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Sample records for adolescent rhesus monkeys

  1. 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.

  2. 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.

  3. Effects of confined space and near vision stimulation on refractive status and vitreous chamber depth in adolescent rhesus monkeys.

    PubMed

    Leng, Yunxia; Lan, Weizhong; Yu, Keming; Liu, Bingqian; Yang, Zhikuan; Li, Zheng; Zhong, Xingwu; Zhang, Shaochong; Ge, Jian

    2010-12-01

    This study aimed to investigate the effects of sustained near vision stimulation, on the refractive development and elongation of the vitreous chamber in adolescent rhesus monkeys. A total of 12 adolescent rhesus monkeys (1.5-2.0 years old) were randomly assigned to 3 groups. In groups A (n=4) and B (n=4), monkeys were reared in close-vision cages for 8 and 4 h d(-1), respectively; tiny granules were added on the cage floor to avoid visual deprivation and to encourage near gaze. In group C (n=4), monkeys were reared in open-vision cages, with non-granule food as a control. Vitreous chamber depth, refractive status, and corneal refractive power were assessed over 18 months. Paired t-test was used to compare the differences and a P-value<0.05 was considered to be statistically significant. In group A, vitreous chamber depth and optical axis elongated significantly, and refractive error shifted towards myopia during the observation period. In group B, vitreous chambers and optical axis elongated but the refractive power did not show significant changes. In group C, there was no significant elongation in vitreous chambers and optical axis, and the refractive power changed slightly towards hypermetropia. There were no significant changes in corneal refractive power in each group. Sustained near vision can promote vitreous chamber growth and induce myopic shifts in refractive power in adolescent monkeys. Our results demonstrate the potential for a primate model of near-work-related myopia.

  4. 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.

  5. 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.

  6. Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy

    PubMed Central

    2013-01-01

    Background Early adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones. Methods Diffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity. Results We found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression. Conclusions These findings highlight the

  7. 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.

  8. Long-term exposure to oral methylphenidate or dl-amphetamine mixture in peri-adolescent rhesus monkeys: effects on physiology, behavior, and dopamine system development.

    PubMed

    Soto, Paul L; Wilcox, Kristin M; Zhou, Yun; Kumar, Anil; Ator, Nancy A; Riddle, Mark A; Wong, Dean F; Weed, Michael R

    2012-11-01

    The stimulants methylphenidate and amphetamine are used to treat children with attention deficit/hyperactivity disorder over important developmental periods, prompting concerns regarding possible long-term health impact. This study assessed the effects of such a regimen in male, peri-adolescent rhesus monkeys on a variety of cognitive/behavioral, physiological, and in vivo neurochemical imaging parameters. Twice daily (0900 and 1200 hours), for a total of 18 months, juvenile male monkeys (8 per group) consumed either an unadulterated orange-flavored solution, a methylphenidate solution, or a dl-amphetamine mixture. Doses were titrated to reach blood/plasma levels comparable to therapeutic levels in children. [¹¹C]MPH and [¹¹C]raclopride dynamic PET scans were performed to image dopamine transporter and D₂-like receptors, respectively. Binding potential (BP(ND)), an index of tracer-specific binding, and amphetamine-induced changes in BP(ND) of [¹¹C]raclopride were estimated by kinetic modeling. There were no consistent differences among groups on the vast majority of measures, including cognitive (psychomotor speed, timing, inhibitory control, cognitive flexibility), general activity, physiological (body weight, head circumference, crown-to-rump length), and neurochemical (ie, developmental changes in dopamine transporter, dopamine D₂ receptor density, and amphetamine-stimulated dopamine release were as expected). Cytogenetic studies indicated that neither drug was a clastogen in rhesus monkeys. Thus, methylphenidate and amphetamine at therapeutic blood/plasma levels during peri-adolescence in non-human primates have little effect on physiological or behavioral/cognitive development.

  9. Canine distemper outbreak in rhesus monkeys, China.

    PubMed

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

    2011-08-01

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

  10. 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

  11. The amplitude of nocturnal melatonin concentrations is not decreased by oestradiol and does not alter reproductive function in adolescent or adult female rhesus monkeys.

    PubMed

    Wilson, M E; Lackey, S; Chikazawa, K; Gordon, T P

    1993-05-01

    Nocturnal concentrations of melatonin in serum decline significantly with advancing pubertal development in both children and non-human primates and elevated levels may be associated with anovulation in adults. Three studies, using female rhesus monkeys, were performed to determine whether (1) the decline in nocturnal melatonin concentrations in adolescents was due to maturational increases in serum oestradiol, (2) the experimental elevation in nocturnal melatonin would delay the normal progression of puberty in post-menarchial monkeys, and (3) the experimental elevation in nocturnal melatonin would disrupt normal ovulatory function in adults. In experiment 1, juvenile female rhesus monkeys, housed indoors in a fixed photoperiod (12 h light:12 h darkness), were assigned randomly to one of two treatment groups: ovariectomized with no replacement therapy (control; n = 4) or ovariectomized with oestradiol replacement therapy maintaining oestradiol at approximately 90 pmol/l (treated; n = 8). Twenty-four hour as well as daytime serum samples were collected from 19 to 35 months of age. Nocturnal melatonin concentrations declined significantly in all females with advancing chronological age and this change was unaffected by oestradiol treatment. The decline in nocturnal melatonin concentrations occurred, on average, 2.0 +/- 0.2 months after the initial rise in serum LH in control females and 6.0 +/- 0.8 months in treated females. Furthermore, this decline in night-time melatonin was not related to significant developmental changes in body weight. In experiment 2, control (n = 6) and melatonin-treated (treated; n = 6) adolescent female monkeys were studied from -30 to +105 days from menarche. Beginning at 45 days following menarche, treated females received 30 days of nocturnal melatonin infusion to elevate levels to prepubertal values. Developmental changes in perineal swelling and coloration as well as serum oestradiol and insulin-like growth factor-I (IGF-I) were

  12. 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…

  13. 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.

  14. IGF-I administration advances the decrease in hypersensitivity to oestradiol negative feedback inhibition of serum LH in adolescent female rhesus monkeys.

    PubMed

    Wilson, M E

    1995-04-01

    Developmental increases in serum LH were assessed in female rhesus monkeys to test the hypotheses that (1) the final stages of puberty are characterized by a decrease in hypersensitivity to oestradiol negative feedback of LH and (2) that increases in IGF-I secretion accelerate this decrease in hypersensitivity. In order to test the first hypothesis, serum LH in the absence of oestradiol and in response to three doses of oestradiol were compared between ovariectomized adult (n = 6) and adolescent female monkeys (control group; n = 6). The control females were not treated with oestradiol until serum LH had risen to within the 95% confidence interval of serum LH observed in ovariectomized adults. Doses of oestradiol achieved serum levels of approximately 80 ('low'), 160 ('intermediate'), and 250 ('high') pmol/l. For control group females, treatment with the next higher dose of oestradiol was not initiated until serum LH was no longer suppressed by the lower dose. Treatment with oestradiol produced a dose-dependent suppression in serum LH in adults. In contrast, low-dose oestradiol maximally suppressed serum LH throughout the initial treatment period in the control group compared with the adult females. The low oestradiol dose effectively suppressed serum LH throughout the study period in 4/6 of the control group and became ineffective at suppressing LH after 8 months of treatment in 2/6 control group females. Initiation of the intermediate dose of oestradiol to these females again maximally suppressed LH compared with adult females. In order to determine whether IGF-I regulates this change in hypersensitivity to oestradiol negative feedback, a second group of ovariectomized, adolescent monkeys (n = 6) were treated chronically with IGF-I to elevate serum IGF-I levels above those of control group females. Using the same protocol described for the control females, developmental changes in serum LH in the absence of oestradiol and in response to oestradiol negative

  15. 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

  16. Turnover of human and monkey plasma kininogens in rhesus monkeys.

    PubMed Central

    Yamada, T; Wing, D A; Pierce, J V; Pettit, G W

    1979-01-01

    The normal metabolic turnover of plasma kininogens was studied by measuring the disappearance of intravenously administered radiolabeled human and monkey plasma kininogens from the circulation of healthy adult rhesus monkeys. Curves obtained by plotting log radioactivity against time could be expressed as double exponential equations, with the first term representing diffusion, and the second, catabolism. No significant difference between the turnovers of human and monkey kininogens was observed. The difference between the t1/2 of high molecular weight kininogen (25.95 +/- 1.60 h) (mean +/- SEM) and that of low molecular weight kininogen (18.94 +/- 1.93 h) was only marginally significant (P less than 0.05). In contrast, a highly significant (P less than 0.001) difference in their mean catabolic rates (1.12 +/- 0.08 d-1 for high molecular weight kininogen vs. 2.07 +/- 0.09 d-1 for low molecular weight kininogen) was observed. These differences between the two kininogens were attributed to differences in their distribution between the intra- and extravascular pools. Studies of kininogen turnover will be useful in elucidating the in vivo functions of the various kininogens in health as well as during clinical illness. PMID:105015

  17. 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.

  18. Accommodation dynamics in aging rhesus monkeys.

    PubMed

    Croft, M A; Kaufman, P L; Crawford, K S; Neider, M W; Glasser, A; Bito, L Z

    1998-12-01

    Accommodation, the mechanism by which the eye focuses on near objects, is lost with increasing age in humans and monkeys. This pathophysiology, called presbyopia, is poorly understood. We studied aging-related changes in the dynamics of accommodation in rhesus monkeys aged 4-24 yr after total iridectomy and midbrain implantation of an electrode to permit visualization and stimulation, respectively, of the eye's accommodative apparatus. Real-time video techniques were used to capture and quantify images of the ciliary body and lens. During accommodation in youth, ciliary body movement was biphasic, lens movement was monophasic, and both slowed as the structures approached their new steady-state positions. Disaccommodation occurred more rapidly for both ciliary body and lens, but with longer latent period, and slowed near the end point. With increasing age, the amplitude of lens and ciliary body movement during accommodation declined, as did their velocities. The latent period of lens and ciliary body movements increased, and ciliary body movement became monophasic. The latent period of lens and ciliary body movement during disaccommodation was not significantly correlated with age, but their velocity declined significantly. The age-dependent decline in amplitude and velocity of ciliary body movements during accommodation suggests that ciliary body dysfunction plays a role in presbyopia. The age changes in lens movement could be a consequence of increasing inelasticity or hardening of the lens, or of age changes in ciliary body motility.

  19. 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.

  20. 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.

  1. Norovirus GII.17 Natural Infections in Rhesus Monkeys, China

    PubMed Central

    He, Zhanlong; Liu, Bo; Tao, Yufen; Li, Chao; Xia, Ming; Zhong, Weiming; Jiang, Xi

    2017-01-01

    Noroviruses are a leading viral cause of acute gastroenteritis among humans. During the 2014–15 epidemic season, norovirus GII.17 was detected in rhesus monkeys in China. Genetic, structural, and challenge studies revealed virus mutations and verified the infections. Thus, cross-species transmission may occur, and monkeys may be a virus reservoir. PMID:28102802

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

    DOE PAGES

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

    2014-11-19

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

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

    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.

  4. A more consistent intraluminal rhesus monkey model of ischemic stroke

    PubMed Central

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-01-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research. PMID:25657726

  5. A more consistent intraluminal rhesus monkey model of ischemic stroke.

    PubMed

    Zhao, Bo; Shang, Guowei; Chen, Jian; Geng, Xiaokun; Ye, Xin; Xu, Guoxun; Wang, Ju; Zheng, Jiasheng; Li, Hongjun; Akbary, Fauzia; Li, Shengli; Lu, Jing; Ling, Feng; Ji, Xunming

    2014-12-01

    Endovascular surgery is advantageous in experimentally induced ischemic stroke because it causes fewer cranial traumatic lesions than invasive surgery and can closely mimic the pathophysiology in stroke patients. However, the outcomes are highly variable, which limits the accuracy of evaluations of ischemic stroke studies. In this study, eight healthy adult rhesus monkeys were randomized into two groups with four monkeys in each group: middle cerebral artery occlusion at origin segment (M1) and middle cerebral artery occlusion at M2 segment. The blood flow in the middle cerebral artery was blocked completely for 2 hours using the endovascular microcoil placement technique (1 mm × 10 cm) (undetachable), to establish a model of cerebral ischemia. The microcoil was withdrawn and the middle cerebral artery blood flow was restored. A reversible middle cerebral artery occlusion model was identified by hematoxylin-eosin staining, digital subtraction angiography, magnetic resonance angiography, magnetic resonance imaging, and neurological evaluation. The results showed that the middle cerebral artery occlusion model was successfully established in eight adult healthy rhesus monkeys, and ischemic lesions were apparent in the brain tissue of rhesus monkeys at 24 hours after occlusion. The rhesus monkeys had symptoms of neurological deficits. Compared with the M1 occlusion group, the M2 occlusion group had lower infarction volume and higher neurological scores. These experimental findings indicate that reversible middle cerebral artery occlusion can be produced with the endovascular microcoil technique in rhesus monkeys. The M2 occluded model had less infarction and less neurological impairment, which offers the potential for application in the field of brain injury research.

  6. 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…

  7. MAC of xenon and halothane in rhesus monkeys.

    PubMed

    Whitehurst, S L; Nemoto, E M; Yao, L; Yonas, H

    1994-10-01

    Local cerebral blood flow (LCBF) maps produced by 33% xenon-enhanced computed tomographic scanning (Xe/CT LCBF) are useful in the clinical diagnosis and management of patients with cerebrovascular disorders. However, observations in humans that 25-35% xenon (Xe) inhalation increases cerebral blood flow (CBF) have raised concerns that Xe/CT LCBF measurements may be inaccurate and that Xe inhalation may be hazardous in patients with decreased intracranial compliance. In contrast, 33% Xe does not increase CBF in rhesus monkeys. To determine whether this interspecies difference in the effect of Xe on CBF correlates with an interspecies difference in the anesthetic potency of Xe, we measured the minimum alveolar concentration (MAC) of Xe preventing movement to a tail-clamp stimulus in rhesus monkeys. Using a standard protocol for the determination of MAC in animals, we first measured the MAC of halothane (n = 5), and then used a combination of halothane and Xe to measure the MAC of Xe (n = 7). The halothane MAC was 0.99 +/- 0.12% (M +/- SD), and the Xe MAC was 98 +/- 15%. These results suggest that the MAC of Xe in rhesus monkeys is higher than the reported human Xe MAC value of 71%. Thus the absence of an effect of 33% Xe on CBF in the rhesus monkey may be related to its lower anesthetic potency.

  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. Pathology of Bolivian Hemorrhagic Fever in the Rhesus Monkey

    PubMed Central

    Terrell, Timothy G.; Stookey, James L.; Eddy, Gerald A.; Kastello, Michael D.

    1973-01-01

    Gross and microscopic lesions associated with Bolivan hemorrhagic fever virus infection in the rhesus monkey were studied in 10 animals which died following inoculation. Gross lesions included skin rash, lymphadenopathy, splenomegaly, meningeal edema, hydropericardium and enlarged friable livers. Hemorrhagic manifestations of the infection were not consistently observed, but hemorrhages were present in the skin, heart, brain and nares in some monkeys. Histopathologic lesions were fairly consistent. Hepatic necrosis with the presence of acidophilic hyaline bodies, necrotizing enteritis, epithelial necrosis and adrenal cortical necrosis were present in all monkeys. Those monkeys which died after the seventeenth day of infection had nonsupurative meningoencephalitis; lymphoid necrosis was present in 3 monkeys that died after day 18. Other microscopic lesions included myocardial degeneration, lymphoid and reticuloendothelial cell hyperplasia and lymphoid depletion. Most of the histopathologic lesions described in human autopsy material were reproduced; however, the necrosis in the skin and oral mucosa, mucosa of the gastrointestinal tract and the adrenal cortex have not been described in man. Despite these apparent discrepancies the results of this investigation indicate that the rhesus monkey is a good experimental model for the study of Bolivian hemorrhagic fever infection. ImagesFig 12Fig 13Fig 1Fig 2Fig 3Fig 4Fig 5Fig 6Fig 7Fig 8Fig 9Fig 10Fig 11 PMID:4202335

  10. Gonadectomy increases neurogenesis in the male adolescent rhesus macaque hippocampus.

    PubMed

    Allen, K M; Fung, S J; Rothmond, D A; Noble, P L; Weickert, C Shannon

    2014-02-01

    New neurons are continuously produced in the subgranular zone of the adult hippocampus and can modulate hippocampal plasticity across life. Adolescence is characterized by dramatic changes in sex hormone levels, and social and emotional behaviors. It is also an age for increased risk of psychiatric disorders, including schizophrenia, which may involve altered hippocampal neurogenesis. The extent to which testosterone and other testicular hormones modulate hippocampal neurogenesis and adolescent behavioral development is unclear. This study aimed to determine if removal of testicular hormones during adolescence alters neurogenesis in the male rhesus macaque hippocampus. We used stereology to examine levels of cell proliferation, cell survival and neuronal differentiation in late adolescent male rhesus macaques (4.6-yrs old) that had previously been gonadectomized or sham operated prior to puberty (2.4-yrs old). While the absence of adolescent testicular hormones had no effect on cell proliferation, cell survival was increased by 65% and indices of immature neuronal differentiation were increased by 56% in gonadectomized monkeys compared to intact monkeys. We show for the first time that presence of circulating testicular hormones, including testosterone, may decrease neuronal survival in the primate hippocampus during adolescence. Our findings are in contrast to existing studies in adults where testosterone tends to be a pro-survival factor and demonstrate that testicular hormones may reduce hippocampal neurogenesis during the age typical of schizophrenia onset.

  11. Recovery from unilateral labyrinthectomy in rhesus monkey.

    PubMed

    Fetter, M; Zee, D S

    1988-02-01

    1. We recorded eye movements in six rhesus monkeys before and after unilateral labyrinthectomy and quantified the compensation for both the static and the dynamic disturbances of the vestibuloocular reflex (VOR). 2. When first recorded after labyrinthectomy (18-20 h postlesion), all animals had a spontaneous nystagmus with mean slow-phase velocities ranging from 24 to 54 degrees/s measured in darkness and 0-4 degrees/s measured in the light. The level of nystagmus diminished quickly, and by postoperative day 25 mean values ranged from 4 to 22 degrees/s, measured in darkness. The waveform of individual slow phases was variable, but in the first postoperative week its trajectory usually showed an increasing, or an increasing then decreasing, velocity. This finding indicates that peripheral vestibular lesions can alter the function of the ocular motor eye-position integrator. 3. The VOR gain (eye velocity/head velocity, corrected for spontaneous nystagmus) during rotations (30-300 degrees/s) in the dark was diminished from nearly 1.0 preoperatively to approximately 0.5 when first measured after labyrinthectomy, except for rotations toward the lesioned side at high speeds for which the gain was even lower. Within the first few postoperative days, for rotations toward the intact side, the VOR gain increased rapidly, to approximately 0.8. For rotations toward the lesioned side similar behavior was noted for stimuli of 30-60 degrees/s, but at higher velocities compensation proceeded more slowly. By 3 mo postoperatively gains had reached values ranging from 0.77 to 1.03 for rotations toward the intact side and from 0.61 to 0.98 for rotations toward the lesioned side. Values were higher for lower-velocity stimuli. 4. Caloric testing with ice water in the unoperated ear elicited nystagmus with a mean value of maximum slow-phase velocity of 129 degrees/s preoperatively and 195 degrees/s 3 mo postoperatively. There was no caloric response on the lesioned side. From the

  12. Orientation perception in rhesus monkeys (Macaca mulatta).

    PubMed

    Wakita, Masumi

    2008-07-01

    It was previously demonstrated that monkeys divide the orientation continuum into cardinal and oblique categories. However, it is still unclear how monkeys perceive within-category orientations. To better understand monkeys' perception of orientation, two experiments were conducted using five monkeys. In experiment 1, they were trained to identify either one cardinal or one oblique target orientation out of six orientations. The results showed that they readily identified the cardinal target whether it was oriented horizontally or vertically. However, a longer training period was needed to identify the oblique target orientation regardless of its degree and direction of tilt. In experiment 2, the same monkeys were trained to identify two-oblique target orientations out of six orientations. These orientations were paired, either sharing the degree of tilt, direction of tilt, or neither property. The results showed that the monkeys readily identified oblique orientations when they had either the same degree or direction of tilt. However, when the target orientations had neither the same degree nor direction of tilt, the animals had difficulty in identifying them. In summary, horizontal and vertical orientations are individually processed, indicating that monkeys do not have a category for cardinal orientation, but they may recognize cardinal orientations as non-obliques. In addition, monkeys efficiently abstract either the degree or the direction of tilt from oblique orientations, but they have difficulty combining these features to identify an oblique orientation. Thus, not all orientations within the oblique category are equally perceived.

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

    DTIC Science & Technology

    1983-04-01

    ýfj NAMRL 1295 ERUPTION OF PERMANENT DENTITION IN RHESUS MONKEYS EXPOSED TO ELF FIELDS Weli Tony D. David, Gregory A. Harris, and John A. Bley, Jr...distribution unlimited. ERUPTION OF PERMANENT DENTITION IN RHESUS MONKEYS EXPOSED TO ELF FIELDS Tony D. David, Gregory A. Harris, and John A. Bley, Jr. Naval...mechanism involved. This interim report concerns the maturation of the permanent dentition in rhesus monkeys. Information dealing with tooth development is

  14. 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.

  15. Naturally occurring melioidosis in a colonized rhesus monkey (Macaca mulatta).

    PubMed

    Fritz, P E; Miller, J G; Slayter, M; Smith, T J

    1986-10-01

    An aged wild-caught male rhesus monkey (Macaca mulatta), maintained in a research facility for 10 years, developed bilateral pelvic limb paralysis without other signs of disease. Unresponsive to therapy, the monkey was killed and necropsied. Chronic inflammation with osteolysis of thoracic vertebrae 10-13 was observed. Pseudomonas pseudomallei was cultured and identified from cerebrospinal fluid obtained at the site of the thoracic lesion. This Gram-negative bacterium can cause infection in animals and man and may remain latent for years before the appearance of clinical signs.

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

    PubMed Central

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

    2014-01-01

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

  17. 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.

  18. 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

  19. Rhesus monkey brain imaging through intact skull with thermoacoustic tomography.

    PubMed

    Xu, Yuan; Wang, Lihong V

    2006-03-01

    Two-dimensional microwave-induced thermoacoustic tomography (TAT) is applied to imaging the Rhesus monkey brain through the intact skull. To reduce the wavefront distortion caused by the skull, only the low-frequency components of the thermoacoustic signals (< 1 MHz) are used to reconstruct the TAT images. The methods of signal processing and image reconstruction are validated by imaging a lamb kidney. The resolution of the system is found to be 4 mm when we image a 1-month-old monkey head containing inserted needles. We also image the coronal and axial sections of a 7-month-old monkey head. Brain features that are 3 cm deep in the head are imaged clearly. Our results demonstrate that TAT has potential for use in portable, cost-effective imagers for pediatric brains.

  20. 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.

  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. 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.

  3. Direct demonstration of retroviral recombination in a rhesus monkey.

    PubMed Central

    Wooley, D P; Smith, R A; Czajak, S; Desrosiers, R C

    1997-01-01

    Recombination may be an important mechanism for increasing variation in retroviral populations. Retroviral recombination has been demonstrated in tissue culture systems by artificially creating doubly infected cells. Evidence for retroviral recombination in vivo is indirect and is based principally on the identification of apparently mosaic human immunodeficiency virus type 1 genomes from phylogenetic analyses of viral sequences. We infected a rhesus monkey with two different molecularly cloned strains of simian immunodeficiency virus. One strain of virus had a deletion in vpx and vpr, and the other strain had a deletion in nef. Each strain on its own induced low virus loads and was nonpathogenic in rhesus monkeys. When injected simultaneously into separate legs of the same monkey, persistent high virus loads and declines in CD4+ lymphocyte concentrations were observed. Analysis of proviral DNA isolated directly from peripheral blood mononuclear cells showed that full-length, nondeleted SIVmac239 predominated by 2 weeks after infection. These results provide direct experimental evidence for genetic recombination between two different retroviral strains in an infected host. The results illustrate the ease and rapidity with which recombination can occur in an infected animal and the selection that can occur for variants generated by genetic recombination. PMID:9371629

  4. 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.

  5. 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.

  6. 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.

  7. 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

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

    PubMed

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

    2007-09-01

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

  9. 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.

  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. [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.

  12. Pathology of Lassa virus infection in the rhesus monkey.

    PubMed

    Callis, R T; Jahrling, P B; DePaoli, A

    1982-09-01

    The clinical signs and gross and microscopic lesions of Lassa virus infection in the rhesus monkey are described. Of 17 monkeys infected with Lassa virus, nine died or were killed when moribund. The clinical signs were lethargy, aphagia, constipation, fever, conjunctivitis, and skin rash. Pulmonary congestion, pleural effusion, pericardial edema, hydropericardium, and a few visceral hemorrhages were present grossly. Major microscopic lesions were necrotizing hepatitis and interstitial pneumonia. Other microscopic changes were present in the heart, small intestine, spleen, lymph nodes, kidney, urinary bladder, adrenal glands, and central nervous system; however, most of these lesions were mild. In fact, death could not always be attributed to the morphologic changes; therefore, function alterations must be examined.

  13. Sedative effects of intranasal oxytocin in rabbits and rhesus monkeys.

    PubMed

    Hess, L; Votava, M; Málek, J; Kurzová, A; Slíva, J

    2016-12-21

    Oxytocin is a hormone therapeutically used mainly for its peripheral effects during pregnancy in the uterus and breasts. However, additional central effects, i.e. anxiolytic effect, decreased level of social stress and increased empathy have been also observed. Hence, the aim of our study was to evaluate if nasal oxytocin can be used as anxiolytic substance in rhesus monkeys (n=20) and rabbits (n=20). Simultaneously, mean arterial blood pressure, arterial oxygen saturation of hemoglobin and pulse rate were monitored in all the evaluated animals. While rabbits lost righting reflex, monkeys developed a dose-dependent loss of aggressiveness and/or anxiety as evaluated by behavioral methods (aggressive behavior was classified as non-sedated - sedated - strongly sedated).

  14. Caloric restriction improves health and survival of rhesus monkeys

    PubMed Central

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

    2017-01-01

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

  15. 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

  16. 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

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

    PubMed Central

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

    2009-01-01

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

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

    PubMed

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

    2009-07-15

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

  19. Vocal-Tract Resonances as Indexical Cues in Rhesus Monkeys

    PubMed Central

    Ghazanfar, Asif A.; Turesson, Hjalmar K.; Maier, Joost X.; van Dinther, Ralph; Patterson, Roy D.; Logothetis, Nikos K.

    2007-01-01

    Summary Vocal-tract resonances (or formants) are acoustic signatures in the voice and are related to the shape and length of the vocal tract. Formants play an important role in human communication, helping us not only to distinguish several different speech sounds [1], but also to extract important information related to the physical characteristics of the speaker, so-called indexical cues. How did formants come to play such an important role in human vocal communication? One hypothesis suggests that the ancestral role of formant perception—a role that might be present in extant nonhuman primates—was to provide indexical cues [2–5]. Although formants are present in the acoustic structure of vowel-like calls of monkeys [3–8] and implicated in the discrimination of call types [8–10], it is not known whether they use this feature to extract indexical cues. Here, we investigate whether rhesus monkeys can use the formant structure in their “coo” calls to assess the age-related body size of conspecifics. Using a preferential-looking paradigm [11, 12] and synthetic coo calls in which formant structure simulated an adult/large- or juvenile/small-sounding individual, we demonstrate that untrained monkeys attend to formant cues and link large-sounding coos to large faces and small-sounding coos to small faces—in essence, they can, like humans [13], use formants as indicators of age-related body size. PMID:17320389

  20. Unconstrained three-dimensional reaching in rhesus monkeys.

    PubMed

    Jindrich, Devin L; Courtine, Gregoire; Liu, James J; McKay, Heather L; Moseanko, Rod; Bernot, Timothy J; Roy, Roland R; Zhong, Hui; Tuszynski, Mark H; Reggie Edgerton, V

    2011-03-01

    To better understand normative behavior for quantitative evaluation of motor recovery after injury, we studied arm movements by non-injured rhesus monkeys during a food-retrieval task. While seated, monkeys reached, grasped, and retrieved food items. We recorded three-dimensional kinematics and muscle activity, and used inverse dynamics to calculate joint moments due to gravity, segmental interactions, and to the muscles and tissues of the arm. Endpoint paths showed curvature in three dimensions, suggesting that maintaining straight paths was not an important constraint. Joint moments were dominated by gravity. Generalized muscle and interaction moments were less than half of the gravitational moments. The relationships between shoulder and elbow resultant moments were linear during both reach and retrieval. Although both reach and retrieval required elbow flexor moments, an elbow extensor (triceps brachii) was active during both phases. Antagonistic muscles of both the elbow and hand were co-activated during reach and retrieval. Joint behavior could be described by lumped-parameter models analogous to torsional springs at the joints. Minor alterations to joint quasi-stiffness properties, aided by interaction moments, result in reciprocal movements that evolve under the influence of gravity. The strategies identified in monkeys to reach, grasp, and retrieve items will allow the quantification of prehension during recovery after a spinal cord injury and the effectiveness of therapeutic interventions.

