the releasers benzylpiperazine, (+)phenmetrazine, and 4-benzylpiperidine, which have 20- to 48-fold selectivity in vitro for releasing dopamine versus serotonin. In an assay of cocaine discrimination, rhesus monkeys were trained to discriminate 0.4 mg/kg i.m. cocaine from saline in a two-key, food-reinforced procedure. Each of the releasers produced a dose- and time-dependent substitution for cocaine. 4-Benzylpiperidine had the most rapid onset and shortest duration of action. Phenmetrazine and benzylpiperazine had slower onsets and longer durations of action. In an assay of cocaine self-administration, rhesus monkeys were trained to respond for cocaine injections and food pellets under a second order schedule. Treatment for 7 days with each of the releasers produced a dose-dependent and selective reduction in self-administration of cocaine (0.01 mg/kg/injection). The most selective effects were produced by phenmetrazine. Phenmetrazine also produced a downward shift in the cocaine self-administration dose effect curve, virtually eliminating responding maintained by a 30-fold range of cocaine doses (0.0032-0.1 mg/kg/injection) while having only small and transient effects on food-maintained responding. These findings support the potential utility of dopamine-selective releasers as candidate treatments for cocaine dependence. PMID:19151247

  5. Emergence of anti-conflict effects of zolpidem in rhesus monkeys following extended post-injection intervals

    PubMed Central

    Rowlett, James K.; Kehne, John H.; Sprenger, Ken J.; Maynard, George D.

    2010-01-01

    Rationale Zolpidem is a hypnotic drug that binds to γ-aminobutyric acid type A (GABAA) receptors but lacks consistently demonstrable anxiolytic efficacy. Methods Rhesus monkeys (N=4) were trained under a multiple schedule in which food-maintained responding was programmed (18-response, fixed ratio) for a 5-min period, followed by a 5-min period in which the food-maintained responding was suppressed by response-contingent electric shock (20-response fixed ratio). Doses of zolpidem (range= 0.03 to 1.0 mg/kg, i.v.) were administered 5 minutes before the session and responding was re-assessed at 3 additional 20 minute intervals. A similar experiment also was carried out with the non-selective benzodiazepine, triazolam, over a dose range of 0.001 to 0.1 mg/kg, i.v. Results Zolpidem did not engender a significant increase in average rates of suppressed responding at earlier time points; however, rates of non-suppressed responding were robustly decreased. At 45- and 65-min post-injection, zolpidem treatment resulted in a dose-dependent increase in rates of suppressed responding. In contrast, the non-selective benzodiazepine triazolam increased rates of suppressed responding in a dose-dependent manner at all 4 time points, although decreases in non-suppressed responding were less at the later time points. Conclusions These findings suggest that zolpidem has anxiolytic-like effects, but only >25 min after i.v. injection in this rhesus monkey conflict model. It was hypothesized that time-dependent effects on the response rate suppressing properties of zolpidem become tolerant (i.e., acute tolerance). Because anxiolytic-like effects remain stable throughout the session, the absence of rate-decreasing effects may “unmask” anti-conflict effects. PMID:21103864

  6. 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. PMID:26098473

  7. Three-dimensional organization of otolith-ocular reflexes in rhesus monkeys. III. Responses To translation

    NASA Technical Reports Server (NTRS)

    Angelaki, D. E.

    1998-01-01

    The three-dimensional (3-D) properties of the translational vestibulo-ocular reflexes (translational VORs) during lateral and fore-aft oscillations in complete darkness were studied in rhesus monkeys at frequencies between 0.16 and 25 Hz. In addition, constant velocity off-vertical axis rotations extended the frequency range to 0.02 Hz. During lateral motion, horizontal responses were in phase with linear velocity in the frequency range of 2-10 Hz. At both lower and higher frequencies, phase lags were introduced. Torsional response phase changed more than 180 degrees in the tested frequency range such that torsional eye movements, which could be regarded as compensatory to "an apparent roll tilt" at the lowest frequencies, became anticompensatory at all frequencies above approximately 1 Hz. These results suggest two functionally different frequency bandwidths for the translational VORs. In the low-frequency spectrum (<<0.5 Hz), horizontal responses compensatory to translation are small and high-pass-filtered whereas torsional response sensitivity is relatively frequency independent. At higher frequencies however, both horizontal and torsional response sensitivity and phase exhibit a similar frequency dependence, suggesting a common role during head translation. During up-down motion, vertical responses were in phase with translational velocity at 3-5 Hz but phase leads progressively increased for lower frequencies (>90 degrees at frequencies <0.2 Hz). No consistent dependence on static head orientation was observed for the vertical response components during up-down motion and the horizontal and torsional response components during lateral translation. The frequency response characteristics of the translational VORs were fitted by "periphery/brain stem" functions that related the linear acceleration input, transduced by primary otolith afferents, to the velocity signals providing the input to the velocity-to-position neural integrator and the oculomotor plant. The