  1. 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.

  2. 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.

  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. Lassa Virus Infection of Rhesus Monkeys: Pathogenesis and Treatment with Ribavirin

    DTIC Science & Technology

    1980-05-01

    viruses [5, 61, is effective in treating severe The views of the authors do not purport to reflect the posi- Lassa virus disease in rhesus monkeys...THE JOURNAL OF INFECTIOUS DISEASES - VOL. 141, NO. 5 MAY 1980 1980 by The University of Chicago. 0022-1899/80/410500 .95 ECr C- Lassa Virus Infection...Atlanta, Georgia Rhesus monkeys were experimentally infected with Lassa virus to establish their suita- bility as a nonhuman primate model for the human

  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. 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.

  7. 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

  8. Rapid Inflammasome Activation following Mucosal SIV Infection of Rhesus Monkeys.

    PubMed

    Barouch, Dan H; Ghneim, Khader; Bosche, William J; Li, Yuan; Berkemeier, Brian; Hull, Michael; Bhattacharyya, Sanghamitra; Cameron, Mark; Liu, Jinyan; Smith, Kaitlin; Borducchi, Erica; Cabral, Crystal; Peter, Lauren; Brinkman, Amanda; Shetty, Mayuri; Li, Hualin; Gittens, Courtney; Baker, Chantelle; Wagner, Wendeline; Lewis, Mark G; Colantonio, Arnaud; Kang, Hyung-Joo; Li, Wenjun; Lifson, Jeffrey D; Piatak, Michael; Sekaly, Rafick-Pierre

    2016-04-21

    The earliest events following mucosal HIV-1 infection, prior to measurable viremia, remain poorly understood. Here, by detailed necropsy studies, we show that the virus can rapidly disseminate following mucosal SIV infection of rhesus monkeys and trigger components of the inflammasome, both at the site of inoculation and at early sites of distal virus spread. By 24 hr following inoculation, a proinflammatory signature that lacked antiviral restriction factors was observed in viral RNA-positive tissues. The early innate response included expression of NLRX1, which inhibits antiviral responses, and activation of the TGF-β pathway, which negatively regulates adaptive immune responses. These data suggest a model in which the virus triggers specific host mechanisms that suppress the generation of antiviral innate and adaptive immune responses in the first few days of infection, thus facilitating its own replication. These findings have important implications for the development of vaccines and other strategies to prevent infection.

  9. Evaluation of rhesus monkey and guinea pig hepatic cytosol fractions as models for human aldehyde oxidase.

    PubMed

    Choughule, Kanika V; Barr, John T; Jones, Jeffrey P

    2013-10-01

    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.

  10. 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

  11. Natural infection with canine distemper virus in hand-feeding Rhesus monkeys in China.

    PubMed

    Sun, Zhaozeng; Li, Aixue; Ye, Huahu; Shi, Yansheng; Hu, Zhongming; Zeng, Lin

    2010-03-24

    An outbreak of canine distemper virus (CDV) in hand-feeding Rhesus monkeys in China was reported. Twenty Rhesus monkeys presented blood and mucus in feces, respiratory symptoms, anorexia, acute fever, thicken of footpad and red rashes in the faces over 1-month period. CDV infection was identified by characteristic clinical signs, the specific detection of the BIT Rapid color CDV detection kit, electron microscopy and the results of sequence aligning. A phylogenetic analysis further confirmed that the CDV in the Rhesus monkeys belonged to the clade of the epidemic CDV types of China. All the infected monkeys were monitored and treated with antiserum therapy. The antiserum therapy seemed more effective for adult monkeys than young monkeys. Twelve monkeys died. The high mortality might indicate that the virulence of CDV to monkeys was enhanced. This is the first report we are aware of documenting Rhesus monkeys infected with CDV in China. Urgent work should be done to prevent the possibly epidemic of CDV in non-human primate.

  12. 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.

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

    PubMed

    Guderian, Sebastian; Brigham, Danielle; Mishkin, Mortimer

    2011-11-29

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

  14. 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.

  15. 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.

  16. 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.

  17. 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…

  18. 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…

  19. Tissue Specificity of Decellularized Rhesus Monkey Kidney and Lung Scaffolds

    PubMed Central

    Nakayama, Karina H.; Lee, C. Chang I.; Batchelder, Cynthia A.; Tarantal, Alice F.

    2013-01-01

    Initial steps in establishing an optimal strategy for functional bioengineered tissues is generation of three-dimensional constructs containing cells with the appropriate organization and phenotype. To effectively utilize rhesus monkey decellularized kidney scaffolds, these studies evaluated two key parameters: (1) residual scaffold components after decellularization including proteomics analysis, and (2) the use of undifferentiated human embryonic stem cells (hESCs) for recellularization in order to explore cellular differentiation in a tissue-specific manner. Sections of kidney and lung were selected for a comparative evaluation because of their similar pattern of organogenesis. Proteomics analysis revealed the presence of growth factors and antimicrobial proteins as well as stress proteins and complement components. Immunohistochemistry of recellularized kidney scaffolds showed the generation of Cytokeratin+ epithelial tubule phenotypes throughout the scaffold that demonstrated a statistically significant increase in expression of kidney-associated genes compared to baseline hESC gene expression. Recellularization of lung scaffolds showed that cells lined the alveolar spaces and demonstrated statistically significant upregulation of key lung-associated genes. However, overall expression of kidney and lung-associated markers was not statistically different when the kidney and lung recellularized scaffolds were compared. These results suggest that decellularized scaffolds have an intrinsic spatial ability to influence hESC differentiation by physically shaping cells into tissue-appropriate structures and phenotypes, and that additional approaches may be needed to ensure consistent recellularization throughout the matrix. PMID:23717553

  20. 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.

  1. Rhesus monkey neural stem cell transplantation promotes neural regeneration in rats with hippocampal lesions.

    PubMed

    Ye, Li-Juan; Bian, Hui; Fan, Yao-Dong; Wang, Zheng-Bo; Yu, Hua-Lin; Ma, Yuan-Ye; Chen, Feng

    2016-09-01

    Rhesus monkey neural stem cells are capable of differentiating into neurons and glial cells. Therefore, neural stem cell transplantation can be used to promote functional recovery of the nervous system. Rhesus monkey neural stem cells (1 × 10(5) cells/μL) were injected into bilateral hippocampi of rats with hippocampal lesions. Confocal laser scanning microscopy demonstrated that green fluorescent protein-labeled transplanted cells survived and grew well. Transplanted cells were detected at the lesion site, but also in the nerve fiber-rich region of the cerebral cortex and corpus callosum. Some transplanted cells differentiated into neurons and glial cells clustering along the ventricular wall, and integrated into the recipient brain. Behavioral tests revealed that spatial learning and memory ability improved, indicating that rhesus monkey neural stem cells noticeably improve spatial learning and memory abilities in rats with hippocampal lesions.

  2. [A technique of rhesus monkey neural progenitor cells intravitreal transplant to rats].

    PubMed

    Bian, Hui; Fan, Yao-Dong; Guo, Li-Yun; Yu, Hua-Lin

    2012-02-01

    To investigate a simple and effective intraocular xenotransplant technique of rhesus monkey neural progenitor cells to rats, mechanical injury was induced in the rat's right retina. And the GFP-labeled rhesus monkey neural progenitor cells suspension was slowly injected into the vitreous space of the right injured and left control eye. Confocal image suggested that the xenografted cells survived in both the injured and control eye, meanwhile the cells integrated in the injured right retina. The results demonstrated that intravitreal xenotransplant could be adopted as a simple and reliable method.

  3. 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.

  4. Failure of intravenous pentagastrin challenge to induce panic-like effects in rhesus monkeys.

    PubMed

    Rupniak, N M; Schaffer, L; Siegl, P; Iversen, S D

    1993-08-01

    We examined the ability of intravenous (i.v.) challenge with pentagastrin to induce behavioural and cardiovascular effects consistent with panic attack in conscious rhesus monkeys. For behavioural evaluation, 4 naive male rhesus monkeys familiar with minimal manual restraint necessary for drug administration received a rapid i.v. bolus of pentagastrin (4, 8 or 16 micrograms/kg) or water on four separate occasions according to a randomised cross-over design. Behaviour was rated by a blind observer continuously during, and for the first 5 min immediately following i.v. injections while the monkey sat on the handler's lap, and then for a further 25 min in an individual observation cage. In separate experiments, the ability of pentagastrin to alter cardiovascular parameters which may accompany panic or anxiety (elevated heart rate and blood pressure) was explored. For cardiovascular studies, 8 male or female rhesus monkeys with femoral artery catheters were chair restrained and received a bolus injection of pentagastrin (4, 8 or 16 micrograms/kg) or saline into the saphenous vein at 30 min intervals. Blood pressure and heart rate were monitored continuously using a Statham Gould pressure transducer. Pentagastrin induced no consistent behavioural or cardiovascular changes. Similar pilot studies using CCK4 also failed to reveal such effects. We conclude that CCK-induced panic-like effects may not be demonstrable following challenge with pentagastrin under laboratory conditions in rhesus monkeys.

  5. 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.

  6. 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

    2016-09-09

    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.

  7. Protective Efficacy of Multiple Vaccine Platforms Against Zika Virus Challenge in Rhesus Monkeys

    PubMed Central

    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.

    2017-01-01

    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 conferred passive protection in adoptive transfer studies. A plasmid DNA vaccine and a single-shot recombinant rhesus adenovirus serotype 52 vector expressing ZIKV prM-Env 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

  8. Selection and Pairing of ’Normal’ Rhesus Monkeys (Macaca mulatta) for Research.

    DTIC Science & Technology

    1978-11-08

    os. Black arrows outline gall blciddr.Wiearwndctspiio ofrgtaboia oaiy 10• V.. b:k The absence of reports or mention of spontaneous urolithiasis in the...literature indicates that this entity is rare in rhesus monkeys. A case report of urolithiasis in one Macaca cyclopis monkey and a literature review...intravenous pyelography, cholelithiasis and urolithiasis were deleted as possible causes of the opacities. It is possible that these dense objects

  9. 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.

  10. A draft map of rhesus monkey tissue proteome for biomedical research.

    PubMed

    Lee, Jin-Gyun; McKinney, Kimberly Q; Lee, Yong-Yook; Chung, Hae-Na; Pavlopoulos, Antonis J; Jung, Kook Y; Kim, Woong-Ki; Kuroda, Marcelo J; Han, David K; Hwang, Sunil

    2015-01-01

    Though the rhesus monkey is one of the most valuable non-human primate animal models for various human diseases because of its manageable size and genetic and proteomic similarities with humans, proteomic research using rhesus monkeys still remains challenging due to the lack of a complete protein sequence database and effective strategy. To investigate the most effective and high-throughput proteomic strategy, comparative data analysis was performed employing various protein databases and search engines. The UniProt databases of monkey, human, bovine, rat and mouse were used for the comparative analysis and also a universal database with all protein sequences from all available species was tested. At the same time, de novo sequencing was compared to the SEQUEST search algorithm to identify an optimal work flow for monkey proteomics. Employing the most effective strategy, proteomic profiling of monkey organs identified 3,481 proteins at 0.5% FDR from 9 male and 10 female tissues in an automated, high-throughput manner. Data are available via ProteomeXchange with identifier PXD001972. Based on the success of this alternative interpretation of MS data, the list of proteins identified from 12 organs of male and female subjects will benefit future rhesus monkey proteome research.

  11. 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.

  12. 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.

  13. 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…

  14. 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…

  15. 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…

  16. 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…

  17. 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…

  18. 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…

  19. 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…

  20. 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…

  1. 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…

  2. 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.

  3. The Metabolic and Thermoregulatory Responses of Rhesus Monkeys to Combined Exercise and Environmental Heat Load

    DTIC Science & Technology

    1993-08-01

    P.T. Wall and F. Sato. In vivo and in vitro characteristics of eccrine sweating in patas and rhesus monkeys. J. Appl. Physiol.: Respirat. Environ...in monkeys. Am. J. Physiol. 245: R76-R82, 1983. 15. Gisolfi, C.V., K. Sato and P.T. Wall. Monkey model and techniques for studying eccrine sweating in...baboon. J. Appl. Physiol. 55: 1173-1177, 1983. 18. Johnson, G.S. and R.S. Elizondo. Eccrine sweat gland in Macaca mulatta: physiology, histochemistry

  4. 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

  5. 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.

  6. 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.

  7. Characterization and presumptive identification of Helicobacter pylori isolates from rhesus monkeys.

    PubMed Central

    Drazek, E S; Dubois, A; Holmes, R K

    1994-01-01

    We characterized 38 Helicobacter isolates, including 22 from gastric biopsy samples obtained from 14 rhesus monkeys and single isolates from 16 monkeys in a different colony. Biochemical profiles of these isolates were nearly identical to that of Helicobacter pylori ATCC 43504. Restriction fragment length polymorphism (RFLP) analysis indicated that each infected monkey harbored one to four strains. The 17 RFLP types found among these 22 isolates differed from all seven RFLPs found among the other 16 isolates. Thus, monkeys within a given colony are more likely to be infected by Helicobacter isolates with the same or a similar RFLP than are monkeys from different colonies. A 16S rRNA gene was amplified by PCR and cloned from the Helicobacter isolate from rhesus monkey 85D08. Ribotyping with this probe demonstrated less diversity among isolates from rhesus monkeys than was reported among isolates of H. pylori from humans, as did RFLP analysis of a PCR fragment of the ureA-ureB gene cluster. The DNA sequence of the cloned 16S rRNA gene was determined and compared with sequences reported for H. pylori and other Helicobacter species. Our analysis of 127 nucleotides (corresponding with residues 1240 to 1366 of the Escherichia coli 16S rRNA gene) indicated that the Helicobacter isolate from monkey 85D08 was 99.2 to 100% homologous to isolates of H. pylori from humans but only 83.5 to 96.9% homologous with other Helicobacter species in this region of the 16S rRNA gene. These data provide strong support for the presumptive identification of these isolates as H. pylori. Images PMID:7523441

  8. Exploring a partially enclosed space by lead-exposed female rhesus monkeys.

    PubMed

    Lasky, R E; Laughlin, N K

    2001-01-01

    Beginning on Day 8 postpartum, lead acetate was administered to female rhesus monkeys (n=48). Their blood lead levels rose to 35-40 microg/dl (the level maintained for the duration of the study period) by 12 weeks of age. Weekly, these lead-exposed monkeys and their controls (n=23) were placed in a partially enclosed space from the second postnatal week until they escaped three times or were 26 weeks old. The lead-exposed monkeys exhibited more fear, were more likely to be agitated, and climbed more frequently during the first testing session. In subsequent sessions, they more frequently explored the periphery of the test area than the controls. The lead-exposed monkeys also tended to escape sooner although that trend did not consistently reach the.05 level of significance. The increased activity and agitation of the lead-exposed monkeys is suggestive of deficits reported in human children with high blood lead levels.

  9. A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys

    PubMed Central

    Dai, PeiMin; Huang, Hui; Zhang, Lin; He, Jing; Zhao, XuDong; Yang, FuHan; Zhao, Ning; Yang, JianZhen; Ge, LongJiao; Lin, Yu; Yu, HuaLin; Wang, JianHong

    2017-01-01

    Endothelin-1 (ET-1), a vasoconstrictor, has recently been used to induce focal ischemia in rodents and marmoset monkeys. The rhesus monkey, however, has numerous advantages to the rodent and marmoset that make it a superior and irreplaceable animal model for studying stroke in the brain. In the present study, after mapping the preferred hand representation in two healthy male monkeys with intracortical micro-stimulation, ET-1 was microinjected into the contralateral motor cortex (M1) to its preferred hand. The monkeys had been trained in three manual dexterity tasks before the microinjection and were tested for these tasks following the ET-1 injection. Brain Magnetic Resonance Imaging scans were performed 1, 7, 14 and 28 days post ischemia. It was found that ET-1 impaired the manual dexterity of the monkeys in the vertical slot and rotating Brinkman board tasks 3–8 days after the injection. Brain imaging found that severe edema was present 7 days after the focal ischemia. This data suggest that ET-1 can induce transient ischemic stroke in rhesus monkey and that ET-1 induced focal ischemia in non-human primates is a potential model to study the mechanism of stroke and brain repair after stroke. PMID:28358140

  10. A pilot study on transient ischemic stroke induced with endothelin-1 in the rhesus monkeys.

    PubMed

    Dai, PeiMin; Huang, Hui; Zhang, Lin; He, Jing; Zhao, XuDong; Yang, FuHan; Zhao, Ning; Yang, JianZhen; Ge, LongJiao; Lin, Yu; Yu, HuaLin; Wang, JianHong

    2017-03-30

    Endothelin-1 (ET-1), a vasoconstrictor, has recently been used to induce focal ischemia in rodents and marmoset monkeys. The rhesus monkey, however, has numerous advantages to the rodent and marmoset that make it a superior and irreplaceable animal model for studying stroke in the brain. In the present study, after mapping the preferred hand representation in two healthy male monkeys with intracortical micro-stimulation, ET-1 was microinjected into the contralateral motor cortex (M1) to its preferred hand. The monkeys had been trained in three manual dexterity tasks before the microinjection and were tested for these tasks following the ET-1 injection. Brain Magnetic Resonance Imaging scans were performed 1, 7, 14 and 28 days post ischemia. It was found that ET-1 impaired the manual dexterity of the monkeys in the vertical slot and rotating Brinkman board tasks 3-8 days after the injection. Brain imaging found that severe edema was present 7 days after the focal ischemia. This data suggest that ET-1 can induce transient ischemic stroke in rhesus monkey and that ET-1 induced focal ischemia in non-human primates is a potential model to study the mechanism of stroke and brain repair after stroke.

  11. Effect of substrates on the mechanical performance of rhesus monkey papillary muscle.

    PubMed

    Snow, T R

    1980-04-15

    This study examines the effect of different substrates on mechanical performance of excised papillary muscles from rhesus monkeys which had been divided into a control group and an experimental group fed a high fat diet for 5 months prior to sacrifice. The results show that performance is affected by availabel substrate for both groups. The performance of the experimental group was depressed relative to control with the short chain fatty acid, butyrate (C4), producing a monotonically decreasing force-frequency response. Relative to the other mammals, isolated rhesus papillary muscles exhibited a protracted treppe which was sensitive to beta-adrenergic blockade with propranolol.

  12. 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.

  13. Simian immunodeficiency virus mutants resistant to serum neutralization arise during persistent infection of rhesus monkeys.

    PubMed Central

    Burns, D P; Collignon, C; Desrosiers, R C

    1993-01-01

    We previously described the pattern of sequence variation in gp120 following persistent infection of rhesus monkeys with the pathogenic simian immunodeficiency virus SIVmac239 molecular clone (D.P.W. Burns and R.C. Desrosiers, J. Virol. 65:1843, 1991). Sequence changes were confined largely to five variable regions (V1 to V5), four of which correspond to human immunodeficiency virus type 1 (HIV-1) gp120 variable regions. Remarkably, 182 of 186 nucleotide substitutions that were documented in these variable regions resulted in amino acid changes. This is an extremely nonrandom pattern, which suggests selective pressure driving amino acid changes in discrete variable domains. In the present study, we investigated whether neutralizing-antibody responses are one selective force responsible at least in part for the observed pattern of sequence variation. Variant env sequences called 1-12 and 8-22 obtained 69 and 93 weeks after infection of a rhesus monkey with cloned SIVmac239 were recombined into the parental SIVmac239 genome, and variant viruses were generated by transfection of cultured cells with cloned DNA. The 1-12 and 8-22 recombinants differ from the parental SIVmac239 at 18 amino acid positions in gp120 and at 5 and 10 amino acid positions, respectively, in gp41. Sequential sera from the monkey infected with cloned SIVmac239 from which the 1-12 and 8-22 variants were isolated showed much higher neutralizing antibody titers to cloned SIVmac239 than to the cloned 1-12 and 8-22 variants. For example, at 55 weeks postinfection the neutralizing antibody titer against SIVmac239 was 640 while those to the variant viruses were 40 and less than 20. Two other rhesus monkeys infected with cloned SIVmac239 showed a similar pattern. Rhesus monkeys were also experimentally infected with the cloned variants so that the type-specific nature of the neutralizing antibody responses could be verified. Indeed, each of these monkeys showed neutralizing-antibody responses of much

  14. Lassa virus infection of rhesus monkeys: pathogenesis and treatment with ribavirin.

    PubMed

    Jahrling, P B; Hesse, R A; Eddy, G A; Johnson, K M; Callis, R T; Stephen, E L

    1980-05-01

    Rhesus monkeys were experimentally infected with Lassa virus to establish their suitability as a nonhuman primate model for the human disease and to test the protective efficacy of ribavirin, an antiviral drug. Six of 10 untreated control monkeys died after subcutaneous inoculation of 10(6.1) plaque-forming units of Lassa virus (strain Josiah). Infectivity titrations of tissue homogenates from the six dead monkeys indicated significant replication in all tissues tested except the central nervous system. This distribution of virus was confirmed by direct immunofluorescence examination of cryostat-sectioned tissues. Ribavirin was beneficial in the treatment of two groups of infected monkeys. Four monkeys first treated on the day of viral inoculation experienced only mild clinical disease; four monkeys first treated five days later experienced a more severe illness. None of the eight monkeys treated with ribavirin died. Viremia titers and elevations of levels of serum transaminases in treated monkeys were significantly lower than in controls. Ribavirin may be beneficial in the treatment of humans exposed to this life-threatening virus.

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

    PubMed

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

    2017-02-01

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

  16. Predicting rhesus monkey eye movements during natural-image search.

    PubMed

    Segraves, Mark A; Kuo, Emory; Caddigan, Sara; Berthiaume, Emily A; Kording, Konrad P

    2017-03-01

    There are three prominent factors that can predict human visual-search behavior in natural scenes: the distinctiveness of a location (salience), similarity to the target (relevance), and features of the environment that predict where the object might be (context). We do not currently know how well these factors are able to predict macaque visual search, which matters because it is arguably the most popular model for asking how the brain controls eye movements. Here we trained monkeys to perform the pedestrian search task previously used for human subjects. Salience, relevance, and context models were all predictive of monkey eye fixations and jointly about as precise as for humans. We attempted to disrupt the influence of scene context on search by testing the monkeys with an inverted set of the same images. Surprisingly, the monkeys were able to locate the pedestrian at a rate similar to that for upright images. The best predictions of monkey fixations in searching inverted images were obtained by rotating the results of the model predictions for the original image. The fact that the same models can predict human and monkey search behavior suggests that the monkey can be used as a good model for understanding how the human brain enables natural-scene search.

  17. Predicting rhesus monkey eye movements during natural-image search

    PubMed Central

    Segraves, Mark A.; Kuo, Emory; Caddigan, Sara; Berthiaume, Emily A.; Kording, Konrad P.

    2017-01-01

    There are three prominent factors that can predict human visual-search behavior in natural scenes: the distinctiveness of a location (salience), similarity to the target (relevance), and features of the environment that predict where the object might be (context). We do not currently know how well these factors are able to predict macaque visual search, which matters because it is arguably the most popular model for asking how the brain controls eye movements. Here we trained monkeys to perform the pedestrian search task previously used for human subjects. Salience, relevance, and context models were all predictive of monkey eye fixations and jointly about as precise as for humans. We attempted to disrupt the influence of scene context on search by testing the monkeys with an inverted set of the same images. Surprisingly, the monkeys were able to locate the pedestrian at a rate similar to that for upright images. The best predictions of monkey fixations in searching inverted images were obtained by rotating the results of the model predictions for the original image. The fact that the same models can predict human and monkey search behavior suggests that the monkey can be used as a good model for understanding how the human brain enables natural-scene search. PMID:28355625

  18. A preliminary report on oral fat tolerance test in rhesus monkeys

    PubMed Central

    2014-01-01

    Background Oral fat tolerance test (OFTT) has been widely used to assess the postprandial lipemia in human beings, but there is few studies concerning OFTT in nonhuman primates. This study is designed to explore the feasibility of OFTT in rhesus monkeys. Methods In a cross-over study, a total of 8 adult female rhesus monkeys were fed with normal monkey diet (NND), high sugar high fat diet (HHD), and extremely high fat diet (EHD), respectively. Each monkey consumed NND, HHD and EHD respectively, each weighing 60 g. Serial blood samples were collected at 1, 2, 3, 4, 5, and 6 h after ingesting each kind of food. Triglyceride, cholesterol, glucose, and insulin at each time point were measured. The area under the curve of triglyceride (TG-AUC) and triglyceride peak response (TG-PR) were also calculated. Results All monkeys ingested 3 kinds of foods within 15 minutes. TG-AUC and TG-PR of HHD group were higher than those of the other two groups. Postprandial triglyceride levels at 2, 3, 4, and 5 hours in HHD group during OFTT were also higher than those in NND and EHD group. Conclusions HHD diet can be used in OFTT for nonhuman primates. PMID:24410972

  19. 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.

  20. Changes in the gaze fixation reaction in rhesus monkeys during the initial stage of water immersion.

    PubMed

    Eron, Julia N; Miller, Natalia V; Badakva, Anatoly M

    2004-07-01

    The gaze fixation reaction was studied in three rhesus monkeys before and during thermoneutral (34.5 degrees C) water immersion to the mid-chest level. The angular vestibulo-ocular reflex gain increased and the head angular velocity decreased significantly in all monkeys in 5 h after the start of immersion. Additionally, one animal was immersed to the neck level. Two hours in the condition of more pronounced support deprivation decreased significantly angular velocity of the head but not increased the angular vestibulo-ocular reflex gain. Therefore, support deprivation act upon the head movement control first.

  1. 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.

  2. 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.

  3. 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…

  4. A Finite Element Analysis of the Creep Response of Lumbar Intervertebral Joints in the Rhesus Monkey.

    DTIC Science & Technology

    1982-12-01

    description of the intervertebral joint. The Rhesus Monkey spine is a complex structure composed of a number of mobile vertebrae. It is divided into 4 reg...IS. -SUPPLEMENTARY NOTES 8o:it~Ics A ~JA~q Air. Force insItit of Tehnology (ATCJ 1 9 J N ’ Wrgb-o:.-o.,&O 43 19. KEY WORDS (Continue on reverse side

  5. Persistent fear responses in rhesus monkeys to the optical stimulus of "looming".

    PubMed

    SCHIFF, W; CAVINESS, J A; GIBSON, J J

    1962-06-15

    The approach of an object corresponds with a spatiotemporal optical stimulus consisting of a symmetrical expansion of a closed contour in the field of view. The visual equivalent of impending collision was isolated and compared with its sequential inversion. Infant and adult rhesus monkeys manifested persistent avoidance responses to "looming" but not to the inverse. This visual stimulus alone is a strong exciter of avoidance, and the response appears early in life.

  6. 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

  7. An alternative method of chronic cerebrospinal fluid collection via the cisterna magna in conscious rhesus monkeys.

    PubMed

    Gilberto, David B; Zeoli, Angela H; Szczerba, Peter J; Gehret, John R; Holahan, Marie A; Sitko, Gary R; Johnson, Colena A; Cook, Jacquelynn J; Motzel, Sherri L

    2003-07-01

    Models of chronic cerebrospinal fluid (CSF) collection previously have been established for nonhuman primates and canines; many of these methods implement stainless-steel cannulas into the lateral or 4th ventricles or catheters into the cerebral or spinal subarachnoid space. These models have proved successful and reliable but unfortunately require invasive techniques to pass through the skull or require a laminectomy to enter the spinal subarachnoid space, involve the use of expensive and highly specialized stereotaxic equipment for the precise placement of the implants, and may require exteriorized hardware which is cumbersome to maintain and unaesthetic. The model we developed for the rhesus monkey allows for direct access to CSF outflow from the cisterna magna by using a 3.5-French fenestrated silicone catheter which was placed 1.0 cm into the cisterna. The catheter was attached to a titanium port placed subcutaneously between the scapulae to permit easy access for sampling CSF in a conscious, chaired rhesus monkey. We currently have instrumented animals from which we have consistently collected CSF for over 18 months. This novel, economical, less-invasive method permits chronic, reliable collection of CSF in conscious rhesus monkeys and has the additional advantages that the model is easier to maintain and more aesthetic.

  8. 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.

  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. Huperzine A: Behavioral and Pharmacological Evaluation in Rhesus Monkeys

    DTIC Science & Technology

    2008-06-01

    U.S. Army Medical Research Institute of Chemical Defense USAMRICD-TR-08-05 Huperzine A: Behavioral and Pharmacological Evaluation in Rhesus...public release; distribution unlimited U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, MD 21010-5400...experimental protocol was approved by the Animal Care and Use Committee at the United States Army Medical Research Institute of Chemical Defense and

  11. Social Facilitation of Cognition in Rhesus Monkeys: Audience Vs. Coaction.

    PubMed

    Reynaud, Amélie J; Guedj, Carole; Hadj-Bouziane, Fadila; Meunier, Martine; Monfardini, Elisabetta

    2015-01-01

    Social psychology has long established that the mere presence of a conspecific, be it an active co-performer (coaction effect), or a passive spectator (audience effect) changes behavior in humans. Yet, the process mediating this fundamental social influence has so far eluded us. Brain research and its nonhuman primate animal model, the rhesus macaque, could shed new light on this long debated issue. For this approach to be fruitful, however, we need to improve our patchy knowledge about social presence influence in rhesus macaques. Here, seven adults (two dyads and one triad) performed a simple cognitive task consisting in touching images to obtain food treats, alone vs. in presence of a co-performer or a spectator. As in humans, audience sufficed to enhance performance to the same magnitude as coaction. Effect sizes were however four times larger than those typically reported in humans in similar tasks. Both findings are an encouragement to pursue brain and behavior research in the rhesus macaque to help solve the riddle of social facilitation mechanisms.

  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

    2014-08-07

    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. Reversal of testicular function after prolonged suppression with an LHRH agonist in rhesus monkeys.

    PubMed

    Sundaram, K; Keizer-Zucker, A; Thau, R B; Bardin, C W

    1987-01-01

    Using subcutaneously implanted osmotic pumps, four male rhesus monkeys were continuously infused for 18 months with 100 micrograms/day of [(imBzl)-D-His6-Pro9-NEt]-LHRH (LHRH-A), a potent agonist of LHRH. After an initial increase, serum testosterone levels declined to 10% of pretreatment levels in three monkeys and the response to electroejaculation was lost. There was a decrease in testicular volume. Androgen replacement in the form of subcutaneous SILASTIC implants releasing 7 alpha-methyl-19-nor-testosterone acetate led to a restoration of ejaculatory response and the electroejaculates were devoid of spermatozoa. Under this treatment regimen (100 micrograms LHRH-A + 100 micrograms androgen daily), azoospermia was essentially maintained in the three monkeys for about 8 months. Withdrawal of LHRH-A and androgen treatment led to a complete restoration of testicular function. Serum testosterone returned to control levels and spermatozoa reappeared in the ejaculates with sperm counts reaching the normal range. Testicular volumes showed a gradual increase. These results indicate that continuous administration of an LHRH agonist together with an androgen can induce an extended period of azoospermia in rhesus monkeys. These results also show that after prolonged suppression (more than one year) of testicular function complete recovery occurs after cessation of treatment.

  14. Pharmacokinetics of Oxymorphone in Titi Monkeys (Callicebus spp.) and Rhesus Macaques (Macaca mulatta)

    PubMed Central

    Kelly, Kristi R; Pypendop, Bruno H; Grayson, J Kevin; Stanley, Scott D; Christe, Kari L; Summers, Laura M; Lerche, Nicholas W

    2011-01-01

    Oxymorphone is a pure μ-opioid receptor agonist that is commonly used in nonhuman primate medicine and surgery to minimize pain ranging in intensity from moderate to severe. We compared pharmacokinetic profiles and physiologic and behavioral responses to oxymorphone between titi monkeys (Callicebus spp.) and rhesus macaques (Macaca mulatta). Titi monkeys (n = 4) and rhesus macaques (n = 4) were injected intravenously with either a bolus of 0.075 mg/kg oxymorphone or placebo on multiple occasions, with a minimal washout period of 14 d between trials. Blood collection was limited to no more than 3 samples per trial, with samples collected at multiple time points until 10 h after injection. Collection periods, animal order, and testing day were randomized. In addition, macaques underwent a single serial collection at all time points to validate study design. A 2-compartment model best described the disposition of oxymorphone in both species. Clearance was faster in macaques than titi monkeys, in which terminal half-life was longer. Statistically significant physiologic differences were found between species and between treatments within species. Apart from these effects, oxymorphone did not significantly change physiologic parameters over time. After oxymorphone treatment, macaques demonstrated behaviors reflecting pruritis, whereas titi monkeys exhibited sedation. Despite its mild side effects, we recommend the consideration of oxymorphone for pain management protocols in both Old and New World nonhuman primates. PMID:21439215

  15. In vivo evaluation of optic nerve aging in adult rhesus monkey by diffusion tensor imaging

    PubMed Central

    Yan, Yumei; Li, Longchuan; Preuss, Todd M.; Hu, Xiaoping; Herndon, James G.

    2014-01-01

    Aging of the optic nerve can result in reduced visual sensitivity or vision loss. Normal optic nerve aging has been investigated previously in tissue specimens but poorly explored in vivo. In the present study, the normal aging of optic nerve was evaluated by diffusion tensor imaging (DTI) in non-human primates. Adult female rhesus monkeys at the ages of 9 to 13 years old (young group, n=8) and 21 to 27 years old (old group, n=7) were studied using parallel-imaging-based DTI on a clinical 3T scanner. Compared to young adults, the old monkeys showed 26% lower fractional anisotropy (P<0.01), and 44% greater radial diffusivity, although the latter difference was of marginal statistical significance (P=0.058). These MRI findings are largely consistent with published results of light and electron microscopic studies of optic nerve aging in macaque monkeys, which indicate a loss of fibers and degenerative changes in myelin sheaths. PMID:24649434

  16. Impairment in abstraction and set shifting in aged rhesus monkeys.

    PubMed

    Moore, Tara L; Killiany, Ronald J; Herndon, James G; Rosene, Douglas L; Moss, Mark B

    2003-01-01

    Understanding the nature of changes in cognition with aging has increased in importance as the number of individuals over the age of 65 years grows. To date, studies have demonstrated that age-related changes occur most extensively in the cognitive domains of memory and executive function. Whereas a large number of studies have been conducted about the effects of aging on memory, far less have explored the effects of aging on the so called "executive function" which include abilities essential for successful performance of higher level activities of daily living. As part of our ongoing effort to better characterize these changes, we assessed executive function in a non-human primate model of normal human aging using the Conceptual Set Shifting Task (CSST). This recently developed task assesses abstraction, concept formation and set shifting in the monkey in a way analogous to the Wisconsin Card Sorting Test (WCST) in humans. Relative to young adult monkeys, aged monkeys evidenced significant difficulty in both acquisition and performance on this task, and moreover, demonstrated a high degree of perseverative responding. The pattern of performance displayed by the aged monkeys suggests an age-related decline in prefrontal cortex (PFC) functioning.

  17. Differential expression of anti-glycan antibodies in schistosome-infected humans, rhesus monkeys and mice

    PubMed Central

    Luyai, Anthony E; Heimburg-Molinaro, Jamie; Prasanphanich, Nina Salinger; Mickum, Megan L; Lasanajak, Yi; Song, Xuezheng; Nyame, A Kwame; Wilkins, Patricia; Rivera-Marrero, Carlos A; Smith, David F; Van Die, Irma; Secor, W Evan; Cummings, Richard D

    2014-01-01

    Schistosomiasis is a debilitating parasitic disease of humans, endemic in tropical areas, for which no vaccine is available. Evidence points to glycan antigens as being important in immune responses to infection. Here we describe our studies on the comparative humoral immune responses to defined schistosome-type glycan epitopes in Schistosoma mansoni-infected humans, rhesus monkeys and mice. Rhesus anti-glycan responses over the course of infection were screened on a defined glycan microarray comprising semi-synthetic glycopeptides terminating with schistosome-associated or control mammalian-type glycan epitopes, as well as a defined glycan microarray of mammalian-type glycans representing over 400 glycan structures. Infected rhesus monkeys generated a high immunoglobulin G (IgG) antibody response to the core xylose/core α3 fucose epitope of N-glycans, which peaked at 8–11 weeks post infection, coinciding with maximal ability to kill schistosomula in vitro. By contrast, infected humans generated low antibody levels to this epitope. At 18 months following praziquantel therapy to eliminate the parasite, antibody levels were negligible. Mice chronically infected with S. mansoni generated high levels of anti-fucosylated LacdiNAc (GalNAcβ1, 4(Fucα1, 3)GlcNAc) IgM antibodies, but lacked a robust response to the core xylose/core α3 fucose N-glycan antigens compared with other species studied, and their sera demonstrated an intermediate level of schistosomula killing in vitro. These differential responses to parasite glycan antigens may be related to the ability of rhesus monkeys to self-cure in contrast to the chronic infection seen in humans and mice. Our results validate defined glycan microarrays as a useful technology to evaluate diagnostic and vaccine antigens for schistosomiasis and perhaps other infections. PMID:24727442

  18. Rhesus monkeys (Macaca mulatta) discriminate between knowing and not knowing and collect information as needed before acting.

    PubMed

    Hampton, Robert R; Zivin, Aaron; Murray, Elisabeth A

    2004-10-01

    Humans use memory awareness to determine whether relevant knowledge is available before acting, as when we determine whether we know a phone number before dialing. Such metacognition, or thinking about thinking, can improve selection of appropriate behavior. We investigated whether rhesus monkeys ( Macaca mulatta) are capable of a simple form of metacognitive access to the contents of short-term memory. Monkeys chose among four opaque tubes, one of which concealed food. The tube containing the reward varied randomly from trial to trial. On half the trials the monkeys observed the experimenter baiting the tube, whereas on the remaining trials their view of the baiting was blocked. On each trial, monkeys were allowed a single chance to select the tube containing the reward. During the choice period the monkeys had the opportunity to look down the length of each tube, to determine if it contained food. When they knew the location of the reward, most monkeys chose without looking. In contrast, when ignorant, monkeys often made the effort required to look, thereby learning the location of the reward before choosing. Looking improved accuracy on trials on which monkeys had not observed the baiting. The difference in looking behavior between trials on which the monkeys knew, and trials on which they were ignorant, suggests that rhesus monkeys discriminate between knowing and not knowing. This result extends similar observations made of children and apes to a species of Old World monkey, suggesting that the underlying cognitive capacities may be widely distributed among primates.

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

    PubMed Central

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

    2016-01-01

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

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

    PubMed Central

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

    2011-01-01

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

  1. Profiling serum antibodies to Mycobacterium tuberculosis proteins in rhesus monkeys with nontuberculous Mycobacteria.

    PubMed

    Min, Fangui; Pan, Jinchun; Wu, Ruike; Chen, Meiling; Kuang, Huiwen; Zhao, Weibo

    2016-01-01

    Recent evidence indicates that the prevalence of diseases caused by nontuberculous mycobacteria (NTM) has been increasing in both human and animals. In this study, antibody profiles of NTM in rhesus monkeys (Macaca mulatta) were determined and compared with those of monkeys infected with Mycobacterium tuberculosis complex (MTBC). Antibodies against 10 M. tuberculosis proteins, purified protein derivative (PPD), and mammalian old tuberculin (MOT) were detected in 14 monkeys naturally infected with NTM by indirect ELISA. Sera from 10 monkeys infected with MTBC and 10 healthy monkeys were set as controls. All antigens showed high serological reactivities to MTBC infections and low reactivities in healthy monkeys. NTM infections showed strong antibody responses to MOT and PPD; moderate antibody responses to 16kDa, U1, MPT64L, 14kDa, and TB16.3; and low antibody responses to 38kDa, Ag85b, CFP10, ESAT-6, and CFP10-ESAT-6. According to the criteria of MTBC, only CFP10, ESAT-6, and CFP10-ESAT-6 showed negative antibody responses in all NTM infections. Taken together, these results suggest that positive results of a PPD/MOT-based ELISA in combination with results of antibodies to M. tuberculosis-specific antigens, such as CFP10 and ESAT-6, could discriminate NTM and MTBC infections. Two positive results indicate an MTBC infection, and a negative result for an M. tuberculosis-specific antigen may preliminarily predict an NTM infection.

  2. Profiling serum antibodies to Mycobacterium tuberculosis proteins in rhesus monkeys with nontuberculous Mycobacteria

    PubMed Central

    Min, Fangui; Pan, Jinchun; Wu, Ruike; Chen, Meiling; Kuang, Huiwen; Zhao, Weibo

    2015-01-01

    Recent evidence indicates that the prevalence of diseases caused by nontuberculous mycobacteria (NTM) has been increasing in both human and animals. In this study, antibody profiles of NTM in rhesus monkeys (Macaca mulatta) were determined and compared with those of monkeys infected with Mycobacterium tuberculosis complex (MTBC). Antibodies against 10 M. tuberculosis proteins, purified protein derivative (PPD), and mammalian old tuberculin (MOT) were detected in 14 monkeys naturally infected with NTM by indirect ELISA. Sera from 10 monkeys infected with MTBC and 10 healthy monkeys were set as controls. All antigens showed high serological reactivities to MTBC infections and low reactivities in healthy monkeys. NTM infections showed strong antibody responses to MOT and PPD; moderate antibody responses to 16kDa, U1, MPT64L, 14kDa, and TB16.3; and low antibody responses to 38kDa, Ag85b, CFP10, ESAT-6, and CFP10-ESAT-6. According to the criteria of MTBC, only CFP10, ESAT-6, and CFP10-ESAT-6 showed negative antibody responses in all NTM infections. Taken together, these results suggest that positive results of a PPD/MOT-based ELISA in combination with results of antibodies to M. tuberculosis-specific antigens, such as CFP10 and ESAT-6, could discriminate NTM and MTBC infections. Two positive results indicate an MTBC infection, and a negative result for an M. tuberculosis-specific antigen may preliminarily predict an NTM infection. PMID:26437786

  3. 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.

  4. 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…

  5. Pathology of Lassa Virus Infection in the Rhesus Monkey

    DTIC Science & Technology

    1982-01-01

    examined. Lassa fever ’- is an infectious, febrile disease nuclear cell infiltrates and mucosal hemorrhages. of man caused by Lassa virus (LASV), a member... virus titers, suggests that virus replication 1. Buckley, S. M., and Casals, J., 1973. Lassa fever , in the kidney parenchyma was unlikely. A few a new...A., 1973. Comparative pathology of phology and morphogenesis of arenaviruses . BDg. Lassa virus infection in monkeys, guinea pip, W.H.O., 52: 409-419

  6. Long Term Mortality and Cancer Risk in Irradiated Rhesus Monkeys

    DTIC Science & Technology

    1990-05-01

    energy to oenetrate the total body thickness require higher surface doses to induce lethality during the acute radiation sickness phase (within 100...Whether it is spontaneous or radiation - induced , untreated endometriosis in monkeys is often life-threatening due to the size and invasiveness of the...disregarded in the determination of probability of death due to cancer. If the same genetic factors that predispose individuals to radiation - induced cancer

  7. 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.

  8. 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

  9. Long-Term Effects of Castration on the Skeleton of Male Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    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.

    2015-01-01

    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. PMID:25771746

  10. Long-term vasectomy: effects on the occurrence and extent of atherosclerosis in rhesus monkeys.

    PubMed Central

    Clarkson, T B; Alexander, N J

    1980-01-01

    We demonstrated previously that atherosclerosis develops more extensively in vasectomized cynomolgus macaques fed an atherogenic diet and speculated that the immunologic response to sperm antigens may have exacerbated the atherosclerosis. We report here that rhesus monkeys vasectomized for 9-14 yr and fed monkey chow (devoid of cholesterol and low in fat) rather than an atherogenic diet also had more extensive and severe atherosclerosis than did control animals of the same age. The extent of atherosclerosis was considered as the percentage of intimal surface with plaques. No control animals were found to have plaques in the thoracic aorta, but 7 of 10 vasectomized monkeys were affected. The plaques in the vasectomized monkeys occupied about 13% of the intimal surface. In 4 of 7 control monkeys and 7 of 10 vasectomized monkeys there were lesions in the abdominal aortas; the lesions were considerably more extensive and severe in the vasectomized animals. Lesions were also more common in iliac arteries of vasectomized animals, and the extent was increased about threefold. Plaques were seen at the carotid bifurcation in all of the animals of both the control and vasectomized groups. The carotid bifurcation plaques of the vasectomized monkeys were larger than those of the control animals on the right but not on the left side. Histologically, the lesions of vasectomized monkeys did not appear to be qualitatively different from those of control animals, even though they were larger and contained more collagen, lipid, and mucopolysaccharides. Grossly, the distribution of the lesions in the vasectomized animals was different from that in the control animals, and that of lesions induced by atherogenic diets, i.e., the lesions were distributed randomly within the artery rather than around bifurcations. More extensive atherosclerosis was noted among vasectomized animals that were found to lack demonstrable circulating free antisperm antibodies. On the basis of the observations

  11. 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.

  12. Edinger-Westphal and pharmacologically stimulated accommodative refractive changes and lens and ciliary process movements in rhesus monkeys.

    PubMed

    Ostrin, Lisa A; Glasser, Adrian

    2007-02-01

    During accommodation, the refractive changes occur when the ciliary muscle contracts, releasing resting zonular tension and allowing the lens capsule to mold the lens into an accommodated form. This results in centripetal movement of the ciliary processes and lens edge. The goal of this study was to understand the relationship between accommodative refractive changes, ciliary process movements and lens edge movements during Edinger-Westphal (EW) and pharmacologically stimulated accommodation in adolescent rhesus monkeys. Experiments were performed on one eye each of three rhesus monkeys with permanent indwelling electrodes in the EW nucleus of the midbrain. EW stimulated accommodative refractive changes were measured with infrared photorefraction, and ciliary process and lens edge movements were measured with slit-lamp goniovideography on the temporal aspect of the eye. Images were recorded on the nasal aspect for one eye during EW stimulation. Image analysis was performed off-line at 30 Hz to determine refractive changes and ciliary body and lens edge movements during EW stimulated accommodation and after carbachol iontophoresis to determine drug induced accommodative movements. Maximum EW stimulated accommodation was 7.36+/-0.49 D and pharmacologically stimulated accommodation was 14.44+/-1.21 D. During EW stimulated accommodation, the ciliary processes and lens edge moved centripetally linearly by 0.030+/-0.001 mm/D and 0.027+/-0.001 mm/D, with a total movement of 0.219+/-0.034 mm and 0.189+/-0.023 mm, respectively. There was no significant nasal/temporal difference in ciliary process or lens edge movements. 30-40 min after pharmacologically stimulated accommodation, the ciliary processes moved centripetally a total of 0.411+/-0.048 mm, or 0.030+/-0.005 mm/D, and the lens edge moved centripetally 0.258+/-0.014 mm, or 0.019+/-0.003 mm/D. The peaks and valleys of the ciliary processes moved by similar amounts during both supramaximal EW and pharmacologically

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  14. 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

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

    PubMed Central

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

    2010-01-01

    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 would treat empty sets as numerical values. All monkeys successfully matched and ordered the empty sets without any training. Accuracy showed distance effects, indicating that they treated empty sets as values on a numerical continuum. PMID:19397383

  16. 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

  17. 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.

  18. Plasmodium coatneyi in the rhesus monkey (Macaca mulatta) as a model of malaria in pregnancy.

    PubMed

    Davison, B B; Cogswell, F B; Baskin, G B; Falkenstein, K P; Henson, E W; Tarantal, A F; Krogstad, D J

    1998-08-01

    Pregnant women with Plasmodium falciparum infection are at increased risk for complications such as anemia and cerebral malaria. In addition, the infants of these women suffer intrauterine growth retardation (IUGR), low birth weight (LBW), congenital infection, and high infant mortality. Although much has been learned from studies of malaria during human pregnancy, progress has been limited by the lack of a suitable animal model. Nonhuman primates are of particular interest because, other than the armadillo, they are the only animals with a discoidal, villous, hemochorial placenta like that of humans. We have established a model of malaria during human pregnancy by inoculating pregnant rhesus monkeys (Macaca mulatta) with Plasmodium coatneyi (a sequestering parasite) during the first trimester. In our initial experiment, four monkeys were inoculated with a fresh inoculum containing 10(8) viable parasites from an infected donor monkey. All four monkeys became parasitemic seven days postinoculation (PI) and three monkeys aborted 7-10 days PI coincident with high peak parasitemias (41,088-374,325 parasites/mm3). Although abortion is one of the outcomes observed in Plasmodium-infected women, the intent of this study was to examine the effects of Plasmodium infection throughout gestation. Since the rapid onset of high parasitemia may have been responsible for the abortions, a decision was made to reduce the size of the effective inoculum. Six additional pregnant monkeys were inoculated with a frozen isolate taken from the same donor containing 10(6) parasites. These six animals became parasitemic by 14 days PI and, along with monkey E412, carried their infants to term. These seven infants weighed significantly less at term than the infants of uninfected mothers (P = 0.0355). Symmetrical IUGR was detected by ultrasound in one fetus with an LBW of 334 g. Another LBW infant (300 g) had asymmetrical growth retardation, which has been associated with uteroplacental

  19. Iron deficiency anemia and affective response in rhesus monkey infants.

    PubMed

    Golub, Mari S; Hogrefe, Casey E; Widaman, Keith F; Capitanio, John P

    2009-01-01

    Infant iron deficiency anemia (IDA) occurs spontaneously in monkey populations as it does in humans, providing a model for understanding effects on brain and behavior. A set of 34 monkey infants identified as IDA (hemoglobin <11 g/dl) over a 5-year period at the California National Primate Research Center (CNPRC) was compared to a set of 57 controls (hemoglobin >12 g/dl) matched for age and caging location. The infants had participated in a Biobehavioral Assessment conducted at 3-4 months of age at CNPRC that included measures of behavioral and adrenocortical response to a novel environment. IDA males differed from control males in two factors ("activity," "emotionality") derived from observational data taken on the first and second day of the exposure to the novel environment. In the male infants, IDA was associated with less restriction of activity in the novel environment on both days and less emotionality on the second day (p < .05). IDA males also displayed less response to approach by a human (human intruder test) than did control males. IDA females did not differ from controls. Adrenocortical response was not significantly affected. These findings may be relevant to functional deficits in human infants with IDA that influence later behavior.

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

    PubMed Central

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

    2010-01-01

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

  1. 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

  2. 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

  3. Mirror-induced self-directed behaviors in rhesus monkeys after visual-somatosensory training.

    PubMed

    Chang, Liangtang; Fang, Qin; Zhang, Shikun; Poo, Mu-ming; Gong, Neng

    2015-01-19

    Mirror self-recognition is a hallmark of higher intelligence in humans. Most children recognize themselves in the mirror by 2 years of age. In contrast to human and some great apes, monkeys have consistently failed the standard mark test for mirror self-recognition in all previous studies. Here, we show that rhesus monkeys could acquire mirror-induced self-directed behaviors resembling mirror self-recognition following training with visual-somatosensory association. Monkeys were trained on a monkey chair in front of a mirror to touch a light spot on their faces produced by a laser light that elicited an irritant sensation. After 2-5 weeks of training, monkeys had learned to touch a face area marked by a non-irritant light spot or odorless dye in front of a mirror and by a virtual face mark on the mirroring video image on a video screen. Furthermore, in the home cage, five out of seven trained monkeys showed typical mirror-induced self-directed behaviors, such as touching the mark on the face or ear and then looking at and/or smelling their fingers, as well as spontaneously using the mirror to explore normally unseen body parts. Four control monkeys of a similar age that went through mirror habituation but had no training of visual-somatosensory association did not pass any mark tests and did not exhibit mirror-induced self-directed behaviors. These results shed light on the origin of mirror self-recognition and suggest a new approach to studying its neural mechanism.

  4. Prophylactic Ribavirin Treatment of Dengue Type 1 Infection in Rhesus Monkeys

    DTIC Science & Technology

    1990-01-01

    Fever ,nd Dengue , 15-19 May 1988, Rio de Janeiro. Brazil . Pifat. D.Y., Toribio, F.E., Watson. K.A. and Canonico, P.G. (1990) Effect of human recombinant...FITr’ c COPy 2 Antiviral Research, 13 (1990) 139-150 q Elsevier AVR 00405 Prophylactic ribavirin treatment of dengue type 1 infection in rhesus...with dengue virus. Both placebo- and ribavirin-treated monkeys developed viremia, as measured by direct plaque assay on Aedes albopictus C6/36 cells

  5. Characterization of Soman Toxicity in Atropine and Oxime (HI-6 and MMB- 4) Treated Rhesus Monkeys

    DTIC Science & Technology

    1991-03-30

    Challenged Rhesus Monkeys Pretreated with Pyridostigmine Bromi deo. 3 15. Approval Signatures: P Carl T. 0lson, 0.V.M., Ph.D. t- .3 Study Director P...taken to avoid open flame or heat that may ignite them. F. Safety Regulrements: S 1. Hoods: Hood face velocity must average 100 L 10 Ifpm. The average...S thickness Carrier Gas: Helium Velocity : 30 L S ca/sec for Helium Hake-up Gas: 30 L S *lamin Detector : Flame Ionization Detector (FIO) Oetector

  6. Effects of Head-down Tilt on Nerve Conduction in Rhesus Monkeys

    PubMed Central

    Sun, Bo; Zhang, Xiao-Yun; Liu, Li-Zhi; Chen, Zhao-Hui; Dai, Zhong-Quan; Huang, Xu-Sheng

    2017-01-01

    Background: Few studies have focused on peripheral nerve conduction during exposure to microgravity. The −6° head-down tilt (HDT) comprises an experimental model used to simulate the space flight environment. This study investigated nerve conduction characteristics of rhesus monkeys before and after prolonged exposure to HDT. Methods: Six rhesus monkeys (3–4 years old) were tilted backward 6° from the horizontal. Nerve conduction studies (NCSs) were performed on the median, ulnar, tibial, and fibular motor nerves. Analysis of variance with a randomized block design was conducted to compare the differences in the NCS before and 7, 21, and 42 days after the −6° HDT. Results: The proximal amplitude of the CMAP of the median nerve was significantly decreased at 21 and 42 days of HDT compared with the amplitude before HDT (4.38 ± 2.83 vs. 8.40 ± 2.66 mV, F = 4.85, P = 0.013 and 3.30 ± 2.70 vs. 8.40 ± 2.66 mV, F = 5.93, P = 0.004, respectively). The distal amplitude of the CMAP of the median nerve was significantly decreased at 7, 21, and 42 days of HDT compared with the amplitude before HDT (7.28 ± 1.27 vs. 10.25 ± 3.40 mV, F = 4.03, P = 0.039; 5.05 ± 2.01 vs. 10.25 ± 3.40 mV, F = 6.25, P = 0.04; and 3.95 ± 2.79 vs. 10.25 ± 3.40 mV, F = 7.35, P = 0.01; respectively). The proximal amplitude of the CMAP of the tibial nerve was significantly decreased at 42 days of HDT compared with the amplitude before HDT (6.14 ± 1.94 vs. 11.87 ± 3.19 mV, F = 5.02, P = 0.039). Conclusions: This study demonstrates that the compound muscle action potential amplitudes of nerves are decreased under simulated microgravity in rhesus monkeys. Moreover, rhesus monkeys exposed to HDT might be served as an experimental model for the study of NCS under microgravity. PMID:28139516

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

    PubMed Central

    KESSLER, MATTHEW J.; RAWLINS, RICHARD G.

    2015-01-01

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

  8. 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.

  9. Aberrant genomic imprinting in rhesus monkey embryonic stem cells.

    PubMed

    Fujimoto, Akihisa; Mitalipov, Shoukhrat M; Kuo, Hung-Chih; Wolf, Don P

    2006-03-01

    Genomic imprinting involves modification of a gene or a chromosomal region that results in the differential expression of parental alleles. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. Additionally, abnormal imprinting occurs in mouse embryonic stem cells (ESCs) and in clonally derived animals. Imprinted gene expression patterns in primate ESCs are largely unknown, despite the clinical potential of the latter in the cell-based treatment of human disease. Because of the possible implications of abnormal gene expression to cell or tissue replacement therapies involving ESCs, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ESC lines containing useful single nucleotide polymorphisms were subjected to polymerase chain reaction-based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting whereas IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ESCs, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ESC progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ESC differentiation in vitro and on ESC-derived cell function in vivo after transplantation are unknown.