  8. 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…

  9. Early life stress affects cerebral glucose metabolism in adult rhesus monkeys (Macaca mulatta).

    PubMed

    Parr, Lisa A; Boudreau, Matthew; Hecht, Erin; Winslow, James T; Nemeroff, Charles B; Sánchez, Mar M

    2012-01-01

    Early life stress (ELS) is a risk factor for anxiety, mood disorders and alterations in stress responses. Less is known about the long-term neurobiological impact of ELS. We used [(18)F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) to assess neural responses to a moderate stress test in adult monkeys that experienced ELS as infants. Both groups of monkeys showed hypothalamic-pituitary-adrenal (HPA) axis stress-induced activations and cardiac arousal in response to the stressor. A whole brain analysis detected significantly greater regional cerebral glucose metabolism (rCGM) in superior temporal sulcus, putamen, thalamus, and inferotemporal cortex of ELS animals compared to controls. Region of interest (ROI) analyses performed in areas identified as vulnerable to ELS showed greater activity in the orbitofrontal cortex of ELS compared to control monkeys, but greater hippocampal activity in the control compared to ELS monkeys. Together, these results suggest hyperactivity in emotional and sensory processing regions of adult monkeys with ELS, and greater activity in stress-regulatory areas in the controls. Despite these neural responses, no group differences were detected in neuroendocrine, autonomic or behavioral responses, except for a trend towards increased stillness in the ELS monkeys. Together, these data suggest hypervigilance in the ELS monkeys in the absence of immediate danger. PMID:22682736

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

    PubMed

    Johnson, Reed F; Hammoud, Dima A; Lackemeyer, Matthew G; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K; Janosko, Krisztina B; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E; Jahrling, Peter B

    2015-07-01

    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 log10 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. PMID:25776759

  11. Comparison of the effects of methamphetamine, bupropion, and methylphenidate on the self-administration of methamphetamine by rhesus monkeys.

    PubMed

    Schindler, Charles W; Gilman, Joanne P; Panlilio, Leigh V; McCann, David J; Goldberg, Steven R

    2011-02-01

    The effectiveness of methadone as a treatment for opioid abuse and nicotine preparations as treatments for tobacco smoking has led to an interest in developing a similar strategy for treating psychostimulant abuse. The current study investigated the effects of three such potential therapies on intravenous methamphetamine self-administration (1 - 30 μg/kg/injection) in rhesus monkeys. When given as a presession intramuscular injection, a high dose of methamphetamine (1.0 mg/kg) decreased intravenous methamphetamine self-administration but did not affect responding for a food reinforcer during the same sessions. However, the dose of intramuscular methamphetamine required to reduce intravenous methamphetamine self-administration exceeded the cumulative amount taken during a typical self-administration session, and pretreatment with a low dose of methamphetamine (0.3 mg/kg) actually increased self-administration in some monkeys at the lower self-administration dose. Like pretreatment with methamphetamine, pretreatment with bupropion (3.2 mg/kg) decreased methamphetamine self-administration but did not affect responding for food. Pretreatment with methylphenidate (0.56 mg/kg) did not significantly alter methamphetamine self-administration. These results suggest that some agonist-like agents can decrease methamphetamine self-administration. Although the most robust effects occurred with a high dose of methamphetamine, safety and abuse liability considerations suggest that bupropion should also be considered for further evaluation as a methamphetamine addiction treatment.

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

    PubMed Central

    Hammoud, Dima A.; Lackemeyer, Matthew G.; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K.; Janosko, Krisztina B.; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E.; Jahrling, Peter B.

    2015-01-01

    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 log10 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. PMID:25776759

  13. Limited replication of yellow fever 17DD and 17D-Dengue recombinant viruses in rhesus monkeys.

    PubMed

    Trindade, Gisela F; Marchevsky, Renato S; Fillipis, Ana M B de; Nogueira, Rita M R; Bonaldo, Myrna C; Acero, Pedro C; Caride, Elena; Freire, Marcos S; Galler, Ricardo