  10. Determination of the Infectious Dose of Helicobacter pylori during Primary and Secondary Infection in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Solnick, Jay V.; Hansen, Lori M.; Canfield, Don R.; Parsonnet, Julie

    2001-01-01

    We sought to determine the infectious dose of Helicobacter pylori during primary and secondary infection in the rhesus monkey and to determine whether preinoculation acid suppression is necessary to produce colonization. Mixed inoculation with three human-derived strains showed that H. pylori J166 is particularly adapted to colonization of rhesus monkeys, since it outcompeted two other strains. The minimum infectious dose of H. pylori J166 was 104 bacteria in specific-pathogen (H. pylori)-free monkeys. Rechallenge of these monkeys after antibiotic therapy was characterized by a 10- to 100-fold decrease in bacterial load compared to primary infection, but with little change in the infectious dose. Acid suppression prior to inoculation was not necessary for colonization to occur. These results provide a basis for future animal experiments using more ecologically relevant conditions of inoculation and suggest that reduction in bacterial load rather than complete protection may be a more realistic goal for H. pylori vaccination. PMID:11598063

  11. Checking behavior in rhesus monkeys is related to anxiety and frontal activity

    PubMed Central

    Bosc, Marion; Bioulac, Bernard; Langbour, Nicolas; Nguyen, Tho Hai; Goillandeau, Michel; Dehay, Benjamin; Burbaud, Pierre; Michelet, Thomas

    2017-01-01

    When facing doubt, humans can go back over a performed action in order to optimize subsequent performance. The present study aimed to establish and characterize physiological doubt and checking behavior in non-human primates (NHP). We trained two rhesus monkeys (Macaca mulatta) in a newly designed “Check-or-Go” task that allows the animal to repeatedly check and change the availability of a reward before making the final decision towards obtaining that reward. By manipulating the ambiguity of a visual cue in which the reward status is embedded, we successfully modulated animal certainty and created doubt that led the animals to check. This voluntary checking behavior was further characterized by making EEG recordings and measuring correlated changes in salivary cortisol. Our data show that monkeys have the metacognitive ability to express voluntary checking behavior similar to that observed in humans, which depends on uncertainty monitoring, relates to anxiety and involves brain frontal areas. PMID:28349919

  12. Radiographic Incidence of Spinal Osteopathologies in Captive Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Hernández-Godínez, Braulio; Ibáñez-Contreras, Alejandra; Perdigón-Castañeda, Gerardo; Galván-Montaño, Alfonso; de Oca, Guadalupe García-Montes; Zapata-Valdez, Carinthia; Tena-Betancourt, Eduardo

    2010-01-01

    Degenerative spinal disease is a leading cause of chronic disability both in humans and animals. Although widely seen as a normal occurrence of aging, degenerative spinal disease can be caused by various genetic, iatrogenic, inflammatory, and congenital factors. The objective of this study was to characterize the degenerative spine-related diseases and the age at onset in a random subpopulation of 20 captive rhesus monkeys (Macaca mulatta; male, 13; female, 7; age: range, 4 to 27 y; median, 18.5 y). Spinal radiographic evaluation (left lateral, right lateral, and ventrodorsal views) of the spinal column (C1 to S1) was performed, and spinal degenerative disease was scored. The incidence of osteopathology was higher in the 14- to 18-y-old group, but incidence did not differ according to sex. In the studied population, degenerative changes were present in monkeys as young as 9 y of age. PMID:21262126

  13. Preclinical evaluation of a urokinase plasminogen activator receptor-targeted nanoprobe in rhesus monkeys

    PubMed Central

    Chen, Yushu; Gong, Li; Gao, Ning; Liao, Jichun; Sun, Jiayu; Wang, Yuqing; Wang, Lei; Zhu, Pengjin; Fan, Qing; Wang, Yongqiang Andrew; Zeng, Wen; Mao, Hui; Yang, Lily; Gao, Fabao

    2015-01-01

    Purpose To translate a recombinant peptide containing the amino-terminal fragment (ATF) of urokinase plasminogen activator receptor-targeted magnetic iron oxide (IO) nanoparticles (uPAR-targeted human ATF-IONPs) into clinical applications, we conducted a pilot study to evaluate the toxicity and pharmacokinetics of this nanoparticle in normal rhesus monkeys. Methods We assessed the changes in the following: magnetic resonance imaging (MRI) signals from pretreatment stage to 14 days posttreatment, serum iron concentrations from 5 minutes posttreatment to 12 weeks posttreatment, routine blood examination and serum chemistry analysis results from pretreatment stage to 12 weeks after administration, and results of staining of the liver with Perls’ Prussian Blue and hematoxylin–eosin at 24 hours and 3 months posttreatment in two rhesus monkeys following an intravenous administration of the targeted nanoparticles either with a polyethylene glycol (ATF-PEG-IONP) or without a PEG (ATF-IONP) coating. Results The levels of alkaline phosphatase, alanine transaminase, and direct bilirubin in the two monkeys increased immediately after the administration of the IONPs but returned to normal within 20 days and stayed within the normal reference range 3 months after the injection. The creatinine levels of the two monkeys stayed within the normal range during the study. In addition, red blood cells, white blood cells, hemoglobin level, and platelets remained normal during the 3 months of the study. Conclusion All of the results suggest that a transient injury in terms of normal organ functions, but no microscopic necrotic lesions, was observed at a systemic delivery dose of 5 mg/kg of iron equivalent concentration in the acute phase, and that no chronic toxicity was found 3 months after the injection. Therefore, we conclude that uPAR-targeted IONPs have the potential to be used as receptor-targeted MRI contrasts as well as theranostic agents for the detection and treatment of

  14. Diet-induced iron deficiency anemia and pregnancy outcome in rhesus monkeys12

    PubMed Central

    Golub, Mari S; Hogrefe, Casey E; Tarantal, Alice F; Germann, Stacey L; Beard, John L; Georgieff, Michael K; Calatroni, Agustin; Lozoff, Betsy

    2006-01-01

    Background Iron deficiency anemia (IDA) is relatively common in the third trimester of pregnancy, but causal associations with low birth weight and compromised neonatal iron status are difficult to establish in human populations. Objective The objective was to determine the effects of diet-induced IDA on intrauterine growth and neonatal iron status in an appropriate animal model for third-trimester IDA in women. Design Hematologic and iron-status measures, pregnancy outcomes, and fetal and neonatal evaluations were compared between pregnant rhesus monkeys (n = 14) fed a diet containing 10 μg Fe/g diet from the time of pregnancy detection (gestation days 28–30) and controls (n = 24) fed 100 μg Fe/g diet. Results By the third trimester, 79% of the iron-deprived dams and 29% of the control monkeys had a hemoglobin concentration <11 g/dL. There were also significant group differences in hematocrit, mean corpuscular volume, transferrin saturation, serum ferritin, and serum iron. At birth, the newborns of monkeys iron-deprived during pregnancy had significantly lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin values and a lower ratio of erythroid to total colony-forming units in bone marrow than did the control newborns. Pregnancy weight gain did not differ significantly between the iron-deprived and control dams, and the fetuses and newborns of the iron-deprived dams were not growth retarded relative to the controls. Gestation length, the number of stillbirths, and neonatal neurobehavioral test scores did not differ significantly by diet group. Conclusion These data indicate that an inadequate intake of iron from the diet during pregnancy in rhesus monkeys can lead to compromised hematologic status of the neonate without indications of growth retardation or impaired neurologic function at birth. PMID:16522913

  15. 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.

  16. 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.

  17. [Pharmacokinetics of salvianolic acid A after single intravenous administration in Rhesus monkey].

    PubMed

    Song, Jun-ke; Zhang, Wen; Zhang, Wei-ku; Feng, Zhang-ying; Xie, Tao; Du, Guan-Hua

    2015-09-01

    Salvianolic acid A (Sal A) is one of the most effective compounds isolated from the root of Salvia miltiorrhiza. Up to now, several studies regarding the pharmacokinetic profiles of Sal A have been reported, however there is no such study reported in monkeys, the species which is more similar to human. The aim of this study is to develop a LC-MS method for the determination of Sal A in monkey plasma and apply it to the pharmacokinetic studies of monkeys. After single intravenous administration of Sal A, the plasma concentration-time curves were observed and the main pharmacokinetic parameters were calculated. The plasma concentration at 2 min (C2 (min)) values were (28.343 ± 6.426), (45.679 ± 12.301) and (113.293 ± 24.360) mg x L(-1) for Rhesus monkeys treated with Sal A at 2.5, 5 and 10 mg x kg(-1). The area under the concentration-time curve (AUC(0-∞)) values were (3.316 ± 0.871), (5.754 ± 2.150) and (13.761 ± 2.825) μg x L(-1) x h, respectively. Furthermore, this method was improved and applied to the simultaneous determination of Sal A, Sal B and Sal C, which provided useful information for preclinical studies and clinical trials of Sal A, Sal B and Sal C.

  18. Interactions between delta9-tetrahydrocannabinol and heroin: self-administration in rhesus monkeys

    PubMed Central

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

    2014-01-01

    The cannabinoid receptor agonist delta9-tetrahydrocannabinol (THC) enhances the antinociceptive effects of mu 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 i.v. 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 to 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 the individual drugs. PMID:23044830

  19. Assessment of motor function of the hand in aged rhesus monkeys.

    PubMed

    Moore, Tara L; Killiany, Ronald J; Pessina, Monica A; Moss, Mark B; Rosene, Douglas L

    2010-01-01

    In the elderly, intact motor functions of the upper extremity are critical for the completion of activities of daily living. Many studies have provided insight into age-related changes in motor function. However, the precise nature and extent of motor impairments of the upper extremity remains unclear. In the current study we have modified two tasks to assess hand/digit function in both young and aged rhesus monkeys. We tested monkeys from 9 to 26 years of age on these tasks to determine the level of fine motor performance across the adult age range. Compared to young monkeys (9-12 years of age), aged monkeys (15-26 years of age) were mildly impaired on fine motor control of the digits. These findings are consistent with previous studies that have found age-related impairment in fine motor function. However, the magnitude and extent of impairment in the current study does differ from previous findings and is likely due to methodological differences in the degree of task complexity.

  20. STUDIES ON ACUTE DISSEMINATED ENCEPHALOMYELITIS PRODUCED EXPERIMENTALLY IN RHESUS MONKEYS

    PubMed Central

    Lumsden, Charles E.; Kabat, Elvin A.; Wolf, Abner; Bezer, Ada E.

    1950-01-01

    1. Animals injected with emulsions of monkey brain with adjuvants show a complex pattern of antibody response as determined by complement fixation tests. 2. Organ-specific complement-fixing antibodies to constituents of brain tissue may be formed which fix complement with brain tissues of various animal species but fail to react with other organs or with rabbit placenta. 3. Antibodies may be formed to some constituent of brain other than nervous tissue. It would seem that these can be detected by the strong complement fixation given with rabbit placenta. 4. Sera from individual animals may contain antibodies to the brain or placenta constituents, to both, or to neither. Occasional individual sera show unique patterns of antibody response as determined with various additional antigens such as fetal brain, posterior pituitary, or peripheral nerves. 5. No evidence of any etiological relationship between the development of encephalomyelitis and the complement-fixing antibodies to brain demonstrable in the sera could be found. The complement-fixing antibody to the placental constituent was unrelated to the encephalomyelitis. PMID:15436935

  1. 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.

  2. Metabolizable energy intake during long-term calorie restriction in rhesus monkeys.

    PubMed

    Raman, Aarthi; Baum, Scott T; Colman, Ricki J; Kemnitz, Joseph W; Weindruch, Richard; Schoeller, Dale A

    2007-10-01

    Calorie restriction (CR) is a dietary intervention shown to increase maximum life-span. The aim of this study was to compare the metabolizable energy of the pelleted semi-purified diet with estimated energy intake from food weight. Energy density of diet, urine and feces were measured by bomb calorimetry in rhesus monkeys (23-29 years old) on CR (CR, n=11) and control (C, n=9). Food moisture was measured to be 2-fold higher (9+/-1%) than indicated on the label (approximately 5%). The measured gross energy of diet was 4.4 kcal/g dry weight of CR and 4.5 kcal/g dry weight of C diets. In a two-day trial, food intake (mean+/-SD) was 112+/-20 g and 136+/-26 g of dry mass/d in the CR and C monkeys, respectively (p=0.003). The fraction of the diet absorbed (CR=0.91; C=0.95) was different (p<0.001) between CR and C monkeys. Using these coefficients, the metabolizable energy intake averaged over 6 months was 450+/-53 and 534+/-97 kcal/d in CR and C monkeys, respectively (Diff=16%; p=0.03). These values were compared with energy expenditure (EE), as measured annually by indirect calorimetry (490+/-61 kcal/d in CR and 532+/-62 kcal/d in C monkeys). Adjusted for changes in body composition (2+/-10 kcal/d in CR and -7+/-12 kcal/d in C), energy balance was not different from zero in CR (-42+/-42 kcal/d) and C (9+/-61 kcal/d) monkeys. Use of diet weight is a reasonable estimate of the level of CR when food waste is assessed.

  3. Effectiveness of spiramycin for treatment of congenital Toxoplasma gondii infection in rhesus monkeys.

    PubMed Central

    Schoondermark-Van de Ven, E; Melchers, W; Camps, W; Eskes, T; Meuwissen, J; Galama, J

    1994-01-01

    The effectiveness of spiramycin for the treatment of rhesus monkey fetuses congenitally infected with Toxoplasma gondii was studied. Eight monkeys were infected at day 90 of pregnancy. This is comparable to the second trimester of organogenetic development in humans. Transmission of infection was found prenatally in five of the eight monkeys by detection of the parasite in the amniotic fluid. Treatment with spiramycin (20 mg/kg/day in two intermittent doses given intravenously) was started as soon as fetal infection was proven and was continued until birth. Nine to 14 days after initiation of treatment, the parasite was still detectable in amniotic fluid samples from four of these five cases. However, the parasite was detected only by PCR and not by mouse inoculation. T. gondii was also detected only by PCR in the placenta of one monkey that delivered prematurely. This monkey received spiramycin treatment for only 2 weeks. In the four monkeys that received treatment for about 7 weeks, the parasite was not present at birth in the placenta nor in amniotic fluid or neonatal organs. Spiramycin accumulates mainly in maternal tissues. Although concentrations in neonatal tissue were found to be 5 to 28 times higher than the corresponding concentrations in neonatal serum, the concentrations in neonatal tissue were still 11 to 16 times lower than those found in the mothers. However, no spiramycin was found in the fetal brains. Early treatment with spiramycin may prevent transmission of infection to the fetus but most probably cannot interrupt an existing brain infection, which is the most severe outcome of congenital toxoplasmosis in humans. Images PMID:7811000

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

    PubMed

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

    2016-06-02

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

  5. 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…

  6. 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.

  7. 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

  8. Mass spectral characterization of doxylamine and its rhesus monkey urinary metabolites.

    PubMed

    Holder, C L; Korfmacher, W A; Slikker, W; Thompson, H C; Gosnell, A B

    1985-04-01

    This study describes the use of mass spectrometry (MS), high-performance liquid chromatography (HPLC) and chemical derivatization techniques for the identification of doxylamine and five rhesus monkey urinary metabolites. The analyses were performed using chemical ionization mass spectrometry with either methane or ammonia as the reagent gas. The confirmation of the structures of two of these urinary metabolites was aided by the synthesis of doxylamine N-oxide and desmethyldoxylamine and by the use of methylation and acetylation derivatization techniques. Doxylamine N-oxide, desmethyldoxylamine, didesmethyldoxylamine, and two metabolites which resulted from the cleavage of the aliphatic tertiary nitrogen side chain to the subsequent 2-[1-phenyl-1-(2-pyridinyl)ethoxy]acetic acid or 2-[1-phenyl-1-(2-pyridinyl)ethoxy]methanol compounds were isolated and identified from rhesus monkey urine. Additional data concerning the mass spectral analysis of derivatization or reaction products from the three chloroformate reactions with doxylamine, and the synthesis and separation techniques which afforded mass spectral identification of the urinary metabolites are also presented.

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

    PubMed

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

    1989-01-01

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

  10. Ultrastructural evidence for impaired mitochondrial fission in the aged rhesus monkey dorsolateral prefrontal cortex.

    PubMed

    Morozov, Yury M; Datta, Dibyadeep; Paspalas, Constantinos D; Arnsten, Amy F T

    2017-03-01

    Dorsolateral prefrontal cortex mediates high-order cognitive functions that are impaired early in the aging process in monkeys and humans. Here, we report pronounced changes in mitochondrial morphology in dendrites of dorsolateral prefrontal cortex neurons from aged rhesus macaques. Electron microscopy paired with 3D reconstruction from serial sections revealed an age-related increase in mitochondria with thin segments that intermingled with enlarged ones, the 'mitochondria-on-a-string' phenotype, similar to those recently reported in patients with Alzheimer's disease. The thin mitochondrial segments were associated with endoplasmic reticulum cisterns, and the mitochondrial proteins Fis1 and Drp1, all of which initiate mitochondrial fission. These data suggest that the 'mitochondria-on-a-string' phenotype may reflect malfunction in mitochondrial dynamics, whereby fission is initiated, but the process is incomplete due to malfunction of subsequent step(s). Thus, aged rhesus monkeys may be particularly helpful in exploring the age-related changes that render higher cortical circuits so vulnerable to degeneration.

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

    PubMed Central

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

    2008-01-01

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

  12. 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…

  13. 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.

  14. 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

  15. Manganese inhalation by rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity.

    PubMed

    Erikson, Keith M; Dorman, David C; Lash, Lawrence H; Aschner, Michael

    2007-06-01

    The purpose of this study was to evaluate biochemical markers of neurotoxicity following subchronic manganese sulfate (MnSO(4)) inhalation. Juvenile rhesus monkeys were exposed to MnSO(4) at 0, 0.06, 0.3, or 1.5 mg Mn/m(3) for 65 days. Glutamine synthetase (GS), glutamate transporters (glutamate transporter-1 [GLT-1] and glutamate/aspartate transporter [GLAST]) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), GLT-1, GLAST, TH and GS mRNA levels, and total glutathione (GSH) levels were assessed in known targets (caudate, globus pallidus, putamen) as well as the cerebellum, frontal cortex, and olfactory cortex. All MnSO(4)-exposed monkeys had decreased pallidal GS protein, decreased caudate GLT-1 mRNA, decreased pallidal GLAST protein, and increased olfactory cortical TH mRNA levels. Monkeys exposed to MnSO(4) at 0.06 or 0.3 mg Mn/m(3) had significantly increased pallidal mRNA levels for GLT-1, GLAST, and TH. Monkeys exposed to MnSO(4) at > or = 0.3 mg Mn/m(3) had several alterations including decreased frontal cortical MT mRNA, decreased caudate, globus pallidus, olfactory cortex, and cerebellum GLT-1 protein, decreased olfactory cortex and cerebellum GLAST protein, increased cerebellar GLAST mRNA, and decreased pallidal TH protein levels. Lastly, GSH levels were significantly increased in the frontal cortex and decreased in the caudate of monkeys exposed to the 1.5-mg Mn/m(3) compared to the controls. Overall, as in our previous studies, we observed that increased Mn concentrations due to airborne Mn exposure differentially affects biomarkers in each brain region (e.g., GSH was increased in the frontal cortex and decreased in the caudate despite two- to threefold increases in Mn concentrations in these regions).

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

    PubMed Central

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

    2017-01-01

    Attentional set-shifting ability is an executive function underling cognitive flexibility in humans and animals. In humans, this function is typically observed during a single experimental session where dimensions of playing cards are used to measure flexibility in the face of changing rules for reinforcement (i.e., the Wisconsin Card Sorting Test (WCST)). In laboratory animals, particularly non-human primates, variants of the WCST involve extensive training and testing on a series of dimensional discriminations, usually in social isolation. In the present study, a novel experimental approach was used to assess attentional set-shifting simultaneously in 12 rhesus monkeys. Specifically, monkeys living in individual cages but in the same room were trained at the same time each day in a set-shifting task in the same housing environment. As opposed to the previous studies, each daily session began with a simple single-dimension discrimination regardless of the animal’s performance on the previous session. A total of eight increasingly difficult, discriminations (sets) were possible in each daily 45 min session. Correct responses were reinforced under a second-order schedule of flavored food pellet delivery, and criteria for completing a set was 12 correct trials out of a running total of 15 trials. Monkeys progressed through the sets at their own pace and abilities. The results demonstrate that all 12 monkeys acquired the simple discrimination (the first set), but individual differences in the ability to progress through all eight sets were apparent. A performance index (PI) that encompassed progression through the sets, errors and session duration was calculated and used to rank each monkey’s performance in relation to each other. Overall, this version of a set-shifting task results in an efficient assessment of reliable differences in cognitive flexibility in a group of monkeys. PMID:28386222

  17. Physical activity of adult female rhesus monkeys (Macaca mulatta) across the menstrual cycle.

    PubMed

    Hunnell, Nathan A; Rockcastle, Nathan J; McCormick, Kristen N; Sinko, Laurel K; Sullivan, Elinor L; Cameron, Judy L

    2007-06-01

    Physical activity is an important physiological variable impacting on a number of systems in the body. In rodents and several species of domestic animals, levels of physical activity have been reported to vary across the estrous cycle; however, it is unclear whether such changes in activity occur in women and other primates across the menstrual cycle. To determine whether significant changes in activity occur over the menstrual cycle, we continuously measured physical activity in seven adult female rhesus monkeys by accelerometry over the course of one menstrual cycle. Monkeys were checked daily for menses, and daily blood samples were collected for measurement of reproductive hormones. All monkeys displayed ovulatory menstrual cycles, ranging from 23 to 31 days in length. There was a significant increase in estradiol from the early follicular phase to the day of ovulation (F(1.005,5.023) = 40.060, P = 0.001). However, there was no significant change in physical activity across the menstrual cycle (F(2,12) = 0.225, P = 0.802), with activity levels being similar in the early follicular phase, on the day of the preovulatory rise in estradiol and during the midluteal phase. Moreover, the physical activity of these monkeys was not outside the range of physical activity that we measured in 15 ovariectomized monkeys. We conclude that, in primates, physical activity does not change across the menstrual cycle and is not influenced by physiological changes in circulating estradiol. This finding will allow investigators to record physical activity in female primates without the concern of controlling for the phase of the menstrual cycle.

  18. 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.

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

    PubMed

    Poremba, Amy; Mishkin, Mortimer

    2007-07-01

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

  20. 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.

  1. 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.

  2. Acquisition Of Cocaine Self-Administration With Unsignaled Delayed Reinforcement In Rhesus Monkeys

    PubMed Central

    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 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

  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. Associations between early life experience, chronic HPA axis activity, and adult social rank in rhesus monkeys.

    PubMed

    Dettmer, Amanda M; Wooddell, Lauren J; Rosenberg, Kendra L; Kaburu, Stefano S K; Novak, Melinda A; Meyer, Jerrold S; Suomi, Stephen J

    2017-02-01

    Early life experience and socioeconomic status (SES) are well-established predictors of health outcomes in people. Both factors likely influence health outcomes via hypothalamic-pituitary-adrenal (HPA) axis regulation. However, it is unclear how early experience and HPA axis activity influence adult social status. We studied differentially reared female rhesus monkeys (Macaca mulatta, N = 90) as models to test the hypothesis that chronic HPA axis activity assessed via hair cortisol concentrations (HCCs) mediated the relationship between early life experience and adult social rank. We found that mother-peer-reared (MPR) monkeys acquired higher social ranks than either of the two nursery-reared (NR) groups (peer-reared, PR, or surrogate-peer-reared, SPR monkeys) (β = -0.07, t(89) = -2.16, p = 0.034). We also found that MPR HCCs were lower during the juvenile period at 18 months (F(2,25) = 3.49, p = 0.047). Furthermore, for MPR but not NR monkeys, changes in HCCs from 18 to 24 months (r(s) = -0.627, p = 0.039) and adult HCCs (r(s) = -0.321, p = 0.03) were negatively correlated with adult social rank. These findings suggest that chronic HPA axis regulation in juvenility, and perhaps in adulthood, may influence adult social status for primates that experience typical early rearing. However, early life adversity may result in dissociation between neuroendocrine stress regulation and adult social competence, which may be risk factors for adverse health outcomes.

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

    PubMed Central

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

    2016-01-01

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

  6. 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.

  7. Effect of genistein on steroid hormone production in the pregnant rhesus monkey.

    PubMed

    Harrison, R M; Phillippi, P P; Swan, K F; Henson, M C

    1999-10-01

    Genistein is a phytoestrogen found in soy beans. Phytoestrogens have been reported to cause reproductive problems in sheep and rats. This research was conducted to determine the effects of genistein fed to rhesus monkeys during pregnancy, with specific interest on fetal growth and steroidogenesis in the maternal-fetoplacental unit. Two groups of five monkeys each were selected in early stages of pregnancy. One group was administered genistein in a fruit treat each weekday until Cesarean section 10 days prior to term. The second, control group, received fruit treats without genistein. Maternal blood samples were collected on Tuesday and Friday of each week. At delivery, samples were collected from the maternal peripheral circulation, uterine veins, uterine-ovarian veins, and the fetal heart. Comparisons between control and genistein-treated monkeys revealed no differences in the maternal weight gained during pregnancy, or in fetal weights or placental weights at delivery. Serum was assayed by radioimmunoassay (RIA) for estradiol, progesterone, dehydroepiandrosterone sulfate (DHEA-S), and estrone. No significant differences (P > 0.05) were noted in progesterone or DHEA-S levels at delivery or during the pregnancy; however, estradiol levels were higher (P < 0.05) in the four areas studied at delivery and in the maternal blood with advancing gestation. Additionally, estrone levels tended to increase more rapidly (P = 0. 057) in the maternal blood of monkeys receiving genistein than in untreated controls, suggesting that genistein may stimulate the deconjugation of estrone in the gut, thus allowing its reabsorption into the peripheral circulation and conversion to estradiol.

  8. Importance of vpr for infection of rhesus monkeys with simian immunodeficiency virus.

    PubMed Central

    Lang, S M; Weeger, M; Stahl-Hennig, C; Coulibaly, C; Hunsmann, G; Müller, J; Müller-Hermelink, H; Fuchs, D; Wachter, H; Daniel, M M

    1993-01-01

    The importance of the vpr gene for simian immunodeficiency virus (SIV) replication, persistence, and disease progression was examined by using the infectious pathogenic molecular clone called SIVmac239. The ATG start codon of the vpr gene was converted to TTG by site-specific mutagenesis. The constructed Vpr- mutant virus is identical with the parental SIVmac239/nef-stop virus with the exception of this one nucleotide. These viruses replicated with similar kinetics and to similar extents in rhesus monkey lymphocyte cultures and in the human CEMX174 cell line. Five rhesus monkeys were inoculated with the Vpr- variant of SIVmac239/nef-stop, and two monkeys received SIVmac239/nef-stop as controls. Both controls showed reversion of the TAA stop signal in nef by 2 weeks postinfection, as has been observed previously. Reversion of the TAA stop codon in nef also occurred in the five monkeys that received the Vpr- variant, but reversion was delayed on average to about 4 weeks. Thus, the mutation in vpr appeared to delay the rapidity with which reversion occurred in the nef gene. Reversion of the TTG sequence in vpr to ATG was observed in three of the five test animals. Reversion in vpr was first observed in these three animals 4 to 8 weeks postinfection. No vpr revertants were found over the entire 66 weeks of observation in the other two test animals that received the vpr mutant. Antibodies to vpr developed in those three animals in which reversion of vpr was documented, but antibodies to vpr were not observed in the two animals in which reversion of vpr was not detected. Antibody responses to gag and to whole virus antigens were of similar strength in all seven animals. Both control animals and two of the test animals in which vpr reverted maintained high virus loads and developed progressive disease. Low virus burden and no disease have been observed in the two animals in which vpr did not revert and in the one animal in which vpr reversion was first detected only at 8

  9. 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.

  10. Effects of antipsychotic compounds in rhesus monkeys given a choice between cocaine and food.

    PubMed

    Woolverton, W L; Balster, R L

    1981-08-01

    Chlorpromazine (CPZ) and haloperidol (H) have been suggested as possible antagonists of the reinforcing effects of psychomotor stimulant drugs. To test this hypothesis in animals, four rhesus monkeys were trained in a preference procedure to choose between intravenous injections of cocaine or food presentation. Frequency of cocaine choice increased as unit dose of cocaine was increased. Continuous infusions of low or intermediate doses of CPZ or H either did not affect or increased the frequency of cocaine choice. Higher doses of CPZ or H completely suppressed responding for both reinforcers. Although ther appears to be a mutual antagonism of some of the effects of cocaine and these antipsychotic compounds, the results of the present experiment fail to support the hypothesis that the reinforcing effects of cocaine can be antagonized with CPZ or H.

  11. [Cellular composition of the lymph nodes of monkeys (rhesus macaque) under normal and experimental conditions].

    PubMed

    Rusina, A K

    1978-01-01

    By means of mathematical methods, quantitative and qualitative changes were studied in different structural components of the mesenteric (ileocecal) lymph nodes in normal monkeys (Macaca rhesus) and under per os administration of Salmonella typhi murium, streptomycin-dependent. Cellular composition was calculated in the cortical plateau, cortical (lymphoid) cords and in follicules. Average percent of every cell type was determined. Vaccine administration, was stated to inhibit cytopoiesis in the cortical plateau and in the follicules with light centers. An inverse correlation was noted between the content of small and medium size lymphocytes. Different reactivity of certain structural components in the lymph nodes was demonstrated. As a response to the vaccine administration, plasmocellular acidophilic and macrophagal reactions were most pronounced in the cortical (lymphoid) cords.

  12. 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.

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

    PubMed

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

    2017-01-01

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

  14. Gestational changes in the germinal matrix of the normal rhesus monkey fetus.

    PubMed

    Lenn, N J; Whitmore, L

    1985-01-01

    To explain the reported predisposition to germinal matrix hemorrhage in premature infants, pathogenetically important morphological features of the germinal matrix should be present in the 3rd trimester and rapidly change near term. Such features were sought in this study of the germinal matrix and its vasculature in normal rhesus monkey fetuses. The matrix cells, glia, ependyma, and capillaries showed no important structural changes during the 3rd trimester. The terminal vein tributaries were greatly enlarged by 148 days, but cellular and collagen support in their walls was minimal at this time. The latter features developed by the final days of gestation. These findings do not support a structural immaturity or specialization of the germinal matrix predisposing to germinal matrix hemorrhage. Our results, therefore, support the recent emphasis on physiological parameters in the pathogenesis and prevention of germinal matrix hemorrhage.

  15. [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.

  16. Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

    PubMed Central

    Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

    2014-01-01

    Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

  17. Great apes and rhesus monkeys as subjects for psychopharmacological studies of stimulants and depressants.

    PubMed

    Pieper, W A

    1976-09-01

    A group of experiments is described in which chimpanzees and orangutans are utilized as subjects in research projects designed to evaluate the effects of stimulant and depressant drugs on learning and performance. Efficiency of performance on a task which measures spaced responding was impaired when subjects smoked cigarettes containing delta9-tetrahydrocannabinol prior to testing. In a sequential learning task, these subjects also demonstrated reduced performance when stimulatn drugs were orally administered before testing. Depressant drugs did not produce comparable decrements in sequential learning performance. Physical and behavioral tolerance and dependence on ethanol were investigated in rhesus monkey subjects using a variety of experimental procedures, including forced oral acceptance, intragastric intubation, intravenous infusion, and conditioned voluntary oral acceptance.

  18. Cortisol in Neonatal Mother's Milk Predicts Later Infant Social and Cognitive Functioning in Rhesus Monkeys.

    PubMed

    Dettmer, Amanda M; Murphy, Ashley M; Guitarra, Denisse; Slonecker, Emily; Suomi, Stephen J; Rosenberg, Kendra L; Novak, Melinda A; Meyer, Jerrold S; Hinde, Katie

    2017-03-29

    Milk provides not only the building blocks for somatic development but also the hormonal signals that contribute to the biopsychological organization of the infant. Among mammals, glucocorticoids (GCs) in mother's milk have been associated with infant temperament. This study extended prior work to investigate rhesus monkey (Macaca mulatta) mother-infant dyads (N = 34) from birth through 8 months postpartum. Regression analysis revealed that cortisol concentrations in milk during the neonatal period predicted impulsivity on a cognitive task, but not global social behaviors, months later. During this time period, sex-differentiated social behavior emerged. For female infants, milk cortisol concentrations predicted total frequency of play. Collectively, these findings support and extend the "lactational programming" hypothesis on the impact of maternal-origin hormones ingested via milk.

  19. 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.

  20. 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

  1. 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.

  2. 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

  3. Endocrine and neurochemical effects of 3,4-methylenedioxymethamphetamine and its stereoisomers in rhesus monkeys.

    PubMed

    Murnane, K S; Fantegrossi, W E; Godfrey, J R; Banks, M L; Howell, L L

    2010-08-01

    3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative that elicits complex biological effects in humans. One plausible mechanism for this phenomenon is that racemic MDMA is composed of two stereoisomers that exhibit qualitatively different pharmacological effects. In support of this, studies have shown that R(-)-MDMA tends to have hallucinogen-like effects, whereas S(+)-MDMA tends to have psychomotor stimulant-like effects. However, relatively little is known about whether these stereoisomers engender different endocrine and neurochemical effects. In the present study, the endocrine and neurochemical effects of each stereoisomer and the racemate were assessed in four rhesus monkeys after intravenous delivery at doses (1-3 mg/kg) that approximated voluntary self-administration by rhesus monkeys and human recreational users. Specifically, fluorescence-based enzyme-linked immunosorbent assay was used to assess plasma prolactin concentrations, and in vivo microdialysis was used to assess extracellular dopamine and serotonin concentrations in the dorsal striatum. R(-)-MDMA, but not S(+)-MDMA, significantly increased plasma prolactin levels and the effects of S,R(+/-)-MDMA were intermediate to each of its component stereoisomers. Although S(+)-MDMA did not alter prolactin levels, it did significantly increase extracellular serotonin concentrations. In addition, S(+)-MDMA, but not R(-)-MDMA, significantly increased dopamine concentrations. Furthermore, as in the prolactin experiment, the effects of the racemate were intermediate to each of the stereoisomers. These studies demonstrate the stereoisomers of MDMA engender qualitatively different endocrine and neurochemical effects, strengthening the inference that differences in these stereoisomers might be the mechanism producing the complex biological effects of the racemic mixture of MDMA in humans.

  4. Rhesus monkey sperm cryopreservation with TEST-yolk extender in the absence of permeable cryoprotectant.

    PubMed

    Dong, Qiaoxiang; Correa, Liane M; VandeVoort, Catherine A

    2009-02-01

    Recently, there has been increased interest in ultra-rapid freezing with mammalian spermatozoa, especially for vitrification in the absence of cryoprotectants. Sperm cryopreservation in non-human primates has been successful, but the use of frozen-thawed sperm in standard artificial insemination (AI) remains difficult, and removal of permeable cryoprotectant may offer opportunities for increased AI success. The present study intended to explore the possibility of freezing rhesus monkey sperm in the absence of permeable cryoprotectants. Specifically, we evaluated various factors such as presence or absence of egg yolk, the percentage of egg yolk in the extenders, and the effect of cooling and thawing rate on the success of freezing without permeable cryoprotectants. Findings revealed that freezing with TEST in the absence of egg yolk offers little protection (<15% post-thaw motility). Egg yolk of 40% or more in TEST resulted in decreased motility, while egg yolk in the range of 20-30% yielded the most motile sperm. Cooling at a slow rate (29 degrees C/min) reduced post-thaw motility significantly for samples frozen with TEST-yolk alone, but had no effect for controls in the presence of glycerol. Similarly, slow thawing in room temperature air is detrimental for freezing without permeable cryoprotectant (<2% motility). In addition to motility, the ability of sperm to capacitate based on an increase in intracellular calcium levels upon activation with cAMP and caffeine suggested no difference between fresh and frozen-thawed motile sperm, regardless of treatment. In summary, the present study demonstrates that ejaculated and epididymal sperm from rhesus monkeys can be cryopreserved with TEST-yolk (20%) in the absence of permeable cryoprotectant when samples were loaded in a standard 0.25-mL straw, cooled rapidly in liquid nitrogen vapor at 220 degrees C/min, and thawed rapidly in a 37 degrees C water bath. This study also represents the first success of freezing

  5. Neurotoxin-Induced Catecholaminergic Loss in the Colonic Myenteric Plexus of Rhesus Monkeys

    PubMed Central

    Shultz, Jeanette M; Resnikoff, Henry; Bondarenko, Viktorya; Joers, Valerie; Mejia, Andres; Simmons, Heather; Emborg, Marina E

    2017-01-01

    Objective Constipation is a common non-motor symptom of Parkinson’s disease (PD). Although pathology of the enteric nervous system (ENS) has been associated with constipation in PD, the contribution of catecholaminergic neurodegeneration to this symptom is currently debated. The goal of this study was to assess the effects of the neurotoxin 6-hydroxydopamine (6-OHDA) on the colonic myenteric plexus and shed light on the role of catecholaminergic innervation in gastrointestinal (GI) function. Methods Proximal colon tissue from 6-OHDA-treated (n=5) and age-matched control (n=5) rhesus monkeys was immunostained and quantified using ImageJ software. All animals underwent routine daily feces monitoring to assess for constipation or other GI dysfunction. Results Quantification of tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AADC)-immunoreactivity (-ir) revealed significant reduction in myenteric ganglia of 6-OHDA-treated animals compared to controls (TH-ir: 87.8%, P<0.0001; AADC-ir: 61.7% P=0.0034). Analysis of pan-neuronal markers (PGP9.5, HuC/D), other neurochemical phenotypes (VIP, nNOS), PD-associated pathology proteins (α-synuclein, phosphorylated α-synuclein), glial marker GFAP and neuroinflammation and oxidative stress (HLA-DR, CD45, Nitrotyrosine) did not show significant differences. Monitoring of feces revealed frequent (>30% days) soft stool or diarrhea in 2 of the 5 6-OHDA-treated animals and 0 of the 5 control animals during the 2 months prior to necropsy, with no animals exhibiting signs of constipation. Conclusion Systemic administration of 6-OHDA to rhesus monkeys significantly reduced catecholaminergic expression in the colonic myenteric plexus without inducing constipation. These findings support the concept that ENS catecholaminergic loss is not responsible for constipation in PD. PMID:28090391

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

    PubMed

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

    2017-01-01

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

  7. 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.

  8. 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.

  9. Pharmacokinetics of spiramycin in the rhesus monkey: transplacental passage and distribution in tissue in the fetus.

    PubMed Central

    Schoondermark-Van de Ven, E; Galama, J; Camps, W; Vree, T; Russel, F; Meuwissen, J; Melchers, W

    1994-01-01

    Transplacental transfer of spiramycin was investigated in a rhesus monkey model to study whether the antibiotic reaches therapeutic levels in the fetus. Spiramycin concentrations were measured by bioassay and high-performance liquid chromatography. Pharmacokinetic parameters were determined for bioactive spiramycin as measured by the bioassay. Pharmacokinetic pilot studies showed that spiramycin distribution follows a two-compartment model in rhesus monkeys. Following a single intravenous dose of 50 or 250 mg, dose-dependent kinetics were observed. At a dose of 50 mg, 10% of the dose was excreted unchanged in the urine. At the higher dose of 250 mg, an oliguric effect was observed. Spiramycin concentrations in fetal serum were measured over time while the maternal concentration was maintained at a constant level. During a 5-h experiment, a maximum fetal-maternal serum ratio of 0.27 was found. In three fetuses, concentrations in serum and tissue were measured following intravenous administration of 50 mg of spiramycin twice daily to the mother for at least 7 days. The fetal-maternal serum ratios were found to be 0.4 to 0.58 after intravenous administration of the final dose of 50 mg to the mother. It appeared that spiramycin accumulated in the soft tissues, especially in the liver and spleen, of both the mother and the fetus. The concentration in placental tissue appeared to be 10 to 20 times that of the concentration in fetal serum. The concentration of spiramycin in amniotic fluid was about five times higher than the concentration in fetal serum. Another important observation was that absolutely no spiramycin was found in the brain. PMID:7810999

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

    PubMed Central

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

    2012-01-01

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

  11. Prenatal stress, moderate fetal alcohol, and dopamine system function in rhesus monkeys.

    PubMed

    Roberts, A D; Moore, C F; DeJesus, O T; Barnhart, T E; Larson, J A; Mukherjee, J; Nickles, R J; Schueller, M J; Shelton, S E; Schneider, M L

    2004-01-01

    This study examined the striatal dopamine system integrity and associated behavior in 5- to 7-year-old rhesus monkeys born from mothers that experienced stress and/or consumed moderate levels of alcohol during pregnancy. Thirty-one young adult rhesus monkeys were derived from females randomly assigned to one of four groups: (1) control group that consumed isocaloric sucrose solution throughout gestation; (2) stress group that experienced prenatal stress (10-min removal from home cage and exposure to three random loud noise bursts, gestational days 90 through 145); (3) alcohol group that consumed alcohol (0.6 g/kg/day) throughout gestation; or (4) combined alcohol plus stress group that received both treatments. The subjects were assessed for striatal dopamine system function using positron emission tomography (PET), in which the dopamine (DA)-rich striatum was evaluated in separate scans for the trapping of [(18)F]-Fallypride (FAL) and 6-[(18)F]fluoro-m-tyrosine (FMT) to assess dopamine D2 receptor binding potential (BP) and DA synthesis via dopa decarboxylase activity, respectively. Subjects were previously assessed for non-matching-to-sample (NMS) task acquisition, with ratings of behavioral inhibition, stereotypies, and activity made after each NMS testing session. Subjects from prenatal stress conditions (Groups 2 and 4) showed an increase in the ratio of striatal dopamine D2 receptor BP and DA synthesis compared to controls (Group 1). An increase in the radiotracer distribution volume ratios (DVRs), which is used to evaluate the balance between striatal DA synthesis and receptor availability, respectively, was significantly correlated with less behavioral inhibition. The latter supports a hypothesis linking striatal function to behavioral inhibitory control.

  12. Metric characteristics of the canine dental complex in prenatally androgenized female rhesus monkeys (Macaca mulatta).

    PubMed

    Zingeser, M R; Phoenix, C H

    1978-08-01

    Permanent maxillary canine teeth (C1) are appreciably larger in males than in females in most nonhominid Anthropoidea. Mandibular canines (C1) and mandibular first premolars (P3), against which C1 are sharpened in honing behavior, reflect commensurate sexual dimorphism. These three teeth constitute the canine dental complex. The canine complex crown metrics of seven mature genetically female rhesus Macaques, androgenized by prenatal exposure to testosterone propionate, were compared with a control sample (N = 12) for evidence of masculinization. The C1 and C1 were measured for clinical crown lengths (L) and mesiodistal and buccolingual widths. The functionally significant and highly dimorphic honing dimensions (HD), which approximate the honing surfaces of P3, were noted. In t-test comparisons, the C1 L and P3 HD in androgenized monkeys were significantly larger than those of the control group (P less than 0.05). Identical results were obtained with White's nonparametric ranking technique. Standardized lateral skull radiographs showing earlier dental formative stages were available for five of the seven animals, and these were compared with radiographs of control skulls. The developing C1 were longer and wider than in the controls. This was not reflected in the crown metrics of mature animals because of marked dental attrition. We concluded that androgens can masculinize the female rhesus canine complex, if given during critical periods of prenatal development. We hypothesize that genes encoding the male canine complex are normally activated by endogenous fetal androgens during such critical periods.

  13. 5-androstenediol improves survival in clinically unsupported rhesus monkeys with radiation-induced myelosuppression.

    PubMed

    Stickney, Dwight R; Dowding, Charles; Authier, Simon; Garsd, Armando; Onizuka-Handa, Nanette; Reading, Christopher; Frincke, James M

    2007-04-01

    We previously reported that five daily intramuscular doses of 5-androstenediol (AED), a naturally occurring adrenal steroid hormone, stimulated multilineage recovery of bone marrow in rhesus monkeys with radiation-induced myelosuppression after 4.0 Gy total body irradiation (TBI). Here we report the effect of AED on the survival of eighty rhesus macaques that received a 6.0 Gy dose of TBI in four sequential pilot studies. The drug was administered intramuscularly, based on body weight, 2-4 h after irradiation and continued once daily for a total of five injections. No clinical support in the form of antibiotics or transfusions was given to the animals at any time during the study. Five of the 40 (12.5%) treated animals died, compared to 13 of 40 (32.5%) of the animals in the control group (p=0.032). The combination of accumulated days of thrombocytopenia (<20,000 platelets/microL) up to day 14 (before the first death) together with treatment, accurately predicts mortality (p<0.001). The compound significantly reduced the duration of thrombocytopenia and neutropenia (p<0.01). The accumulation of days of neutropenia (ANC<500 cells/microL) up to day 14 plays no major role in predicting death. AED shows significant activity in irradiated primates with acute hematopoietic radiation syndrome.

  14. 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.

  15. 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.

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

    PubMed

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

    1997-03-01

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

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

    PubMed

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

    2014-01-01

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

  18. Visual Nesting of Stimuli Affects Rhesus Monkeys' (Macaca mulatta) Quantity Judgments in a Bisection Task

    PubMed Central

    Beran, Michael J.; Parrish, Audrey E.

    2013-01-01

    Nonhuman animals are highly proficient at judging relative quantities presented in a variety of formats including visual, auditory, and even cross modal formats. Performance typically is constrained by the ratio between sets, as would be expected under Weber's Law, and as is described in the Approximate Number System (ANS) hypothesis. In most cases, tests are designed to avoid any perceptual confusion for animals regarding the stimulus sets, but despite this, animals show some of the perceptual biases that humans show based on organization of stimuli. Here, we demonstrate an additional perceptual bias that emerges from the illusion of nested sets. When arrays of circles were presented on a computer screen and were to be classified as larger than or as smaller than an established central value, rhesus monkeys (Macaca mulatta) underestimated quantities when circles were nested within each other. This matched a previous report with adult humans (Chesney & Gelman, 2012), indicating that macaques, like humans, show the pattern of biased perception predicted by ANS estimation. Although some macaques overcame this perceptual bias demonstrating that they could come to view nested stimuli as individual elements to be included in the estimates of quantity used for classifying arrays, the majority of the monkeys showed the bias of underestimating nested arrays throughout the experiment. PMID:23709063

  19. Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys.

    PubMed

    Borducchi, Erica N; Cabral, Crystal; Stephenson, Kathryn E; Liu, Jinyan; Abbink, Peter; Ng'ang'a, David; Nkolola, Joseph P; Brinkman, Amanda L; Peter, Lauren; Lee, Benjamin C; Jimenez, Jessica; Jetton, David; Mondesir, Jade; Mojta, Shanell; Chandrashekar, Abishek; Molloy, Katherine; Alter, Galit; Gerold, Jeffrey M; Hill, Alison L; Lewis, Mark G; Pau, Maria G; Schuitemaker, Hanneke; Hesselgesser, Joseph; Geleziunas, Romas; Kim, Jerome H; Robb, Merlin L; Michael, Nelson L; Barouch, Dan H

    2016-12-08

    The development of immunologic interventions that can target the viral reservoir in HIV-1-infected individuals is a major goal of HIV-1 research. However, little evidence exists that the viral reservoir can be sufficiently targeted to improve virologic control following discontinuation of antiretroviral therapy. Here we show that therapeutic vaccination with Ad26/MVA (recombinant adenovirus serotype 26 (Ad26) prime, modified vaccinia Ankara (MVA) boost) and stimulation of TLR7 (Toll-like receptor 7) improves virologic control and delays viral rebound following discontinuation of antiretroviral therapy in SIV-infected rhesus monkeys that began antiretroviral therapy during acute infection. Therapeutic vaccination with Ad26/MVA resulted in a marked increase in the magnitude and breadth of SIV-specific cellular immune responses in virologically suppressed, SIV-infected monkeys. TLR7 agonist administration led to innate immune stimulation and cellular immune activation. The combination of Ad26/MVA vaccination and TLR7 stimulation resulted in decreased levels of viral DNA in lymph nodes and peripheral blood, and improved virologic control and delayed viral rebound following discontinuation of antiretroviral therapy. The breadth of cellular immune responses correlated inversely with set point viral loads and correlated directly with time to viral rebound. These data demonstrate the potential of therapeutic vaccination combined with innate immune stimulation as a strategy aimed at a functional cure for HIV-1 infection.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. Calorie Restriction Reduces the Influence of Glucoregulatory Dysfunction on Regional Brain Volume in Aged Rhesus Monkeys

    PubMed Central

    Willette, Auriel A.; Bendlin, Barbara B.; Colman, Ricki J.; Kastman, Erik K.; Field, Aaron S.; Alexander, Andrew L.; Sridharan, Aadhavi; Allison, David B.; Anderson, Rozalyn; Voytko, Mary-Lou; Kemnitz, Joseph W.; Weindruch, Richard H.; Johnson, Sterling C.

    2012-01-01

    Insulin signaling dysregulation is related to neural atrophy in hippocampus and other areas affected by neurovascular and neurodegenerative disorders. It is not known if long-term calorie restriction (CR) can ameliorate this relationship through improved insulin signaling or if such an effect might influence task learning and performance. To model this hypothesis, magnetic resonance imaging was conducted on 27 CR and 17 control rhesus monkeys aged 19–31 years from a longitudinal study. Voxel-based regression analyses were used to associate insulin sensitivity with brain volume and microstructure cross-sectionally. Monkey motor assessment panel (mMAP) performance was used as a measure of task performance. CR improved glucoregulation parameters and related indices. Higher insulin sensitivity predicted more gray matter in parietal and frontal cortices across groups. An insulin sensitivity × dietary condition interaction indicated that CR animals had more gray matter in hippocampus and other areas per unit increase relative to controls, suggesting a beneficial effect. Finally, bilateral hippocampal volume adjusted by insulin sensitivity, but not volume itself, was significantly associated with mMAP learning and performance. These results suggest that CR improves glucose regulation and may positively influence specific brain regions and at least motor task performance. Additional studies are warranted to validate these relationships. PMID:22415875

  6. 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.

  7. Valproic acid developmental toxicity and pharmacokinetics in the rhesus monkey: an interspecies comparison.

    PubMed

    Hendrickx, A G; Nau, H; Binkerd, P; Rowland, J M; Rowland, J R; Cukierski, M J; Cukierski, M A

    1988-10-01

    This study was undertaken to assess the developmental toxicity and drug distributional and metabolic characteristics of prenatal valproic acid (VPA) exposure in rhesus monkeys. Oral administration of 20-600 mg/kg/day VPA (approximately 1-15 X human therapeutic dose) to 33 animals on variable gestational days (GD) during organogenesis resulted in dose-dependent developmental toxicity manifested as increased embryo/fetal mortality, intrauterine growth retardation, and craniofacial and skeletal defects. Biphasic plasma elimination curves were observed for total and free VPA on the first (GD 21) and last (GD 50) days of treatment in the 100- and 200-mg/kg/day dose groups. VPA exhibited dose-independent elimination kinetics at the plasma concentrations observed in this study. There was no significant change in pharmacokinetic parameters (maternal plasma elimination rate, area under the curve, peak plasma concentration) between the first and last days of treatment at either dose level. Placental transfer studies indicated that embryos were exposed to half the free VPA concentrations present in maternal plasma on GD 37. Comparisons of interspecies sensitivity to VPA-induced developmental toxicity in the mouse, rat, monkey, and man are made.

  8. Familial hypercholesterolemia in a rhesus monkey pedigree: molecular basis of low density lipoprotein receptor deficiency.

    PubMed Central

    Hummel, M; Li, Z G; Pfaffinger, D; Neven, L; Scanu, A M

    1990-01-01

    We have recently identified a family of rhesus monkeys with members exhibiting a spontaneous hypercholesterolemia associated with a low density lipoprotein receptor (LDLR) deficiency. By using the polymerase chain reaction, we now show that the affected monkeys are heterozygous for a nonsense mutation in exon 6 of the LDLR gene. This mutation changes the sequence of the codon for amino acid 284 (tryptophan) from TGG to TAG, thereby generating a nonsense codon potentially resulting in a truncated 283-amino acid protein, which needs documentation, however. This G----A mutation also creates a site for the restriction endonuclease Spe I. Using this site as a marker for this nonsense mutation, we have shown that the mutation is present in all of the affected members of the pedigree and absent in unaffected members and that the mutation segregates with the phenotype of spontaneous hypercholesterolemia through three generations. Quantitative analyses of RNA obtained from liver biopsies show that the abundance of the LDLR RNA is also reduced by about 50%. Thus, we have identified a primate model for human familial hypercholesterolemia which will be useful for studying the relationship between the LDLR and lipoprotein metabolism and for assessing the efficacy of diets and drugs in the treatment of human familial hypercholesterolemia. Images PMID:2326270

  9. 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.

  10. 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.

  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. Discriminative stimulus effects of benzodiazepine (BZ)(1) receptor-selective ligands in rhesus monkeys.

    PubMed

    McMahon, Lance R; Gerak, Lisa R; Carter, Lawrence; Ma, Chunrong; Cook, James M; France, Charles P

    2002-02-01

    Drug discrimination was used to examine the effects of benzodiazepine (BZ)(1) receptor-selective ligands in rhesus monkeys. In diazepam-treated (5.6 mg/kg, p.o.) monkeys discriminating the nonselective BZ antagonist flumazenil (0.32 mg/kg, s.c.), the BZ(1)-selective antagonist beta-carboline-3-carboxylate-t-butyl ester (beta-CCt) substituted for flumazenil. The onset of action of beta-CCt was delayed with a dose of 5.6 mg/kg beta-CCt substituting for flumazenil 2 h after injection. In monkeys discriminating the nonselective BZ agonist midazolam (0.56 mg/kg, s.c.), the BZ(1)-selective agonists zaleplon (ED(50) = 0.78 mg/kg) and zolpidem (ED(50) = 1.73 mg/kg) substituted for midazolam. The discriminative stimulus effects of midazolam, zaleplon, and zolpidem were antagonized by beta-CCt (1.0-5.6 mg/kg, s.c.), and the effects of zaleplon and zolpidem were also antagonized by flumazenil (0.01-0.32 mg/kg, s.c.). Schild analyses supported the notion of a simple, competitive interaction between beta-CCt and midazolam (slope = -1.08; apparent pA(2) = 5.41) or zaleplon (slope = -1.57; apparent pA(2) = 5.49) and not between beta-CCt and zolpidem. Schild analyses also were consistent with a simple, competitive interaction between flumazenil and zaleplon (slope = -1.03; apparent pA(2) = 7.45) or zolpidem (slope = -1.11; apparent pA(2) = 7.63). These results suggest that the same BZ receptor subtype(s) mediate(s) the effects of midazolam, zolpidem, and zaleplon under these conditions and that selective binding of BZ ligands does not necessarily confer selective effects in vivo.

  13. 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.

  14. 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

    2016-11-05

    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.

  15. 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.

  16. 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.

  17. Nalfurafine hydrochloride, a selective κ opioid receptor agonist, has no reinforcing effect on intravenous self-administration in rhesus monkeys.

    PubMed

    Nakao, Kaoru; Hirakata, Mikito; Miyamoto, Yohei; Kainoh, Mie; Wakasa, Yoshio; Yanagita, Tomoji

    2016-01-01

    Nalfurafine hydrochloride [(E)-N-[17-(cyclopropylmethyl)-4,5α-epoxy-3,14-dihydroxymorphinan-6β-yl]-3-(furan-3-yl)-N-methylprop-2-enamide monohydrochloride; nalfurafine] is used in Japan as an antipruritic for the treatment of intractable pruritus in patients undergoing hemodialysis or with chronic liver disease. It is a potent and selective agonist at the κ opioid receptor, but also has weak and partial agonist activity at μ opioid receptors. Opioids, especially those acting at μ receptors, carry a risk of abuse. This is an important factor in the consideration of therapeutic risk vs. benefit in clinical use and the potential for misuse as a public health problem. It is therefore necessary to carefully evaluate the reinforcing effects of nalfurafine. To this end, we investigated intravenous self-administration of nalfurafine in rhesus monkeys. The number of self-administration of nalfurafine at doses of 0.0625, 0.125 and 0.25 μg/kg/infusion was not higher than that of saline in rhesus monkeys that frequently self-administered pentazocine (0.25 mg/kg/infusion). These results indicate that nalfurafine has no reinforcing effect in rhesus monkeys in the intravenous self-administration paradigm.

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

    PubMed

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

    2016-03-02

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

  19. An enzyme-linked immunosorbent assay to study human relaxin in human pregnancy and in pregnant rhesus monkeys.

    PubMed

    Lucas, C; Bald, L N; Martin, M C; Jaffe, R B; Drolet, D W; Mora-Worms, M; Bennett, G; Chen, A B; Johnston, P D

    1989-03-01

    A sensitive and specific double-antibody enzyme-linked immunoassay, using a synthetic analogue of human relaxin for standard and immunogen, was developed for the measurement of human relaxin (hRLX) in serum and plasma. No cross-reactivity was observed for human insulin, human insulin-like growth factor-I, hGH, human chorionic gonadotropin, hFSH, hLH or human prolactin. The assay was used to monitor RLX concentrations in samples from men, non-pregnant and pregnant women, and in pregnant rhesus monkeys infused with hRLX. RLX was not detected in serum from men nor from non-pregnant women, while a concentration of 600 ng/l was measured in pooled sera from two pregnant women (pregnancies achieved by in-vitro fertilization). Immunoreactive RLX (1.1 micrograms/g) was found in human corpora lutea taken from ectopic pregnancies at 7 weeks. In an experiment with a pregnant rhesus monkey infused with human RLX analogue, less than 1.5% of the maternal concentration was measured in the fetal circulation. Even though preliminary, these data suggest a low level of transfer of human analogue relaxin across the placenta in a rhesus monkey. Further studies of the physiology of RLX in human pregnancy will be facilitated by the availability of this immunoassay.

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

    PubMed

    Khachaturian, Mark Haig

    2010-01-01

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

  1. 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.

  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 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

  3. 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.

  4. Rhesus monkeys (Macaca mulatta) do recognize themselves in the mirror: implications for the evolution of self-recognition.

    PubMed

    Rajala, Abigail Z; Reininger, Katharine R; Lancaster, Kimberly M; Populin, Luis C

    2010-09-29

    Self-recognition in front of a mirror is used as an indicator of self-awareness. Along with humans, some chimpanzees and orangutans have been shown to be self-aware using the mark test. Monkeys are conspicuously absent from this list because they fail the mark test and show persistent signs of social responses to mirrors despite prolonged exposure, which has been interpreted as evidence of a cognitive divide between hominoids and other species. In stark contrast with those reports, the rhesus monkeys in this study, who had been prepared for electrophysiological recordings with a head implant, showed consistent self-directed behaviors in front of the mirror and showed social responses that subsided quickly during the first experimental session. The self-directed behaviors, which were performed in front of the mirror and did not take place in its absence, included extensive observation of the implant and genital areas that cannot be observed directly without a mirror. We hypothesize that the head implant, a most salient mark, prompted the monkeys to overcome gaze aversion inhibition or lack of interest in order to look and examine themselves in front of the mirror. The results of this study demonstrate that rhesus monkeys do recognize themselves in the mirror and, therefore, have some form of self-awareness. Accordingly, instead of a cognitive divide, they support the notion of an evolutionary continuity of mental functions.

  5. 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

  6. Immunohistochemical Localization of AMPA Type Glutamate Receptor Subunits in the Striatum of Rhesus Monkey

    PubMed Central

    Deng, Yun-Ping; Shelby, Evan; Reiner, Anton J.