    2008-06-01

    For the development of safe live attenuated flavivirus vaccines one of the main properties to be established is viral replication. We have used real-time reverse transcriptase-polymerase chain reaction and virus titration by plaque assay to determine the replication of yellow fever 17DD virus (YFV 17DD) and recombinant yellow fever 17D viruses expressing envelope proteins of dengue virus serotypes 2 and 4 (17D-DENV-2 and 17D-DENV-4). Serum samples from rhesus monkeys inoculated with YFV 17DD and 17D-DENV chimeras by intracerebral or subcutaneous route were used to determine and compare the viremia induced by these viruses. Viral load quantification in samples from monkeys inoculated by either route with YFV 17DD virus suggested a restricted capability of the virus to replicate reaching not more than 2.0 log10 PFU mL(-1) or 3.29 log10 copies mL(-1). Recombinant 17D-dengue viruses were shown by plaquing and real-time PCR to be as attenuated as YF 17DD virus with the highest mean peak titer of 1.97 log10 PFU mL(-1) or 3.53 log10 copies mL(-1). These data serve as a comparative basis for the characterization of other 17D-based live attenuated candidate vaccines against other diseases.

  14. Super-additive interaction of the reinforcing effects of cocaine and H1-antihistamines in rhesus monkeys.

    PubMed

    Wang, Zhixia; Woolverton, William L

    2009-02-01

    Histamine H1 receptor antagonists can be sedating and have behavioral effects, including reinforcing and discriminative stimulus effects in non-humans, that predict abuse liability. Previous research has suggested that antihistamines can enhance the effects of some drugs of abuse. We have reported a synergistic interaction between cocaine and diphenhydramine (DPH) in a self-administration assay with monkeys. The present study was designed to extend those findings to other combinations of cocaine and DPH, and to the mixture of cocaine and another H1-antihistamine, pyrilamine. Rhesus monkeys were prepared with chronic i.v. catheters and allowed to self-administer cocaine, DPH or pyrilamine alone or as mixtures under a progressive-ratio schedule of reinforcement. Cocaine, DPH and pyrilamine alone maintained self-administration and cocaine was the stronger reinforcer. When cocaine was combined with DPH or pyrilamine in a 1:1, 1:2 or 2:1 ratio of the ED(50)s, the combinations were super-additive as reinforcers. Reinforcing strength of the combinations was greater than that of the antihistamines alone but not greater than cocaine. The data support the prediction that the combination of cocaine and histamine H1 receptor antagonists could have enhanced potential for abuse relative to either drug alone. The interaction may involve dopamine systems in the CNS. PMID:18930758

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

    PubMed

    Johnson, Reed F; Hammoud, Dima A; Lackemeyer, Matthew G; Yellayi, Srikanth; Solomon, Jeffrey; Bohannon, Jordan K; Janosko, Krisztina B; Jett, Catherine; Cooper, Kurt; Blaney, Joseph E; Jahrling, Peter B

    2015-07-01

    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 log10 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.

  16. Effects of daily morphine administration and deprivation on choice and demand for remifentanil and cocaine in rhesus monkeys.

    PubMed

    Wade-Galuska, Tammy; Galuska, Chad M; Winger, Gail

    2011-01-01

    Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been applied to this question. The present study assessed whether mild morphine withdrawal would increase demand for or choice of remifentanil or cocaine. Four rhesus monkeys chose between remifentanil and cocaine during daily sessions. Demand curves for both drugs were subsequently obtained. The effects of daily injections of 3.2 mg/kg morphine on both choice and demand for these drugs was assayed 3 and 20.5 hr after each morphine injection, and then during a postmorphine period. Three hours following morphine injections, choice of remifentanil over cocaine decreased and demand for remifentanil--but not cocaine--became more elastic. During morphine withdrawal (20.5 hr postinjection), choice of remifentanil increased and remifentanil demand became more inelastic in 3 of 4 monkeys. Cocaine demand also became more inelastic during this period. Four to five weeks following the morphine regimen, demand for both drugs was more inelastic relative to the initial determination. The results suggest that both the relative and absolute reinforcing effectiveness of remifentanil decreased following morphine administration and increased during morphine withdrawal. The absolute reinforcing effectiveness of cocaine also increased during morphine withdrawal. In addition, extended exposure to drug self-administration and/or exposure to the morphine regimen produced long-term increases in demand for both drugs. PMID:21541117

  17. 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

  18. 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

  19. Associations between Parity, Hair Hormone Profiles during Pregnancy and Lactation, and Infant Development in Rhesus Monkeys (Macaca mulatta).

    PubMed

    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 mothers

  20. PET imaging of dopamine D2 receptor and transporter availability during acquisition of cocaine self-administration in rhesus monkeys.