    2010-01-01

    Corticostriatal and thalamostriatal projections utilize glutamate as their neurotransmitter. Their influence on striatum is mediated, in part, by ionotropic AMPA-type glutamate receptors, which are heteromers composed of GluR1-4 subunits. While the cellular localization of AMPA-type subunits in the basal ganglia has been well characterized in rodents, the cellular localization of AMPA subunits in primate basal ganglia is not. We thus carried out immunohistochemical studies of GluR1-4 distribution in rhesus monkey basal ganglia in conjunction with characterization of each major neuron type. In striatum, about 65% of striatal neurons immunolabeled for GluR1, 75%-79% immunolabeled for GluR2 or GluR2/3, and only 2.5% possessed GluR4. All neurons the large size of cholinergic interneurons (mean diameter 26.1μm) were moderately labeled for GluR1, while all neurons in the size range of parvalbuminergic interneurons (mean diameter 13.8μm) were intensely rich in GluR1. Additionally, somewhat more than half of neurons in the size range of projection neurons (mean diameter 11.6μm) immunolabeled for GluR1, and about one third of these were very rich in GluR1. About half of neurons the size of cholinergic interneurons were immunolabeled for GluR2, and the remainder of the neurons that were immunolabeled for GluR2 coincided with projection neurons in size and shape (GluR2 diameter=10.7μm), indicating that the vast majority of striatal projection neurons possess immunodectible GluR2. Similar results were observed with GluR2/3 immunolabeling. Half of the neurons the size of cholinergic interneurons immunolabeled for GluR4 and seemingly all neurons in the size range of parvalbuminergic interneurons possessed GluR4. These results indicate that AMPA receptor subunit combinations for striatal projection neurons in rhesus monkey are similar to those for the corresponding neuron types in rodents, and thus their AMPA responses to glutamate likely to be similar to those demonstrated

  7. 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.

  8. Microglia activation and phagocytosis: relationship with aging and cognitive impairment in the rhesus monkey.

    PubMed

    Shobin, Eli; Bowley, Michael P; Estrada, Larissa I; Heyworth, Nadine C; Orczykowski, Mary E; Eldridge, Sherri A; Calderazzo, Samantha M; Mortazavi, Farzad; Moore, Tara L; Rosene, Douglas L

    2017-02-25

    While cognitive decline is observed in the normal aging monkey, neurons are not lost with age. Instead, frontal white matter is lost as myelin degenerates and both correlate with age-related cognitive decline. As age-related myelin damage increases, there should be an increase in clearance of damaged myelin by microglial phagocytosis. In this study, brains of behaviorally tested rhesus monkeys were assessed using unbiased stereology to quantify the density of activated microglia (LN3 antibody positive) and phagocytic microglia (galectin-3 (Gal-3) antibody positive) in three white matter regions: the corpus callosum, cingulum bundle (CGB), and frontal white matter (FWM). LN3 cell density was significantly increased in the CGB, whereas Gal-3 cell density was significantly increased in all regions. Increases in Gal-3 cell density in the FWM were associated with cognitive impairment. In the FWM of old animals, Gal-3-positive microglia were classified by morphological subtype as ramified, hypertrophic, or amoeboid. The densities of hypertrophic and amoeboid microglia significantly correlated with cognitive impairment. Finally, microglia were double-labeled with LN3 and Gal-3 showing that 91% of Gal-3 cells were also LN3 positive, thus expressing an "activated" phenotype. Furthermore, 15% of all double-labeled cells formed phagocytic cups. Overall, these results suggest that microglia become activated in white matter with age where the majority express a phagocytic phenotype. We hypothesize that age-related phagocytic activation of microglia is a response to accumulating myelin pathology. The association of Gal-3 in the FWM with cognitive impairment may reflect regional differences in damage or dysfunction of normal clearance mechanisms.

  9. Abstinence from Chronic Cocaine Self-Administration Alters Striatal Dopamine Systems in Rhesus Monkeys

    PubMed Central

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

    2013-01-01

    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. [3H]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 [3H]raclopride binding to DA D2 receptors was not different between groups. [3H]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

  10. 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

  11. A behavioral taxonomy of loneliness in humans and rhesus monkeys (Macaca mulatta).

    PubMed

    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

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

    PubMed

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

    1986-01-01

    The time-course of the metabolic fate of [14C]doxylamine was determined after the p.o. administration of 13 mg/kg doxylamine succinate as Bendectin plus [14C]doxylamine succinate to the rhesus monkey. Urine and plasma samples were analyzed by reversed-phase high performance liquid chromatography (HPLC), chemical derivatization, and mass spectrometry. The cumulative 48-hr urinary metabolic profile contained 81% of the administered radiolabeled dose and consisted of at least six radiolabeled peaks. They were peak 1: unknown polar metabolites (8% of dose); peak 2: 2-[1-phenyl-1-(2-pyridinyl)ethoxy] acetic acid, 1-[1-phenyl-1(2-pyridinyl)ethoxy] methanol, and another minor metabolite(s) (31%); peak 3: doxylamine-N-oxide (1%); peak 4a: N,N-didesmethyldoxylamine (17%); peak 4b: doxylamine (4%); and peak 5: N-desmethyldoxylamine (20%). The plasma metabolic profile was the same as the urinary profile except for the absence of doxylamine-N-oxide. The maximum plasma concentrations and elapsed time to attain these concentrations were as follows. Peak 1: 540 ng/mL, 4 hr; peak 2: 1700 ng/mL, 1 hr; peak 4a: 430 ng/mL, 4 hr; peak 4b: 930 ng/mL, 2 hr; and peak 5: 790 ng/mL, 2 hr. These data suggest that in the monkey, doxylamine metabolism follows at least four pathways: a minor pathway to the N-oxide; a minor pathway to unknown polar metabolites; a major pathway to mono- and didesmethyldoxylamine via successive N-demethylation; and a major pathway to side-chain cleavage products (peak 2) via direct side-chain oxidation and/or deamination.

  13. 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.

  14. 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.

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

    PubMed

    Kusmierek, Pawel; Rauschecker, Josef P

    2009-09-01

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

  16. Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys.

    PubMed

    Bello, Nicholas T; Kemm, Matthew H; Moran, Timothy H

    2008-07-01

    Amylinergic mechanisms are believed to be involved in the control of appetite. This study examined the effects of the amylin agonist, salmon calcitonin, on food intake and meal patterns in adult male rhesus monkeys. Fifteen minutes before the onset of their 6-h daily feeding period, monkeys received intramuscular injections of various doses of salmon calcitonin (0.032, 0.056, 0.1, 0.32, and 1 microg/kg) or saline. Salmon calcitonin dose dependently reduced total daily and hourly food intake, with significant decreases at the 0.1, 0.32, and 1 microg/kg doses. Daily food intake was reduced by approximately 35%, 62%, and 96%, at these doses, respectively. An analysis of meal patterns revealed that size of the first meal was significantly reduced across the dose range of 0.056 to 1 microg/kg, while average meal size was reduced with the 0.32 and 1 microg/kg doses. Meal number was only affected at the 1 microg/kg dose. Repeated 5-day administration of the 0.1 microg/kg dose resulted in a reduction in daily food intake only on injection day 2, while significant reductions in food intake were observed on all five injection days with a 0.32 microg/kg dose. Daily food intake was also reduced for 1 day after the termination of the 5-day injections of the 0.32 microg/kg salmon calcitonin dose. These sustained reductions in intake were expressed through decreases in meal size. These data demonstrate that salmon calcitonin acutely and consistently decreases food intake mainly through reductions in meal sizes in nonhuman primates.

  17. Neurotoxic lesions of the medial mediodorsal nucleus of the thalamus disrupt reinforcer devaluation effects in rhesus monkeys.

    PubMed

    Mitchell, Anna S; Browning, Philip G F; Baxter, Mark G

    2007-10-17

    The mediodorsal thalamus is a major input to the prefrontal cortex and is thought to modulate cognitive functions of the prefrontal cortex. Damage to the medial, magnocellular part of the mediodorsal thalamus (MDmc) impairs cognitive functions dependent on prefrontal cortex, including memory. The contribution of MDmc to other aspects of cognition dependent on prefrontal cortex has not been determined. The ability of monkeys to adjust their choice behavior in response to changes in reinforcer value, a capacity impaired by lesions of orbital prefrontal cortex, can be tested in a reinforcer devaluation paradigm. In the present study, rhesus monkeys with bilateral neurotoxic MDmc lesions were tested in the devaluation procedure. Monkeys learned visual discrimination problems in which each rewarded object is reliably paired with one of two different food rewards and then were given choices between pairs of rewarded objects, one associated with each food. Selective satiation of one of the food rewards reduces choices of objects associated with that food in normal monkeys. Monkeys with bilateral neurotoxic lesions of MDmc learned concurrently presented visual discrimination problems as quickly as unoperated control monkeys but showed impaired reinforcer devaluation effects. This finding suggests that the neural circuitry for control of behavioral choice by changes in reinforcer value includes MDmc.

  18. AAV8-mediated hepatic gene transfer in infant rhesus monkeys (Macaca mulatta).

    PubMed

    Wang, Lili; Bell, Peter; Lin, Jianping; Calcedo, Roberto; Tarantal, Alice F; Wilson, James M

    2011-11-01

    Many genetic metabolic diseases manifest in infancy, therefore, it is important to develop effective treatments that could be implemented at this time. Adeno-associated virus serotype 8 (AAV8) gene transfer has been studied in neonatal mouse, cat, and dog models and shown some efficacy with a single hepatic injection at birth. AAV8-mediated liver gene transfer has also generated sustained therapeutic effects in feline and canine models of lysosomal storage disorders. In these models, delaying the age of vector treatment increased gene transfer stability. The growth rate of infant nonhuman primates is more similar to the growth trajectory of humans, thus infant monkeys provide an excellent model to study AAV gene transfer efficiency, stability, and safety. In this study, we report for the first time that AAV8-mediated hepatic gene transfer in infant monkeys is safe and efficient but less stable when compared to adolescent animals. Infant monkeys administered AAV8 intravenously at 1 week postnatal age achieved up to 98% transduction of hepatocytes within 7 days of injection; however, there was significant dilution of genomes and loss of transgene expression 35 days postadministration. Delaying the injection to 1 month postnatal age did not improve stability of transduction but decreased the antibody response to AAV8 capsid.

  19. Effect of 50% distal small bowel resection on gastric emptying in Rhesus monkeys.

    PubMed Central

    Hall, A W; Moossa, A R; Skinner, D B

    1977-01-01

    The effect of bowel resection, sufficient to cause gastric secretory changes, on gastric emptying is unknown. Gastric evacuation was characterized in 8 Rhesus monkeys by a modification of George's double sampling test meal. Fifty per cent distal small bowel resection was then performed. Gastric emptying was again studied at 6 weeks and 6 months. The rate constant fell from -0.00289 +/- 0.000467 (+/-1 SEM) to -0.00232 +/- 0.00106 during the early phase, but role to -0.00308 +/- 0.00186 by 6 months, neither value being statistically different from the preoperative values. T1/2 rose from 125.2 +/- 19.2 mins to 367 +/- 173.4 mins by 6 weeks and to 380.9 +/- 161.6 mins by the end of the experiments. Corresponding values for T were: control period 425.8 +/- 63.2 mins, early phase 1223 +/- 589 mins and late phase 1245.9 +/- 529.6 mins. None of these changes were statistically significant. Alterations in emptying time within each animal were consistent at the two postoperative phases. Although the two animals showing acceleration of evacuation were those with least change in secretion, compensation for the observed increase in output of gastric juice did not materially alter the results. PMID:402124

  20. 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.

  1. Selection of genetic variants of simian immunodeficiency virus in persistently infected rhesus monkeys.

    PubMed Central

    Burns, D P; Desrosiers, R C

    1991-01-01

    Genetic and antigenic variation may be one means by which lentiviruses that cause AIDS avoid elimination by host immune responses. Genetic variation in the envelope gene (env) was studied by comparing the nucleotide sequences of 27 clones obtained from two rhesus monkeys infected with molecularly cloned simian immunodeficiency virus. All 27 clones differed from each other and differed from the input clone in the gp120 (SU) portion of the envelope gene. Nucleotide substitutions were shown to accumulate with time at an average rate of 8.5 per 1,000 per year in SU. Surprisingly, the majority of nucleotide substitutions (81%) resulted in amino acid changes. Variation in SU was not random but occurred predominantly in five discrete regions. Within these variable regions, a remarkable 98% of the nucleotide substitutions changed the amino acid. These results demonstrate that extensive sequence variability accumulates in vivo after infection with molecularly cloned virus and that selection occurs in vivo for changes in distinct variable regions in env. PMID:2002545

  2. Design and performance of a multichannel vestibular prosthesis that restores semicircular canal sensation in rhesus monkey

    PubMed Central

    Chiang, Bryce; Fridman, Gene Y.; Dai, Chenkai; Rahman, Mehdi A.; Della Santina, Charles C.

    2012-01-01

    In normal individuals, the vestibular labyrinths sense head movement and mediate reflexes that maintain stable gaze and posture. Bilateral loss of vestibular sensation causes chronic disequilibrium, oscillopsia, and postural instability. We describe a new multichannel vestibular prosthesis (MVP) intended to restore modulation of vestibular nerve activity with head rotation. The device comprises motion sensors to measure rotation and gravitoinertial acceleration, a microcontroller to calculate pulse timing, and stimulator units that deliver constant-current pulses to microelectrodes implanted in the labyrinth. This new MVP incorporates many improvements over previous prototypes, including a 50% decrease in implant size, a 50% decrease in power consumption, a new microelectrode array design meant to simplify implantation and reliably achieve selective nerve-electrode coupling, multiple current sources conferring ability to simultaneously stimulate on multiple electrodes, and circuitry for in vivo measurement of electrode impedances. We demonstrate the performance of this device through in vitro bench-top characterization and in vivo physiological experiments with a rhesus macaque monkey. PMID:21859631

  3. The proinflammatory cytokine network: interactions in the CNS and blood of rhesus monkeys.

    PubMed

    Reyes, T M; Coe, C L

    1998-01-01

    Proinflammatory cytokines [interleukin (IL)-1 and -6 and tumor necrosis factor-alpha] function within a complex network, stimulating the release of one another, as well as other cytokine agonists and antagonists. These interactions have not been as widely studied in vivo. Therefore, the following studies measured cytokines in blood and cerebrospinal fluid (CSF) from juvenile rhesus monkeys after intravenous administration of cytokines. IL-1 alpha and IL-1 beta were equally effective in elevating blood levels of IL-6. In contrast, IL-1 beta was the only cytokine that significantly elevated IL-6 levels in the CSF. Interestingly, both IL-1 and IL-6 increased levels of IL-1 receptor antagonist in the blood and comparably stimulated the release of cortisol. A second study confirmed that the IL-1-induced IL-6 in CSF was brain derived and not a result of diffusion from blood. This research extends studies of the cytokine cascade to the central nervous system (CNS), highlighting the brain response to peripheral activation.

  4. Processing of band-passed noise in the lateral auditory belt cortex of the rhesus monkey.

    PubMed

    Rauschecker, Josef P; Tian, Biao

    2004-06-01

    Neurons in the lateral belt areas of rhesus monkey auditory cortex were stimulated with band-passed noise (BPN) bursts of different bandwidths and center frequencies. Most neurons responded much more vigorously to these sounds than to tone bursts of a single frequency, and it thus became possible to elicit a clear response in 85% of lateral belt neurons. Tuning to center frequency and bandwidth of the BPN bursts was analyzed. Best center frequency varied along the rostrocaudal direction, with 2 reversals defining borders between areas. We confirmed the existence of 2 belt areas (AL and ML) that were laterally adjacent to the core areas (R and A1, respectively) and a third area (CL) adjacent to area CM on the supratemporal plane (STP). All 3 lateral belt areas were cochleotopically organized with their frequency gradients collinear to those of the adjacent STP areas. Although A1 neurons responded best to pure tones and their responses decreased with increasing bandwidth, 63% of the lateral belt neurons were tuned to bandwidths between 1/3 and 2 octaves and showed either one or multiple peaks. The results are compared with previous data from visual cortex and are discussed in the context of spectral integration, whereby the lateral belt forms a relatively early stage of processing in the cortical hierarchy, giving rise to parallel streams for the identification of auditory objects and their localization in space.

  5. 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.

  6. Effect of low zinc formula on zinc status, zinc absorption and immune function in rhesus monkeys

    SciTech Connect

    Loennerdal, B.; Polberger, S.; Vruwink, K.; Fletcher, M.; Gershwin, M.E. )

    1991-03-15

    Low Zn intake causes decreased growth and impaired immune function during infancy. However, little is known about the events causing these outcomes and the body's capacity to adapt to a low intake. To study this, 3 groups of infant rhesus monkeys were fed from birth to 5 mo of age either a regular infant formula or a low Zn formula. Since the Fe level of formula may affect Zn absorption, the low Zn formula was given without or with Fe supplement. At monthly intervals, Zn absorption was assessed by gavage feeding with {sup 65}Zn and whole body counting immediately after and at 4 to 7 days post-dosing. Before each dosing, blood samples were drawn and hemoglobin, ferritin, cytokines, plasma Zn and Cu, and metallothionein (Mt) were determined. Infants fed low Zn formula had slower weight gain than controls; however, plasma Zn levels were normal. Plasma Mt levels were lower in low Zn infants at 1 mo, but normalized thereafter. Zn retention was higher in both low Zn groups than in controls. Hemoglobin levels were normal in all groups and Fe intake did not affect Zn absorption or status. Neutrophil chemotaxis assessed at the end of the study was impaired in low Zn infants as compared to controls. In conclusion, low Zn intake causes up-regulation of Zn absorption but not enough to fully compensate for the lower Zn intake.

  7. Determination of genetic status in a closed colony of rhesus monkeys (Macaca mulatta).

    PubMed

    Andrade, Marcia C Ribeiro; Penedo, Maria Cecilia T; Ward, Thea; Silva, Virgilio F; Bertolini, Luciana R; Roberts, Jeffrey A; Leite, Jose Paulo G; Cabello, Pedro H

    2004-07-01

    The long-term management of breeding colonies requires some measure of genetic diversity in the animal population. For the maintenance of breeding colonies of monkeys used for biomedical research, known pedigrees supply precise data to determine the genetic status of colonies. We present data of genetic analyses in an old closed colony of rhesus macaques (Macaca mulatta) that was established in 1932 with 100 animals. For more than 40 years, the animals were kept on an isolated island and, in 1980, single-male breeding groups were established. A total of 333 DNA samples of these animals were typed to 20 microsatellite markers using multiplex PCR in order to verify inbreeding coefficient (alpha) and level of heterozygosity. We found an average heterozygosity of 64% and obtained alpha=-0.03293 (+/-0.00573). Our results indicate that the reproductive strategy used was effective because consanguineous breeding was avoided. A continuous genetic program must be carried out in order to obtain better quality primates for biomedical research.

  8. Contributions of the hippocampus and entorhinal cortex to rapid visuomotor learning in rhesus monkeys.

    PubMed

    Yang, Tianming; Bavley, Rachel L; Fomalont, Kevin; Blomstrom, Kevin J; Mitz, Andrew R; Turchi, Janita; Rudebeck, Peter H; Murray, Elisabeth A

    2014-09-01

    The hippocampus and adjacent structures in the medial temporal lobe are essential for establishing new associative memories. Despite this knowledge, it is not known whether the hippocampus proper is essential for establishing such memories, nor is it known whether adjacent regions like the entorhinal cortex might contribute. To test the contributions of these regions to the formation of new associative memories, we trained rhesus monkeys to rapidly acquire arbitrary visuomotor associations, i.e., associations between visual stimuli and spatially directed actions. We then assessed the effects of reversible inactivations of either the hippocampus (Experiment 1) or entorhinal cortex (Experiment 2) on the within-session rate of learning. For comparison, we also evaluated the effects of the inactivations on performance of problems of the same type that had been well learned prior to any inactivations. We found that inactivation of the entorhinal cortex but not hippocampus produced impairments in acquiring novel arbitrary associations. The impairment did not extend to the familiar, previously established associations. These data indicate that the entorhinal cortex is causally involved in establishing new associations, as opposed to retrieving previously learned associations. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

  9. 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.

  10. 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.

  11. Platelet monoamine oxidase activity predicts alcohol sensitivity and voluntary alcohol intake in rhesus monkeys.

    PubMed

    Wargelius, Hanna-Linn; Fahlke, Claudia; Suomi, Stephen J; Oreland, Lars; Higley, James Dee

    2010-02-01

    Platelet monoamine oxidase B (MAO-B) has been proposed to be a biological marker for the properties of monoamine systems, with low activity being associated with vulnerability for high scores on personality traits such as sensation seeking, monotony avoidance, and impulsiveness, as well as for vulnerability for alcoholism. In the present study, platelet MAO-B activity was analysed in 78 rhesus macaques, and its relation to voluntary alcohol intake and behaviours after intravenous alcohol administration was observed. Monkeys with low platelet MAO-B activity had low levels of 5-hydroxyindole acetic acid in cerebrospinal fluid and showed excessive aggression after alcohol administration. A novel finding was that animals with low platelet MAO-B activity showed less intoxication following alcohol administration. As we have shown previously, they also voluntarily consumed more alcohol. We here replicate results from studies on both humans and non-human primates, showing the utility of platelet MAO as a marker for risk behaviours and alcohol abuse. Furthermore, we link platelet MAO activity to alcohol sensitivity.

  12. Clinically employed opioid analgesics produce antinociception via μ-δ opioid receptor heteromers in Rhesus monkeys.

    PubMed

    Yekkirala, Ajay S; Banks, Matthew L; Lunzer, Mary M; Negus, Stevens S; Rice, Kenner C; Portoghese, Philip S

    2012-09-19

    Morphine and related drugs are widely employed as analgesics despite the side effects associated with their use. Although morphine is thought to mediate analgesia through mu opioid receptors, delta opioid receptors have been implicated in mediating some side effects such as tolerance and dependence. Here we present evidence in rhesus monkeys that morphine, fentanyl, and possibly methadone selectively activate mu-delta heteromers to produce antinociception that is potently antagonized by the delta opioid receptor antagonist, naltrindole (NTI). Studies with HEK293 cells expressing mu-delta heteromeric opioid receptors exhibit a similar antagonism profile of receptor activation in the presence of NTI. In mice, morphine was potently inhibited by naltrindole when administered intrathecally, but not intracerebroventricularly, suggesting the possible involvement of mu-delta heteromers in the spinal cord of rodents. Taken together, these results strongly suggest that, in primates, mu-delta heteromers are allosterically coupled and mediate the antinociceptive effects of three clinically employed opioid analgesics that have been traditionally viewed as mu-selective. Given the known involvement of delta receptors in morphine tolerance and dependence, our results implicate mu-delta heteromers in mediating both antinociception and these side effects in primates. These results open the door for further investigation in humans.

  13. Early experience affects the strength of vigilance for threat in rhesus monkey infants

    PubMed Central

    Mandalaywala, Tara M.; Parker, Karen J.; Maestripieri, Dario

    2014-01-01

    Both human and nonhuman primates exhibit a cognitive bias to social threat, but little is known about how this bias develops. We investigated the development of threat bias in free-ranging infant rhesus macaques (Macaca mulatta) at 3 (N = 45) and 9 (N = 46) months of age. Three-month-old infant monkeys did not display bias, but 9-month-olds exhibited increased maintenance of attention to threatening social stimuli (vigilance for threat). To examine whether the social environment affected vigilance for threat, behavioral data on maternal rank and protectiveness were collected across the first 12 weeks of life for infants tested at 9 months. Nine-month-old infants of high-ranking mothers and more protective mothers displayed greater vigilance for threat than infants of lower-ranking and less protective mothers. These results demonstrate that infant social cognition is malleable and shaped by mothers both directly (protectiveness) and indirectly (rank), as maternal characteristics affect infants’ social experiences. PMID:25125426

  14. Age-related changes in glial cells of dopamine midbrain subregions in rhesus monkeys.

    PubMed

    Kanaan, Nicholas M; Kordower, Jeffrey H; Collier, Timothy J

    2010-06-01

    Aging remains the strongest risk factor for developing Parkinson's disease (PD), and there is selective vulnerability in midbrain dopamine (DA) neuron degeneration in PD. By tracking normal aging-related changes with an emphasis on regional specificity, factors involved in selective vulnerability and resistance to degeneration can be studied. Towards this end, we sought to determine whether age-related changes in microglia and astrocytes in rhesus monkeys are region-specific, suggestive of involvement in regional differences in vulnerability to degeneration that may be relevant to PD pathogenesis. Gliosis in midbrain DA subregions was measured by estimating glia number using unbiased stereology, assessing fluorescence intensity for proteins upregulated during activation, and rating morphology. With normal aging, microglia exhibited increased staining intensity and a shift to more activated morphologies preferentially in the vulnerable substantia nigra-ventral tier (vtSN). Astrocytes did not exhibit age-related changes consistent with an involvement in regional vulnerability in any measure. Our results suggest advancing age is associated with chronic mild inflammation in the vtSN, which may render these DA neurons more vulnerable to degeneration.

  15. 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.

  16. Maternal and Fetal Pharmacokinetics of Oral Radiolabeled and Authentic Bisphenol A in the Rhesus Monkey

    PubMed Central

    VandeVoort, Catherine A.; Gerona, Roy R.; vom Saal, Frederick S.; Tarantal, Alice F.; Hunt, Patricia A.; Hillenweck, Anne; Zalko, Daniel

    2016-01-01

    The present study was conducted in pregnant rhesus monkeys to determine the rapidity and extent to which BPA reaches the fetal compartment following oral ingestion, and the 24-hr fate of BPA. To assess metabolism changes during the course of pregnancy, we compared BPA biotransformation during the second and third trimesters in the same animals, measuring the levels of sulfated, gluronidated, and free BPA in maternal serum, amniotic fluid, and fetal serum. All animals showed measurable unconjugated and conjugated BPA in the fetal compartment and slow clearance compared to maternal serum. There were higher levels of BPA-G in amniotic fluid at 150 days gestation compared to 100 days gestation, as well as higher levels of BPA-G than BPA-S. We also monitored 3H-BPA (and metabolites) in key tissues and excreta from a mother and fetus and from a non-pregnant female. The elimination of radioactivity was rapid, but residues were still detectable 24 hr after dosing in all tissues analyzed. These data suggest that, in primates, rapid maternal processing of BPA does not alleviate the risk of exposure to the developing fetus. This study elevates concerns about levels of current BPA human exposure from potentially a large number of unknown sources and the risks posed to developing fetuses. PMID:27930651

  17. 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.

  18. 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.

  19. Rhesus monkeys correctly read the goal-relevant gestures of a human agent.

    PubMed

    Hauser, Marc D; Glynn, David; Wood, Justin

    2007-08-07

    When humans point, they reveal to others their underlying intent to communicate about some distant goal. A controversy has recently emerged based on a broad set of comparative and phylogenetically relevant data. In particular, whereas chimpanzees (Pan troglodytes) have difficulty in using human-generated communicative gestures and actions such as pointing and placing symbolic markers to find hidden rewards, domesticated dogs (Canis familiaris) and silver foxes (Urocyon cinereoargenteus) readily use such gestures and markers. These comparative data have led to the hypothesis that the capacity to infer communicative intent in dogs and foxes has evolved as a result of human domestication. Though this hypothesis has met with challenges, due in part to studies of non-domesticated, non-primate animals, there remains the fundamental question of why our closest living relatives, the chimpanzees, together with other non-human primates, generally fail to make inferences about a target goal of an agent's communicative intent. Here, we add an important wrinkle to this phylogenetic pattern by showing that free-ranging rhesus monkeys (Macaca mulatta) draw correct inferences about the goals of a human agent, using a suite of communicative gestures to locate previously concealed food. Though domestication and human enculturation may play a significant role in tuning up the capacity to infer intentions from communicative gestures, these factors are not necessary.

  20. Discriminative stimulus, reinforcing, physical dependence, and antinociceptive effects of oxycodone in mice, rats, and rhesus monkeys.

    PubMed

    Beardsley, Patrick M; Aceto, Mario D; Cook, Charles D; Bowman, Edward R; Newman, Jennifer L; Harris, Louis S

    2004-08-01

    Despite oxycodone's (4,5-epoxy-14-hydroxy-3-methoxy-17-methylmorphinan-6-one) history of clinical use and the attention it has received as a drug of abuse, few reports have documented its pharmacology's relevance to its abuse or its mechanism of action. The purposes of the present study were to further characterize the analgesic effects of oxycodone, its mechanism of action, and its effects in terms of its relevance to its abuse liability. The results indicate that oxycodone had potent antinociceptive effects in the mouse paraphenylquinone writhing, hot-plate, and tail-flick assays, in which it appeared to be acting as a mu-opioid receptor agonist. It generalized to the heroin discriminative stimulus and served as a positive reinforcer in rats and completely suppressed withdrawal signs in morphine-dependent rhesus monkeys. These results suggest that the analgesic and abuse liability effects of oxycodone are likely mediated through mu-opioid receptors and provide the first laboratory report of its discriminative stimulus, reinforcing, and morphine cross-dependency effects.

  1. 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

  2. Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses.

    PubMed

    Santra, Sampa; Barouch, Dan H; Korioth-Schmitz, Birgit; Lord, Carol I; Krivulka, Georgia R; Yu, Faye; Beddall, Margaret H; Gorgone, Darci A; Lifton, Michelle A; Miura, Ayako; Philippon, Valerie; Manson, Kelledy; Markham, Phillip D; Parrish, John; Kuroda, Marcelo J; Schmitz, Jörn E; Gelman, Rebecca S; Shiver, John W; Montefiori, David C; Panicali, Dennis; Letvin, Norman L

    2004-07-27

    Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T lymphocyte response remain unclear. We explored this issue in the simian human immunodeficiency virus/rhesus monkey model in the course of assessing the relative immunogenicity of vaccine regimens that included a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. Recombinant vaccinia virus, recombinant modified vaccinia Ankara (MVA), and recombinant fowlpox were comparable in their immunogenicity. Moreover, whereas the magnitude of the peak vaccine-elicited T lymphocyte responses in the recombinant pox virus-boosted monkeys was substantially greater than that seen in the monkeys immunized with plasmid DNA alone, the magnitudes of recombinant pox boosted CTL responses decayed rapidly and were comparable to those of the DNA-alone-vaccinated monkeys by the time of viral challenge. Consistent with these comparable memory T cell responses, the clinical protection seen in all groups of experimentally vaccinated monkeys was similar. This study, therefore, indicates that the steady-state memory, rather than the peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine.

  3. Use of enclosures with functional vertical space by captive rhesus monkeys (Macaca mulatta) involved in biomedical research.

    PubMed

    Clarence, Wendy M; Scott, Jennifer P; Dorris, Michael C; Paré, Martin

    2006-09-01

    We assessed space use by 2 pairs of captive female rhesus monkeys recently transferred into 2 enclosures moderately larger than their former traditional research cages and providing elevated perches at or above human eye level for all monkeys. This new space did not affect the ongoing biomedical research in which these captive monkeys were involved, and we sought to determine whether they used the elevated positions preferentially, as do wild animals. The frequency and duration of visits at each of the 9 distinct regions within these enclosures was calculated during 30-min morning and evening sessions over 20 d. We found that the monkeys frequented all regions of their enclosures in a similar manner during both morning and evening sessions. However, the duration spent at each region varied significantly between morning and evening sessions, with high perches being chosen preferentially in the evenings. Overall, the monkeys spent the majority of their time at elevated positions. These results support the view that access to functional vertical space provides a preferred environment for species- specific behavior and is an option that should be considered by other research facilities.

  4. MODERATE PRENATAL ALCOHOL EXPOSURE AND SEROTONIN GENOTYPE INTERACT TO ALTER CNS SEROTONIN FUNCTION IN RHESUS MONKEYS OFFSPRING

    PubMed Central

    Schneider, Mary L.; Moore, Colleen F.; Barr, Christina S.; Larson, Julie A.; Kraemer, Gary W.

    2010-01-01

    Background Moderate prenatal alcohol exposure can contribute to neurodevelopmental impairments and disrupt several neurotransmitter systems. We examined the timing of moderate level alcohol exposure, serotonin transporter gene polymorphic region variation (rh5-HTTLPR), and levels of primary serotonin and dopamine metabolites in cerebrospinal fluid (CSF) in rhesus monkeys. Methods Thirty-two 30-month old rhesus monkeys (Macaca mulatta) from four groups of females were assessed: (1) early alcohol-exposed group (n = 9), in which mothers voluntarily consumed 0.6 g/kg/day alcohol solution on gestational days 0 – 50; (2) middle-to-late gestation alcohol-exposed group (n = 6), mothers consumed 0.6 g/kg/day alcohol solution on gestational days 50 – 135; (3) a continuous-exposure group (n = 8), mothers consumed 0.6 g/kg/day alcohol solution on gestational days 0 – 135; and (4) controls (n = 9), mothers consumed an isocaloric control solution on gestational days 0 – 50, 50 – 135, or 0 – 135. Serotonin transporter promoter region allelic variants (homozygous s/s or heterozygous s/l versus homozygous l/l) were determined. We examined CSF concentrations of the 5-HT and DA metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA), respectively, at baseline and 50 hours after separation from cage-mates, when the monkeys were 30 months old. Results Early- and middle-to-late gestation-alcohol exposed monkeys carrying the short allele had lower concentrations of 5-HIAA in CSF relative to other groups. Concentrations of 5-HIAA in CSF were lower for s allele carriers and increased from baseline relative to pre-separation values, while 5-HIAA levels in l/l allele carriers were not affected by separation. Monkeys carrying the short allele had lower basal concentrations of HVA in CSF compared to monkeys homozygous for the long allele. Conclusion Carrying the s allele of the 5-HT transporter increased the probability of reduced 5-HIAA in early- and middle

  5. 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.

  6. In vivo assessment of mitochondrial toxicity of metacavir in Rhesus monkeys after three months of intravenous administration

    PubMed Central

    Zeng, Wen; Cheng, An-chun; Chen, Zheng-li; Luo, Qi-hui; Sun, Yu-bo; Li, Zhan; Bi, Feng-jun

    2009-01-01

    Aim: To explore the potential mitochondrial toxicities and their severities of intravenously administered metacavir, a nucleoside analog, in rhesus monkeys. Methods: Totally 21 rhesus monkeys were randomly divided into 4 groups: metacavir 120 mg/kg group, metacavir 40 mg/kg group, zidovudine(AZT) 50 mg/kg group, and blank control group. Animals were killed after the completion of dosing or further observed in a 4-week recovery phase. Changes of structure of mitochondria in liver, kidney, skeletal muscles, and cardiac muscles were observed under transmission electron microscope(TEM). Changes of the activities of mitochondrial respiratory chain complexes and mitochondrial DNA were also determined. Results: In metacavir 120 mg/kg group, some mitochondrial injuries were found in skeletal muscle, cardiac muscle, and liver, including that some cristae was broken and became sparse in density in the skeletal muscle, the morphology and size of mitochondria remained unchanged. Metacavir decreased the activities of respiratory chain complexes I and II and the mtDNA contents in three tissues in a dose-dependent manner; however, the extent of such decrease was lower than that in AZT 50 mg/kg group. The mitochondrial injuries in metacavir 40 mg/kg group were mild in each tissue and no obvious change in mitochondrial function was noted. On week 4 in the recovery phase, results showed that all these injuries were reversible after drug withdrawal. Conclusion: These results suggest that metacavir has not a high risk for potential mitochondrial-related effects in rhesus monkeys. PMID:19915582

  7. 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

  8. 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

  9. Common features of mucosal and peripheral antibody responses elicited by candidate HIV-1 vaccines in rhesus monkeys.

    PubMed

    Li, Hualin; Stephenson, Kathryn E; Kang, Zi Han; Lavine, Christy L; Seaman, Michael S; Barouch, Dan H

    2014-11-01

    Human immunodeficiency virus type 1 (HIV-1) vaccines that elicit protective antibody responses at mucosal sites would be highly desirable. Here, we report that intramuscular immunization of candidate HIV-1 vaccine vectors and purified Env proteins elicited potent and durable humoral immune responses in colorectal mucosa in rhesus monkeys. The kinetics, isotypes, functionality, and epitope specificity of these mucosal antibody responses were similar to those of peripheral responses in serum. These data suggest a close immunological relationship between mucosal and systemic antibody responses following vaccination in primates.

  10. 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.

  11. Dose-dependent effects of siRNA-mediated inhibition of SCAP on PCSK9, LDLR, and plasma lipids in mouse and rhesus monkey[S

    PubMed Central

    Jensen, Kristian K.; Tadin-Strapps, Marija; Wang, Sheng-ping; Hubert, James; Kan, Yanqing; Ma, Yong; McLaren, David G.; Previs, Stephen F.; Herath, Kithsiri B.; Mahsut, Ablatt; Liaw, Andy; Wang, Shubing; Stout, Steven J.; Keohan, CarolAnn; Forrest, Gail; Coelho, David; Yendluri, Satya; Williams, Stephanie; Koser, Martin; Bartz, Steven; Akinsanya, Karen O.; Pinto, Shirly

    2016-01-01

    SREBP cleavage-activating protein (SCAP) is a key protein in the regulation of lipid metabolism and a potential target for treatment of dyslipidemia. SCAP is required for activation of the transcription factors SREBP-1 and -2. SREBPs regulate the expression of genes involved in fatty acid and cholesterol biosynthesis, and LDL-C clearance through the regulation of LDL receptor (LDLR) and PCSK9 expression. To further test the potential of SCAP as a novel target for treatment of dyslipidemia, we used siRNAs to inhibit hepatic SCAP expression and assess the effect on PCSK9, LDLR, and lipids in mice and rhesus monkeys. In mice, robust liver Scap mRNA knockdown (KD) was achieved, accompanied by dose-dependent reduction in SREBP-regulated gene expression, de novo lipogenesis, and plasma PCSK9 and lipids. In rhesus monkeys, over 90% SCAP mRNA KD was achieved resulting in approximately 75, 50, and 50% reduction of plasma PCSK9, TG, and LDL-C, respectively. Inhibition of SCAP function was demonstrated by reduced expression of SREBP-regulated genes and de novo lipogenesis. In conclusion, siRNA-mediated inhibition of SCAP resulted in a significant reduction in circulating PCSK9 and LDL-C in rodent and primate models supporting SCAP as a novel target for the treatment of dyslipidemia. PMID:27707816

  12. Differential Effects of Sodium Butyrate and Lithium Chloride on Rhesus Monkey Trophoblast Differentiation

    PubMed Central

    Kumar, Priyadarsini; Thirkill, Twanda L.; Ji, Jennifer; Monte, Louise H.; Douglas, Gordon C.

    2015-01-01

    Trophoblast differentiation during early placental development is critical for successful pregnancy and aberrant differentiation causes preeclampsia and early pregnancy loss. During the first trimester, cytotrophoblasts are exposed to low oxygen tension (equivalent to~2%-3% O2) and differentiation proceeds along an extravillous pathway (giving rise to invasive extravillous cytotrophoblasts) and a villous pathway (giving rise to multinucleated syncytiotrophoblast). Interstitial extravillous cytotrophoblasts invade the decidua, while endovascular extravillous cytotrophoblasts are involved in re-modelling uterine spiral arteries. We tested the idea that sodium butyrate (an epigenetic modulator) induces trophoblast differentiation in early gestation rhesus monkey trophoblasts through activation of the Wnt/β-catenin pathway. The results show that syncytiotrophoblast formation was increased by butyrate, accompanied by nuclear accumulation of β-catenin, and increased expression of EnvV2 and galectin-1 (two factors thought to be involved in trophoblast fusion). Surprisingly, the expression of GCM1 and syncytin-2 was not affected by sodium butyrate. When trophoblasts were incubated with lithium chloride, a GSK3 inhibitor that mimics Wnt activation, nuclear accumulation of β-catenin also occurred but differentiation into syncytiotrophoblast was not observed. Instead the cells differentiated to mononucleated spindle-shaped cells and showed molecular and behavioral characteristics of endovascular trophoblasts. Another highly specific inhibitor of GSK3, CHIR99021, failed to induce endovascular trophoblast characteristics. These observations suggest that activation of the Wnt/β-catenin pathway correlates with both trophoblast differentiation pathways, but that additional factors determine specific cell fate decisions. Other experiments suggested that the differential effects of sodium butyrate and lithium chloride might be explained by their effects on TNFα production. The

  13. 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

  14. Actigraphy-based sleep parameters during the reinstatement of methamphetamine self-administration in rhesus monkeys.

    PubMed

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

    2016-04-01

    The objective of this study was to investigate nighttime activity of nonhuman primates during extinction and cue- and drug-primed reinstatement of methamphetamine self-administration. Adult rhesus monkeys (Macaca mulatta; n = 5) self-administered methamphetamine (0.01 mg/kg/injection, i.v.) under a fixed-ratio 20 schedule of reinforcement. Saline infusions were then substituted for methamphetamine and stimulus light (drug-conditioned stimulus presented during drug self-administration) withheld until subjects reached extinction criteria. Drug- and cue-induced reinstatement effects were evaluated after i.v. noncontingent priming injections of methamphetamine (0.03, 0.1, or 0.3 mg/kg). Activity-based sleep measures were evaluated with Actiwatch monitors a week before (baseline nighttime activity parameters) and throughout the protocol. Although methamphetamine self-administration did not significantly affect nighttime activity compared to baseline, sleeplike parameters were improved during extinction compared to self-administration maintenance. Priming injection of 0.1 mg/kg methamphetamine, but not 0.03 or 0.3 mg/kg, induced significant reinstatement effects. These behavioral responses were accompanied by nighttime outcomes, with increased sleep fragmentation and decreased sleep efficiency in the night following 0.1 mg/kg methamphetamine-induced reinstatement. In the absence of both drug and drug-paired cues (extinction conditions), nighttime activity decreased compared to self-administration maintenance. Additionally, effective reinstatement conditions impaired sleeplike measures. Our data indicate that the reintroduction of the stimulus light as a drug-paired cue increased nighttime activity.

  15. Body weight decreases induced by estradiol in female rhesus monkeys are dependent upon social status.

    PubMed

    Michopoulos, Vasiliki; Wilson, Mark E

    2011-03-01

    Gonadal steroids regulate appetite and thus body weight. In addition, continuous exposure to stressors negatively influences appetite through circuits likely distinct from those of gonadal steroids. The occurrence of adverse metabolic consequences due to chronic exposure to psychosocial stressors is twice as frequent in women as men, implicating a role for ovarian hormones, estradiol (E2) and progesterone (P4), in modulating stress-induced changes in appetite. Using social subordination in female macaques as a model of social stress, the current study tested the hypothesis that subordinate females would lose more weight during E2 treatment and gain less weight during P4 administration than dominant females. Because polymorphisms in the gene encoding the serotonin transporter (5HTT; SCL6A4) are known to alter responsivity to stress, we hypothesized that weight loss during E2 administration would be greatest in females with the short variant (s-variant) allele of 5HTT. Dominant females were significantly heavier than subordinate animals throughout the study, a result consistent with previous accounts of food intake when animals are fed a low-fat, high-fiber diet. Females with the s-variant 5HTT genotype weighed significantly less than l/l animals. Dominant animals lost significantly more weight than subordinate animals during E2 treatment. Administration of P4 blocked the weight-reducing effects of E2 in all females, regardless of social status. These data provide evidence that social subordination modulates the influence of ovarian steroid hormones on body weight in female rhesus monkeys independent of 5HTT genotype. Given the prosocial effects of these steroids, future studies are necessary to determine whether status differences in E2-induced weight loss are due to diminished food intake and or increases in energy expenditure and how the change in energy availability during E2 treatments relates to a female's motivation to interact with conspecifics.

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

    PubMed

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

    2012-11-01

    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.

  17. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys

    PubMed Central

    Maguire, David R.; France, Charles P.

    2015-01-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Poly-drug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated co-administration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ9-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32–32 μg/kg/infusion, i.v.) generated an inverted U-shaped dose–effect curve. Administered acutely, Δ9-THC (0.01–0.32 mg/kg, s.c.) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ9-THC (0.01–0.1 mg/kg/12hr, s.c.) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ9-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist. PMID:26397756

  18. Effects of buspirone and gepirone on i.v. cocaine self-administration in rhesus monkeys.

    PubMed

    Gold, L H; Balster, R L

    1992-01-01

    Buspirone and gepirone were evaluated as potential pharmacotherapies for cocaine abuse by studying the effects of acute and repeated treatment on IV cocaine self-administration in rhesus monkeys. Chlorpromazine was also evaluated as a positive control. Effects of IV drug pretreatments were tested during daily 60-min sessions with lever-pressing reinforced under a fixed-ratio 10 schedule of 0.02 or 0.05 mg/kg cocaine infusions. Acute pretreatment with buspirone (0.1 and 0.3 mg/kg, IV) increased rates of cocaine self-administration without disrupting food pellet consumption. Some doses of buspirone also produced changes in rates of cocaine self-administration without altering the within-session pattern of responding. In contrast, acute doses of gepirone had little effect on rates of cocaine self-administration, while disruptions in food consumption and changes in the within-session pattern of cocaine self-administration were obtained at the highest dose of gepirone tested (1.0 mg/kg). When either buspirone (0.1 and 0.3 mg/kg, IV) or gepirone (0.1 mg/kg, IV) were administered daily for 10 days, consistent effects on cocaine self-administration were not observed. Thus, the effects of acute buspirone administration on cocaine-maintained behavior were similar to the effects produced by chlorpromazine and other dopaminergic antagonists, whereas, gepirone was ineffective. These results provide some support for further evaluation of buspirone as a potential pharmacotherapy for cocaine abuse, although its lack of efficacy with repeated treatment is not encouraging. The negative results with gepirone provide less rationale for continued investigations with this drug, possibly because of its lesser involvement than buspirone with dopaminergic neurotransmission.

  19. 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.

  20. 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

  1. 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

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

    PubMed

    Rodriguez, Jesse S; McMahon, Lance R

    2014-10-05

    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.

  3. 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.

  4. Discriminative stimulus effects of intravenous heroin and its metabolites in rhesus monkeys: opioid and dopaminergic mechanisms.

    PubMed

    Platt, D M; Rowlett, J K; Spealman, R D

    2001-11-01

    Heroin has characteristic subjective effects that contribute importantly to its widespread abuse. Drug discrimination procedures in animals have proven to be useful models for investigating pharmacological mechanisms underlying the subjective effects of drugs in humans. However, surprisingly little information exists concerning the mechanisms underlying the discriminative stimulus (DS) effects of heroin. This study characterized the DS effects of heroin in rhesus monkeys trained to discriminate i.v. heroin from saline. In drug substitution experiments, heroin, its metabolites 6-monoacetylmorphine, morphine, morphine-6-glucuronide, and morphine-3-glucuronide, and the mu-agonists fentanyl and methadone engendered dose-dependent increases in heroin-lever responding, reaching average maximums of >80% (full substitution) at doses that did not appreciably suppress response rate. In contrast, the delta-agonist SNC 80, the kappa-agonist spiradoline, and the dopamine uptake blockers/releasers cocaine, methamphetamine, and GBR 12909 did not engender heroin-like DS effects regardless of dose. In antagonism studies, in vivo apparent pA2 and pK(B) values for naltrexone combined with heroin, morphine, and 6-monoacetylmorphine (8.0-8.7) were comparable with those reported previously for naltrexone antagonism of prototypical mu-agonists. The results show that the DS effects of heroin are pharmacologically specific and mediated primarily at mu-opioid receptors. Moreover, the acetylated and glucuronated metabolites of heroin appear to play significant roles in these effects. Despite previous speculation that morphine-3-glucuronide lacks significant opioid activity, it substituted fully for heroin in our study, suggesting that it can exhibit prominent mu-agonist effects in vivo.

  5. 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

  6. 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.

  7. Effects of daily delta-9-tetrahydrocannabinol treatment on heroin self-administration in rhesus monkeys.

    PubMed

    Maguire, David R; France, Charles P

    2016-04-01

    Opioid abuse remains a significant public health problem; together with the greater availability of marijuana in some regions there is an increasing likelihood that opioids and marijuana will be used together. Polydrug abuse is associated with increased toxicity and poorer treatment outcome; thus, a better understanding of the consequences of repeated coadministration of these drugs will facilitate the development of better prevention and treatment strategies. This study examined the effects of daily treatment with the cannabinoid receptor agonist delta-9-tetrahydrocannabinol (Δ-THC) and its discontinuation on self-administration of heroin in rhesus monkeys (n=4) lever-pressing under a fixed-ratio 30 schedule. Heroin self-administration (0.32-32 μg/kg/infusion, intravenously) generated an inverted U-shaped dose-effect curve. Administered acutely, Δ-THC (0.01-0.32 mg/kg, subcutaneously) dose dependently decreased responding for heroin and flattened the self-administration dose-effect curve. Daily treatment with Δ-THC (0.01-0.1 mg/kg/12 h, subcutaneously) either had no effect on or decreased responding for heroin. In addition, daily treatment did not significantly impact extinction of heroin self-administration or resumption of responding for heroin after extinction. Discontinuation of daily Δ-THC treatment did not systematically impact rates of heroin self-administration. These data suggest that repeated administration of a cannabinoid receptor agonist likely does not increase, and possibly decreases, the positive reinforcing effects of a mu opioid receptor agonist.

  8. Effects of l-methamphetamine treatment on cocaine- and food-maintained behavior in rhesus monkeys

    PubMed Central

    Kohut, Stephen J.; Bergman, Jack; Blough, Bruce E.

    2015-01-01

    Rationale Monoamine releasers with prominent dopaminergic actions, e.g., d-methamphetamine (d-MA), significantly reduce cocaine use and craving in clinical and preclinical laboratory studies. However, d-MA and related drugs also display high abuse potential, which limits their acceptability as agonist replacement medications for the management of Cocaine Use Disorder. Objectives The l-isomer of methamphetamine (l-MA), unlike d-MA, has preferential noradrenergic actions and is used medicinally with low, if any, abuse liability. The present study was conducted to determine whether l-MA could serve as an agonist replacement medication by both mimicking interoceptive effects of cocaine and decreasing intravenous (IV) cocaine self-administration. Methods Separate groups (N=4-5) of rhesus monkeys were studied to determine whether l-MA could (1) substitute for cocaine in subjects that discriminated intramuscular (IM) cocaine (0.4 mg/kg) from saline and, (2) decrease IV cocaine self-administration under a second-order FR2(VR16:S) schedule of reinforcement. Results l-MA, like d-MA but with approximately 5-fold lesser potency, substituted for cocaine in drug discrimination experiments in a dose-dependent manner. In IV self-administration studies, 5-10 day treatments with continuously infused l-MA (0.032-0.32 mg/kg/hr, IV) dose-dependently decreased cocaine-maintained responding; the highest dosage reduced cocaine intake to levels of saline self-administration without appreciable effects on food-maintained responding. Conclusions These results indicate that l-MA both shares discriminative-stimulus effects with cocaine and reduces cocaine self-administration in a behaviorally selective manner. l-MA and other compounds with a similar pharmacological profile deserve further evaluation for the management of Cocaine Use Disorder. PMID:26713332

  9. 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.

  10. Mortality in Captive Rhesus Monkeys (Macaca mulatta) in China Due to Infection with Yersinia pseudotuberculosis Serotype O:1a.

    PubMed

    Zhao, Na; Li, Meng; Amer, Said; Liu, Shelan; Luo, Jing; Wang, Shan; He, Hongxuan

    2016-09-01

    The most common serotypes of Yersinia pseudotuberculosis infecting non-human primates are serotypes O:1b, O:3, O:4, and O:7. The O:1a serotype has never been reported in non-human primates. The present study describes an outbreak of serotype O:1a with high fatality (6/18) in captive rhesus monkeys in China. Bacteria were isolated from different organs of the carcasses using standard microbiological procedures. The strain was identified using conventional and molecular techniques such as morphological and biochemical identification, serotype determination, PCR-sequence analysis based on the 16S rRNA gene, detection of virulence genes, and antimicrobial susceptibility testing. The pathogenicity was determined after experimental infection in mice. Taken together, the obtained data indicate that Y. pseudotuberculosis O:1a is a pathogen of concern and represents a potential threat to monkey conservation efforts.

  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. 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.

  13. 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.

  14. Normative Values of Retinal Oxygen Saturation in Rhesus Monkeys: The Beijing Intracranial and Intraocular Pressure (iCOP) Study

    PubMed Central

    Li, Jing; Yang, Yiquan; Yang, Diya; Liu, Xiangxiang; Sun, Yunxiao; Wei, Shifei; Wang, Ningli

    2016-01-01

    Objective To study the normal values of the retinal oxygen saturation in Rhesus monkeys and to evaluated repeatability and reproducibility of retinal oxygen saturation measurements. Methods Eighteen adult Rhesus macaque monkeys were included in this experimental study. An Oxymap T1 retinal oximeter (Oxymap, Reykjavik, Iceland) was used to perform oximetry on all subjects. Global arterial (SaO2) and venous oxygen saturation (SvO2), arteriovenous difference in SO2 were measured. In the first examination, each eye was imaged three times. At the following two examinations, each eye was imaged once. All examinations were finished in one month. P values were calculated to evaluate the difference between the measurements during three visits by performing an ANOVA. Intra-visit and inter-visit intraclass correlation coefficient (ICC) was determined. Results At baseline, the average SaO2 and SvO2 were 89.48 ± 2.64% and 54.85 ± 2.18%, respectively. The global A-V difference was 34.63 ± 1.91%. The difference between the three visits was not significant (p>0.05). The highest A-V difference in SO2 and lowest saturations were found in the inferotemporal quadrant. Intra-session and inter-visit repeatability were both high. For all oxygen saturation parameters, the ICC values of the intra-session repeatability ranged between 0.92 and 0.96. As found previously, a relatively high ICC value for inter-visit repeatability also was found for all oxygen saturation measurements, ranging between 0.86 and 0.94, with the lowest values in the infero-nasal quadrant. Conclusions Our study is the first to describe retinal SO2 in healthy Rhesus monkeys. In normal monkey eyes, the reproducibility and repeatability of retinal oximetry oxygen saturation measurements were high in the retinal arterioles and venules. Our results support that Oxymap T1 retinal oximetry is a suitable and reliable technique in monkey studies. PMID:26930659

  15. Effects of maternal marginal zinc deficiency on myelin protein profiles in the suckling rat and infant rhesus monkey.

    PubMed

    Liu, H; Oteiza, P I; Gershwin, M E; Golub, M S; Keen, C L

    1992-07-01

    In the current study, the effects of marginal Zn deficiency on myelin protein profiles in neonatal rats and rhesus monkeys were investigated. Following mating, rats were fed a Zn-adequate diet, ad libitum (50 micrograms Zn/g; 50 Zn AL), or a marginal Zn diet (10 micrograms Zn/g) from day 0 (10 Zn d0) or day 14 (10 Zn d14) of gestation to day 20 postnatal. An additional group of dams was restricted-fed the control diet to the food intake of the 10 Zn d0 group (50 Zn RF). Day 20 pup plasma and liver Zn concentrations in the 10 Zn groups were lower than in the 50 Zn groups. In a parallel experiment, rhesus monkeys were fed a Zn-adequate ad libitum diet (100 micrograms Zn/g) or a marginal Zn diet (4 micrograms Zn/g diet; MZD) throughout gestation and lactation. Day 30 monkey infant plasma and liver Zn levels were similar in the MZD and control groups. Rat brain and monkey brain cortex weights were similar among the dietary groups. The amount of myelin recovered (mg protein/g brain) from day 20 rat pups from the 10 Zn groups was lower than that recovered from the 50 Zn rat pups. Myelin recovery from the MZD and control monkey infants was similar. When myelin protein profiles were characterized, it was found that the percentages of high-molecular-weight (HMW) proteins and Wolfgram protein were higher, whereas the percentages of small and large basic proteins were lower in myelin from the 10 Zn d0 and 50 Zn RF pups compared to the distribution in the 50 Zn AL rat pups. Results for the 10 Zn d0 and 10 Zn d14 pups were similar for all of the parameters studied. The percentage of HMW proteins was higher and that of basic protein lower in myelin from MZD monkey infants compared to the percentage of these proteins in myelin from controls. Although the interpretation of the rat data is complicated because of the anorexia associated with Zn deficiency, the observed changes in monkey myelin protein profiles provide strong evidence that maternal Zn deficiency affects myelination

  16. 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

  17. The relationship between cocaine self-administration and actigraphy-based measures of sleep in adult rhesus monkeys

    PubMed Central

    Brutcher, Robert E.; Nader, Michael A.

    2013-01-01

    Rationale Clinical trials show that chronic cocaine users suffer from sleep disturbances and preclinical research has shown that acute sleep deprivation increases the rate of cocaine self-administration in rats. Objective This study examined the effect of cocaine self-administration on behavioral indices of sleep, and alternatively the effect of sleep disruption on cocaine-maintained responding by rhesus monkeys. Methods Seven adult rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a concurrent choice paradigm with food (three 1.0-g pellets) and cocaine (0.003–0.3 mg/kg) or saline presentation. For each monkey the lowest preferred dose of cocaine (> 80% cocaine choice) was determined. Activity data were analyzed during lights out (2000-0600) to determine sleep efficiency, sleep latency and total activity counts. Subsequently, the monkeys were sleep disrupted (awaken every hour during lights-out period) the night prior to food-cocaine choice sessions. Results Self-administration of the preferred dose of cocaine resulted in a significant decrease in sleep efficiency, with a significant increase in total lights-out activity. Sleep disruption significantly altered behavioral indices of sleep, similar to those seen following cocaine self-administration. However, sleep disruption did not affect cocaine self-administration under concurrent choice conditions. Conclusions Based on these findings, cocaine self-administration does appear to disrupt behavioral indices of sleep, although it remains to be determined if treatments that improve sleep measures can affect future cocaine taking. PMID:23604390

  18. 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

  19. Age-dependent decrease in the affinity of muscarinic M1 receptors in neocortex of rhesus monkeys.

    PubMed Central

    Vannucchi, M G; Goldman-Rakic, P S

    1991-01-01

    In vitro autoradiography on tissue sections and receptor assay in cortical membrane homogenates revealed that pirenzepine high-affinity muscarinic sites (M1) decrease in affinity in the prefrontal cortex and in other cortical areas of aged rhesus monkey (Macaca mulatta). Carbachol competition experiments detected only a single, low-affinity class of sites in old monkeys, while two classes of sites (low and high affinity) were observed in young adults. The change in affinity in the aged monkeys is not accompanied by a decrease in the density of these sites and, further, the age-related decline in the affinity of the M1 site is reversible. In the presence of Mg2+, the M1 muscarinic receptors in the aged monkeys were capable of forming carbachol high-affinity sites. These results provide evidence for age-dependent functional changes in receptor activity in cerebral cortex and indicate that these receptors maintain a degree of plasticity that could be a strategic target for research aimed at treatment of memory disorders in aged humans. Images PMID:1763062

  20. Protection of rhesus monkeys against Soman and prevention of performance decrement by pretreatment with acetylcholinesterase. (Reannouncement with new availability information)

    SciTech Connect

    Maxwell, D.M.; Castro, C.A.; De La Hoz, D.M.; Gentry, M.K.; Gold, M.B.