    PubMed

    Czoty, Paul W; Gage, H Donald; Nader, Susan H; Reboussin, Beth A; Bounds, Michael; Nader, Michael A

    2007-03-01

    Previous studies have demonstrated that cocaine use alters availability of brain dopamine D2 receptors (D2R) and transporters (DAT). The present study examined the effects of low doses of cocaine on this neuroadaptation. Using positron emission tomography (PET), D2R and DAT availability in the caudate nucleus (Cd), putamen (Pt), anterior cingulate cortex (ACC), and amygdala (AMY) were assessed before and after monkeys acquired cocaine self-administration. Twelve rhesus monkeys were trained to self-administer intravenous cocaine (0.03 mg/kg per injection) under conditions that resulted in low drug intakes. PET scans using radiotracers targeting D2R ([F]fluoroclebopride, FCP) or DAT ([F]-(+)-N-(4-fluorobenzyl)-2β-propanoyl-3β-(4-chlorophenyl)tropane, FCT) were performed when monkeys were cocaine naive and after 9 weeks of self-administration. Before self-administration, D2R availability was significantly higher only in left vs. right Cd, whereas DAT availability was higher in left vs. right Cd, Pt, and ACC. Nonetheless, after cocaine exposure, left-right differences in D2R were apparent in 3 of 4 regions, but only in the ACC for DAT availability. Self-administration of this dose of cocaine did not significantly affect DAT availability in any region and only decreased D2R availability in the ACC. These results demonstrate lateralization of D2R and DAT availability in brain areas that mediate cocaine self-administration, even under conditions in which cocaine does not affect overall receptor availability. PMID:21768930

  1. Effects of the selective delta opioid agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys.

    PubMed

    Do Carmo, Gail Pereira; Mello, Nancy K; Rice, Kenner C; Folk, John E; Negus, S Stevens

    2006-10-10

    Delta agonists such as SNC80 ((+)-4-[(aR)-a-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide) produce some cocaine-like behavioral effects and warrant evaluation as candidate "agonist" medications for cocaine abuse. The present study examined acute and chronic effects of the systemically active delta agonist SNC80 on cocaine- and food-maintained responding in rhesus monkeys. Acute SNC80 (0.32-3.2 mg/kg, i.m.) pretreatment dose-dependently decreased cocaine self-administration (0.0032 mg/kg/injection), but doses of SNC80 that decreased cocaine self-administration also decreased food-maintained responding. In chronic studies, SNC80 (0.32-3.2 mg/kg/h, i.v.) was delivered for 7 days, and food or cocaine (0.01 mg/kg/injection) was available during 4 daily components of food availability and 4 daily components of drug availability. Chronic SNC80 (1.8 mg/kg/h) tended to decrease cocaine self-administration but produced greater reductions in food-maintained responding. A higher dose of 3.2 mg/kg/h SNC80 eliminated both cocaine- and food-maintained responding and produced profound sedation in one monkey and was not tested in other monkeys. These findings indicate that SNC80 produced dose-dependent and non-selective reductions in cocaine self-administration. These results suggest that SNC80 is unlikely to be useful as a treatment for cocaine dependence. PMID:16934797

  2. Amelioration of the cardiovascular effects of cocaine in rhesus monkeys by a long-acting mutant form of cocaine esterase.

    PubMed

    Collins, Gregory T; Carey, Kathy A; Narasimhan, Diwahar; Nichols, Joseph; Berlin, Aaron A; Lukacs, Nicholas W; Sunahara, Roger K; Woods, James H; Ko, Mei-Chuan

    2011-04-01

    A long-acting mutant form of a naturally occurring bacterial cocaine esterase (T172R/G173Q CocE; double mutant CocE (DM CocE)) has previously been shown to antagonize the reinforcing, convulsant, and lethal effects of cocaine in rodents. However, the effectiveness and therapeutic characteristics of DM CocE in nonhuman primates, in a more clinically relevant context, are unknown. The current studies were aimed at (1) characterizing the cardiovascular effects of cocaine in freely moving rhesus monkeys, (2) evaluating the capacity of DM CocE to ameliorate these cocaine-induced cardiovascular effects when administered 10 min after cocaine, and (3) assessing the immunological responses of monkeys to DM CocE following repeated administration. Intravenous administration of cocaine produced dose-dependent increases in mean arterial pressure (MAP) and heart rate (HR) that persisted throughout the 2-h observation period following a dose of 3.2 mg/kg cocaine. Cocaine failed to produce reliable changes in electrocardiograph (ECG) parameters, body temperature, and locomotor activity. DM CocE produced a rapid and dose-dependent amelioration of the cardiovascular effects, with saline-like MAP measures restored within 5-10 min, and saline-like HR measures restored within 20-40 min of DM CocE