    1992-12-31

    The ability of acetylcholinesterase from fetal bovine serum (FBS AChE) to protect against soman, a highly toxic organophosphorus (OP) compound, was tested in rhesus monkeys. Intravenous administration of FBS AChE produced a minimal behavioral effect on the serial probe recognition task, a sensitive test of cognitive function and short-term memory. Pharmacokinetic studies of injected FBS AChE indicated a plasma half-life of 40 hr for FBS AChE in monkeys. Both in vitro and in vivo titration of FBS AChE with soman produced a 1:1 stoichiometry between organophosphate-inhibited FBS AChE and the cumulative dose of the toxic stereoisomers of soman. Administration of FBS AChE protected monkeys against the lethal effects of up to 2.7 LD50 of soman and prevented any signs of organophosphate intoxication, e.g., excessive secretions, respiratory depression, muscle fasciculations, or convulsions. In addition, monkeys pretreated with FBS AChE were devoid of any behavioral incapacitation after soman challenge, as measured by the serial probe recognition task. Compared to the current multicomponent drug treatment against soman, which does not prevent the signs or the behavioral deficits resulting from OP intoxication, use of FBS AChE as a single pretreatment drug provides significantly effective protection against both the lethal and the behavioral effects of soman.... Pretreatment, Nonhuman primate, Performance decrements, Acetylcholinesterase, Soman, Nerve agents.

  1. Heterosexual, autosexual and social behavior of adult male rhesus monkeys with medial preoptic-anterior hypothalamic lesions.

    PubMed

    Slimp, J C; Hart, B L; Goy, R W

    1978-02-17

    Bilateral radiofrequency lesions were made in the medial preoptic-anterior hypothalamic (MP-AH) area of 6 adult male rhesus monkeys; 5 sham-lesioned subjects served as controls. Behavioral analysis consisted of observations on copulatory behavior, yawning, masturbation and some aspects of social behavior. MP-AH lesions reduced or completely eliminated the display of manual contacts of the partner, mounts, intromissions and ejaculations without interfering with masturbation. Yawning, a sexually dimorphic behavior, was not affected either, Measure of several social behaviors indicated no evidence of social withdrawal or other aberrance of social interactions, which might have led to the decline in heterosexual behavior. The results with regard to copulatory behavior were consistent with the effects of MP-AH lesions in rats, cats and dogs. In rhesus monkeys it appears as though the MP-AH region is specifically involved in the mediation of heterosexual copulation and is not vital to the performance of other forms of male sexual activity such as masturbation. Also the MP-AH is not critical for the display of all sexually dimorphic behaviors. The types of behavioral change in MP-AH lesioned subjects differed to some extent from those following castration, indicating that the effects of the lesions cannot be explained as basically that of functional castration.

  2. 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.

  3. 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.

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

    PubMed

    Hauser, Marc; Spaulding, Bailey

    2006-05-02

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

  6. 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.

  7. Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans.

    PubMed Central

    Philipp, M T; Aydintug, M K; Bohm, R P; Cogswell, F B; Dennis, V A; Lanners, H N; Lowrie, R C; Roberts, E D; Conway, M D; Karaçorlu, M

    1993-01-01

    We demonstrate that Borrelia burgdorferi infection in the rhesus monkey mimics the early and early disseminated phases of human Lyme disease. Clinical, bacteriological, immunological, and pathological signs of infection were investigated during 13 weeks after inoculation of the spirochete. Three animals were given B. burgdorferi (strain JD1) by needle inoculations, six animals were exposed to the bite of B. burgdorferi-infected Ixodes dammini ticks, and three animals were uninfected controls. B. burgdorferi could be recovered from all animals that were given the spirochete. Bacteria were detectable until week 6 postinoculation (p.i.) in blood, until week 8 p.i. in skin biopsies, and at 10 weeks p.i. in the conjunctiva of one of two animals which developed conjunctivitis. Erythema migrans (EM) appeared in one of the three animals infected by needle inoculation and in five of the six animals infected by ticks. Deep dermal perivascular lymphocytic infiltrations (characteristic of human EM) were observed in all animals showing EM clinically. Both EM and conjunctivitis were documented concomitantly with the presence of the spirochete. Lethargy, splenomegaly, and cerebrospinal fluid pleocytosis were also noted in some animals, but the direct connection of these signs with the infection was not shown. The appearance rate of immunoglobulin M and immunoglobulin G antibodies to B. burgdorferi, as well as the antigen spectra recognized, were remarkably similar to those seen in humans. Serum antibodies from infected animals were able to kill B. burgdorferi in vitro in the presence of rhesus complement. The rhesus monkey model appears to be useful for the investigation of the immunology and pathogenesis of Lyme disease and for the development of immunoprophylactic, diagnostic, and chemotherapeutic protocols. Images PMID:8514412

  8. Antioxidants, Oxyrase, and mitochondrial uncoupler 2,4-dinitrophenol improved postthaw survival of rhesus monkey sperm from ejaculates with low cryosurvival.

    PubMed

    Dong, Qiaoxiang; Tollner, Theodore L; Rodenburg, Sarah E; Hill, Dana L; VandeVoort, Catherine A

    2010-11-01

    Various antioxidant strategies such as supplementation of antioxidants, limiting oxygen concentration with Oxyrase, and reducing reactive oxygen species through mild mitochondrial uncoupling had statistically significant beneficial effects on sperm cryopreservation from rhesus monkeys with low cryoresistant ejaculates. Individuals or species that have higher sensitivity to cryodamage may derive the most benefit from these treatments.

  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.

  10. Radiation-Released Histamine in the Rhesus Monkey as Modified by Mast Cell Depletion and Antihistamine

    DTIC Science & Technology

    1975-06-01

    radiation of two untreated monkeys, four monkeys given chlorpheniramine 30 minutes before irradiation and four monkeys treated with 48/80 for four...antagonist, chlorpheniramine ’ (3 mg/kg), 30 minutes before irradiation. Experiment 3. Seven monkeys were given aminoguanidine and 30 minutes later the...4000-rad dose of ionizing radiation in animals receiving no treatment. When the animals were pretreated with chlorpheniramine , the histamine

  11. 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

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

    PubMed

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

    2015-10-01

    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.

  13. 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

  14. Genetically determined hypercholesterolemia in a rhesus monkey family due to a deficiency of the LDL receptor.

    PubMed

    Scanu, A M; Khalil, A; Neven, L; Tidore, M; Dawson, G; Pfaffinger, D; Jackson, E; Carey, K D; McGill, H C; Fless, G M

    1988-12-01

    A family of rhesus monkeys comprising a sire, a dam, and four male offspring were fed a cholesterol-free Purina Chow diet for several months. The sire, 431-J, and two of the offspring, B-8204 and B-8806, had persistent plasma cholesterol levels in the range of 100-130 mg/dl, whereas the dam, 766-I, and the two other offspring, B-1000 and B-7643, exhibited a marked hypercholesterolemia in the 250-300 mg/dl range associated with an elevation of plasma LDL and apoB. When fed for 12 weeks a diet containing 12.5% lard and 0.25% cholesterol, sire, dam, B-1000 and B-7643 exhibited a marked hypercholesterolemia (500-800 mg/dl range), whereas B-8204 and B-8806 developed only a modest hypercholesterolemia (200-250 mg/dl). All animals were Lp[a]+. Skin fibroblasts from each animal and from control cells were grown in 10% fetal calf serum, transferred to 10% lipoprotein-deficient serum for 48 hr, and then incubated at 4 degrees C or 37 degrees C with 125I-labeled Lp[a]-free LDL. The fibroblasts from dam and offspring B-1000 and B-7643 bound and internalized 125I-labeled LDL less efficiently than control cells. Mathematical analyses of the 4 degrees C binding data indicated that there were no significant differences in LDL binding affinity between test and control cells suggesting that cells from the animals with a spontaneous hypercholesterolemia had a decreased number of LDL receptors. This conclusion was supported by the results of ligand and immunoblot analyses carried out on cell lysates separated by gradient gel electrophoresis. We conclude that a genetically determined LDL receptor deficiency was responsible, in part, for the spontaneous hypercholesterolemia observed in three out of the six family members and that this deficiency accounted for the hyperresponsiveness to a dietary fat and cholesterol challenge by the dam and the two offspring, B-1000 and B-7643. The hyperresponsiveness noted in the sire that had no evidence for LDL-receptor deficiency illustrates that

  15. 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

  16. Changes in hippocampal ultrastructure and vimentin expression in rhesus monkeys following selective deep hypothermia and blood occlusion.

    PubMed

    Li, B C; Fu, X; Niu, X Q; Fan, Y D; Xu, W; Zhao, X X; Pu, J

    2015-01-30

    Previous studies have shown that selective cerebral profound hypothermia combined with antegrade cerebral perfusion can improve resistance to cerebral hypoxia-ischemia in monkeys. The aim of this study was to observe the effect of selective cerebral profound hypothermia on the ultrastructure and vimentin expression in monkey hippocampi after severe cerebral ischemia. Eight healthy adult rhesus monkeys were randomly divided into two groups: profound hypothermia (N = 5) and normothermia (N = 3). Monkeys in the profound hypothermia group underwent bilateral carotid artery and jugular vein occlusion for 10 minutes at room temperature. Ringer's solution at 4°C was then perfused through the right internal carotid artery and out of the right jugular vein, maintaining the brain temperature below 18°C. Sixty minutes later, cerebral blood flow was restored. The normothermia group underwent all procedures with the exception that the Ringer's solution was 37°C during perfusion. All animals in the profound hypothermia group were successfully resuscitated. No significant abnormalities of hippocampal morphology or ultrastructure were observed. In contrast, no monkeys were alive after perfusion in the normothermia group and they had abnormal hippocampal morphology and ultrastructure to different extents. Vimentin expression in the hippocampus was significantly lower in the profound hypothermia group (47.88% ± 1.66) than the normothermia group (79.51% ± 1.00; P < 0.01). We conclude that selective cerebral profound hypothermia following 10-min occlusion of the bilateral common carotid arteries was able to downregulate vimentin expression in the hippocampus and protect it from severe cerebral ischemia.

  17. Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents.

    PubMed Central

    Lane, M A; Baer, D J; Rumpler, W V; Weindruch, R; Ingram, D K; Tilmont, E M; Cutler, R G; Roth, G S

    1996-01-01

    Many studies of caloric restriction (CR) in rodents and lower animals indicate that this nutritional manipulation retards aging processes, as evidenced by increased longevity, reduced pathology, and maintenance of physiological function in a more youthful state. The anti-aging effects of CR are believed to relate, at least in part, to changes in energy metabolism. We are attempting to determine whether similar effects occur in response to CR in nonhuman primates. Core (rectal) body temperature decreased progressively with age from 2 to 30 years in rhesus monkeys fed ad lib (controls) and is reduced by approximately 0.5 degrees C in age-matched monkeys subjected to 6 years of a 30% reduction in caloric intake. A short-term (1 month) 30% restriction of 2.5-year-old monkeys lowered subcutaneous body temperature by 1.0 degrees C. Indirect calorimetry showed that 24-hr energy expenditure was reduced by approximately 24% during short-term CR. The temporal association between reduced body temperature and energy expenditure suggests that reductions in body temperature relate to the induction of an energy conservation mechanism during CR. These reductions in body temperature and energy expenditure are consistent with findings in rodent studies in which aging rate was retarded by CR, now strengthening the possibility that CR may exert beneficial effects in primates analogous to those observed in rodents. PMID:8633033

  18. 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.

  19. Transplantation of cultured rhesus monkey vascular endothelial cells to allogeneic cornea concomitant with stripping of Descemet's membrane

    PubMed Central

    Zhu, Qin; Wu, Min; Sun, Xiaomei; Zhang, Wenjia; Hu, Zhulin; Liu, Hai

    2015-01-01

    Context: In cases of damaged corneal endothelium cells (CECs) of the eye, transplantation of cultured vascular endothelial cells (VECs) may be a viable method to restore transparency. Aims: To evaluate the viability of replacing damaged primate CECs with cultured allogeneic VECs. Subjects and Methods: Rhesus monkey VECs (RMVECs) were cultured and proliferating cells were labeled with bromodeoxyuridine (BrdU) in vitro. RMs of the experimental group (n = 6) underwent manual Descemettt membrane stripping with transplantation of RMVECs labeled with BrdU; those in the control group received manual Descemetnt membrane stripping without transplantation. Postoperative evaluations included the transparency and appearance of the corneal graft; distribution and ultrastructural changes of RMVECs on the inner surface of the cornea using scanning and transmission electron microscopy, and immunohistological identification of BrdU. Results: At 90 days postsurgery, the corneal grafts of the monkeys in the experimental group retained better transparency than those of the controls, without corneal neovascularization or bullous keratopathy. A layer of cells with positive BrdU staining was found on the posterior surface of the treated corneas in the experimental group, while there was no VEC structure in corneal grafts from the monkeys of the control group. Conclusions: RMVECs can grow on the posterior surface of the cornea without Descemet's membrane. Cultured and transplanted RMVECs appeared similar in ultrastructure. VECs can provide a barrier to maintain corneal dehydration and transparency to some extent. PMID:26576525

  20. Rhesus monkeys (Macaca mulatta) show robust primacy and recency in memory for lists from small, but not large, image sets

    PubMed Central

    Basile, Benjamin M.; Hampton, Robert R.

    2010-01-01

    The combination of primacy and recency produces a U-shaped serial position curve typical of memory for lists. In humans, primacy is often thought to result from rehearsal, but there is little evidence for rehearsal in nonhumans. To further evaluate the possibility that rehearsal contributes to primacy in monkeys, we compared memory for lists of familiar stimuli (which may be easier to rehearse) to memory for unfamiliar stimuli (which are likely difficult to rehearse). Six rhesus monkeys saw lists of five images drawn from either large, medium, or small image sets. After presentation of each list, memory for one item was assessed using a serial probe recognition test. Across four experiments, we found robust primacy and recency with lists drawn from small and medium, but not large, image sets. This finding is consistent with the idea that familiar items are easier to rehearse and that rehearsal contributes to primacy, warranting further study of the possibility of rehearsal in monkeys. However, alternative interpretations are also viable and are discussed. PMID:20035843

  1. Population variation in neuroendocrine activity is associated with behavioral inhibition and hemispheric brain structure in young rhesus monkeys.

    PubMed

    Short, Sarah J; Lubach, Gabriele R; Shirtcliff, Elizabeth A; Styner, Martin A; Gilmore, John H; Coe, Christopher L

    2014-09-01

    Population variation in hypothalamic-pituitary-adrenal (HPA) activity and reactivity was assessed in a healthy sample of 48 juvenile rhesus monkeys. Cluster analysis of the HPA profiles revealed four distinct neuroendocrine phenotypes based on six indices of HPA functioning. Behavioral reactivity was also evaluated in response to novel stimuli, and revealed marked differences between animals in the highest- and lowest-cortisol clusters. Specifically, animals in the high-cortisol cluster showed larger stress-induced cortisol responses and blunted feedback sensitivity to dexamethasone. They were also emotionally reactive, displayed more aggressive behaviors, and were less likely to approach novel objects. In contrast, monkeys in the low-cortisol cluster were more likely to approach and explore novel objects. Representative animals with high or low cortisol profiles were scanned with Magnetic Resonance Imaging to evaluate structural differences in global and regional gray matter (GM) and white matter (WM) volumes. Monkeys with higher cortisol reactivity evinced less hemispheric brain asymmetry, due to decreased GM in the right hemisphere. Stress reactivity was inversely related to global GM and positively related to total cerebrospinal fluid volume. This inverse relationship was also observed in several stress-sensitive regions, including prefrontal and frontal cortices. Our study demonstrates that population variation in pituitary-adrenal activity is related to behavioral disposition and cerebral structure in this nonhuman primate species.

  2. Monkeying around with HIV vaccines: using rhesus macaques to define 'gatekeepers' for clinical trials.

    PubMed

    Shedlock, Devon J; Silvestri, Guido; Weiner, David B

    2009-10-01

    Rhesus macaques are an important animal model for the study of human disease and the development of vaccines against HIV and AIDS. HIV vaccines have been benchmarked in rhesus macaque preclinical challenge studies using chimeric viruses made up of parts of HIV and simian immunodeficiency viruses. However, the lack of efficacy in a recent clinical trial calls for a re-evaluation of the scientific assumptions regarding the predictive value of using data generated from rhesus macaques as a 'gatekeeper' for the advancement of candidate vaccines into the clinic. In this context, there is significant consensus among HIV vaccinologists that next-generation HIV vaccines must generate 'better' immunity in rhesus macaques than clinically unsuccessful vaccines generated using validated assays. Defining better immunity is the core challenge of HIV vaccine development in this system and is the focus of this Review.

  3. The role of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in comparison with whole egg yolk for sperm cryopreservation in rhesus monkeys.

    PubMed

    Dong, Qiao-Xiang; Rodenburg, Sarah E; Hill, Dana; Vandevoort, Catherine A

    2011-05-01

    Low-density lipoprotein (LDL) extracted from hen egg yolk has recently been considered to be superior to whole egg yolk in sperm cryopreservation of various animal species. Meanwhile, there was a notion that high-density lipoprotein (HDL) in egg yolk may have a negative effect on post-thaw survival. The role of LDL and HDL in sperm cryopreservation of rhesus monkeys has not been explored. The present study evaluates their effect in comparison with egg yolk with or without the addition of permeable cryoprotectant (glycerol) on sperm cryopreservation of rhesus macaques. In addition, various additives intended to change the lipid composition of LDL-sperm membrane complex have also been tested for their effectiveness in preserving post-thaw viability. Our findings indicated that LDL is the main component in egg yolk that is responsible for its protective role for sperm cryopreservation in rhesus monkeys. Regardless of the presence or absence of glycerol, the protective role of LDL is similar to that of egg yolk and we did not observe any superiority in post-thaw survival with LDL when compared to egg yolk. Modifying the lipid composition of LDL-sperm membrane complex with the addition of cholesterol, cholesterol loaded cyclodextrin and phosphatidylcholine also did not yield any improvements in post-thaw survival; while addition of methyl-β-cyclodextrin reduced post-thaw motility. HDL plays a neutral role in sperm cryopreservation of rhesus monkeys. The present study suggests that egg yolk may still hold advantages when compared with LDL as effective components in extenders for sperm cryopreservation in rhesus monkeys.

  4. 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.

  5. Effects of Quetiapine Treatment on Cocaine Self-Administration and Behavioral Indices of Sleep in Adult Rhesus Monkeys

    PubMed Central

    Brutcher, Robert E.; Nader, Michael A.

    2014-01-01

    Rationale Clinical literature suggests a link between substance abuse and sleep disturbances. Quetiapine, an atypical antipsychotic has shown efficacy in treating sleep disturbances, with clinical studies showing promise for quetiapine as a treatment for cocaine abuse. Objective The goal of this study was to examine the effects of quetiapine on cocaine self-administration and behavioral indices of sleep in monkeys. Methods Seven adult male rhesus monkeys, fitted with Actical® activity monitors, were trained to respond under a choice paradigm of food (1.0-g pellets) and cocaine (0.003–0.3 mg/kg per injection) presentation. First, monkeys received acute pretreatment (45 min) with quetiapine (25–75 mg, p.o.) prior to choice sessions; three cocaine doses were studied in combination with quetiapine. Next, the effect of chronic (14–16 days) quetiapine treatment (25–250 mg, p.o., BID) was examined in combination with the lowest preferred cocaine dose (≥ 80% cocaine choice). Behavioral indices of sleep, based on activity measures obtained during lights-out, were recorded throughout the study. Results Acute quetiapine decreased cocaine choice in four of the seven monkeys. Chronic quetiapine treatment resulted in initial decreases, but tolerance developed to these effects. Acute doses of quetiapine did not improve sleep efficiency the following night, nor did chronic quetiapine. The first night after discontinuing quetiapine treatment resulted in significant decreases in sleep efficiency and increases in nighttime activity. Conclusions These findings do not offer support for the use of quetiapine as a monotherapy for treatment of cocaine abuse nor as an adjunct therapy to treat sleep disturbances associated with stimulant abuse. PMID:25030802

  6. Open reading frames carried on UL/b' are implicated in shedding and horizontal transmission of rhesus cytomegalovirus in rhesus monkeys.

    PubMed

    Oxford, Kristie L; Strelow, Lisa; Yue, Yujuan; Chang, W L William; Schmidt, Kimberli A; Diamond, Don J; Barry, Peter A

    2011-05-01

    Implicit with the use of animal models to test human cytomegalovirus (HCMV) vaccines is the assumption that the viral challenge of vaccinated animals reflects the anticipated virus-host interactions following exposure of vaccinated humans to HCMV. Variables of animal vaccine studies include the route of exposure to and the titer of challenge virus, as well as the genomic coding content of the challenge virus. This study was initiated to provide a better context for conducting vaccine trials with nonhuman primates by determining whether the in vivo phenotype of culture-passaged strains of rhesus cytomegalovirus (RhCMV) is comparable to that of wild-type RhCMV (RhCMV-WT), particularly in relation to the shedding of virus into bodily fluids and the potential for horizontal transmission. Results of this study demonstrate that two strains containing a full-length UL/b' region of the RhCMV genome, which encodes proteins involved in epithelial tropism and immune evasion, were persistently shed in large amounts in bodily fluids and horizontally transmitted, whereas a strain lacking a complete UL/b' region was not shed or transmitted to cagemates. Shedding patterns exhibited by strains encoding a complete UL/b' region were consistent with patterns observed in naturally infected monkeys, the majority of whom persistently shed high levels of virus in saliva for extended periods of time after seroconversion. Frequent viral shedding contributed to a high rate of infection, with RhCMV-infected monkeys transmitting virus to one naïve animal every 7 weeks after introduction of RhCMV-WT into an uninfected cohort. These results demonstrate that the RhCMV model can be designed to rigorously reflect the challenges facing HCMV vaccine trials, particularly those related to horizontal transmission.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. The association of depressed angiogenic factors with reduced capillary density in the Rhesus monkey model of myocardial ischemia.

    PubMed

    Zhang, Wenjing; Zhao, Xinmei; Xiao, Ying; Chen, Jianmin; Han, Pengfei; Zhang, Jingyao; Fu, Haiying; James Kang, Y

    2016-07-13

    Depressed capillary density is associated with myocardial ischemic infarction, in which hypoxia-inducible factor 1α (HIF-1α) is increased. The present study was undertaken to examine changes in the angiogenic factors whose expression is regulated by HIF-1 and their relation to the depressed capillary density in the Rhesus monkey model of myocardial ischemic infarction. Male Rhesus monkeys 2-3 years old were subjected to myocardial ischemia by permanent ligation of left anterior descending (LAD) artery leading to the development of myocardial infarction. Eight weeks after LAD ligation, copper concentrations, myocardial histological changes and capillary density were examined, along with Western blot and immunohistochemical analysis of angiogenic factors and detection of HIF-1 activity. Capillary density was significantly decreased but the concentrations of HIF-1α and HIF-1β were significantly increased in the infarct area. However, the levels of mRNA and protein for VEGF and VEGFR1 were significantly decreased. Other HIF-1 regulated angiogenic factors, including Tie-2, Ang-1 and FGF-1, were also significantly depressed, but vascular destabilizing factor Ang-2 was significantly increased. Copper concentrations were depressed in the infarct area. Copper-independent HIF-1 activity was increased shown by the elevated mRNA level of IGF-2, a HIF-1 target gene. Removal of copper by a copper chelator, tetraethylenepentamine, from primary cultures of neonatal rat cardiomyocytes also suppressed the expression of HIF-1 regulated VEGF and BNIP3, but not IGF-2. The data suggest that under ischemic conditions, copper loss suppressed the expression of critical angiogenic genes regulated by HIF-1, but did not affect copper-independent HIF-1 activation of gene expression. This copper-dependent dysregulation of angiogenic gene expression would contribute to the pathogenesis of myocardial ischemic infarction.

  13. A within-subject assessment of the discriminative stimulus and reinforcing effects of self-administered cocaine in rhesus monkeys

    PubMed Central

    Martelle, Jennifer L.

    2009-01-01

    Rationale Drug discrimination (DD) and drug self-administration (SA) are frequently used preclinical assays. All preclinical studies with cocaine have examined the discriminative stimulus (SD) and reinforcing (SR) effects in separate groups of subjects. Objective The objective of the study is to train drug-naïve rhesus macaques to discriminate self-administered cocaine from saline and to assess SD and SR effects using a within-subjects design. Materials and methods Adult male rhesus monkeys (n=4) were trained to self-administer cocaine (0.1 mg/kg per injection) under a progressive-ratio (PR) reinforcement schedule. Next, they were trained to discriminate self-administered cocaine (0.45 or 0.56 mg/kg) or saline under a fixed-ratio (FR) 50 schedule of food presentation. The final schedule combined DD and SA into a multiple [chained FR 50 SA (cocaine or saline), food-reinforced DD] and PR SA schedule. Results Each subject acquired SA under a PR schedule with significant differences in breakpoint between saline and cocaine evident by session 5. Self-administered cocaine was established as an SD, such that 80% of responding before delivery of the first reinforcer and 90% of all responding occurred on the injection-appropriate lever. In all monkeys, there was at least one cocaine dose that did not engender cocaine-appropriate responding during DD (i.e., <20% cocaine-appropriate responding) yet functioned as a reinforcer during PR SA, suggesting that cocaine-like SD effects are not necessary for cocaine reinforcement. Conclusions This within-subject model may provide new information related to the behavioral mechanisms of action leading to the high abuse potential of cocaine; such information may lead to novel pharmacological treatment strategies for addiction. PMID:18807249

  14. Functional consequences of age-related morphologic changes to pyramidal neurons of the rhesus monkey prefrontal cortex.

    PubMed

    Coskren, Patrick J; Luebke, Jennifer I; Kabaso, Doron; Wearne, Susan L; Yadav, Aniruddha; Rumbell, Timothy; Hof, Patrick R; Weaver, Christina M

    2015-04-01

    Layer 3 (L3) pyramidal neurons in the lateral prefrontal cortex (LPFC) of rhesus monkeys exhibit dendritic regression, spine loss and increased action potential (AP) firing rates during normal aging. The relationship between these structural and functional alterations, if any, is unknown. To address this issue, morphological and electrophysiological properties of L3 LPFC pyramidal neurons from young and aged rhesus monkeys were characterized using in vitro whole-cell patch-clamp recordings and high-resolution digital reconstruction of neurons. Consistent with our previous studies, aged neurons exhibited significantly reduced dendritic arbor length and spine density, as well as increased input resistance and firing rates. Computational models using the digital reconstructions with Hodgkin-Huxley and AMPA channels allowed us to assess relationships between demonstrated age-related changes and to predict physiological changes that have not yet been tested empirically. For example, the models predict that in both backpropagating APs and excitatory postsynaptic currents (EPSCs), attenuation is lower in aged versus young neurons. Importantly, when identical densities of passive parameters and voltage- and calcium-gated conductances were used in young and aged model neurons, neither input resistance nor firing rates differed between the two age groups. Tuning passive parameters for each model predicted significantly higher membrane resistance (R m ) in aged versus young neurons. This R m increase alone did not account for increased firing rates in aged models, but coupling these R m values with subtle differences in morphology and membrane capacitance did. The predicted differences in passive parameters (or parameters with similar effects) are mathematically plausible, but must be tested empirically.

  15. 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.

  16. 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.

  17. Cynomolgus and rhesus monkey visual pigments. Application of Fourier transform smoothing and statistical techniques to the determination of spectral parameters

    PubMed Central

    1987-01-01

    Microspectrophotometric measurements were performed on 217 photoreceptors from cynomolgus, Macaca fascicularis, and rhesus, M. mulatta, monkeys. The distributions of cell types, for rods and blue, green, and red cones were: 52, 12, 47, and 44, respectively, for the cynomolgus, and 22, 4, 13, and 13 for the rhesus. Visual cells were obtained fresh (unfixed), mounted in various media (some containing 11- cis-retinal), and then located visually under dim red (650 nm) illumination. Absolute absorbance (A), linear dichroism (LD), and bleaching difference (BD) absorbance spectra were recorded through the sides of outer segments. The spectra were subjected to rigorous selection criteria, followed by digital averaging and Fourier transform filtering. Statistical methods were also applied to the accepted samples in the estimation of population means and variances. The wavelength of mean peak absorbance (lambda max) and the standard error at 95% certainty of the rod and blue, green, and red cone pigments in cynomolgus were 499.7 +/- 2.5, 431.4 +/- 4.2, 533.9 +/- 2.4, and 565.9 +/- 2.8 nm, respectively. The rhesus pigments were statistically indistinguishable from the cynomolgus, having lambda max of approximately 500, 431, 534, and 566 nm. Statistical tests did not reveal the presence of a lambda max subpopulation (i.e., anomalous pigments). The bandwidth of each alpha-band was determined in two segments, giving rise to the longwave half-density (LWHDBW), shortwave half-density (SWHDBW), and total half-density (THDBW) bandwidths. The LWHDBW was found to have the smallest variance. Both the LWHDBW and the THDBW showed linear dependence on the peak wavenumber (lambda max)-1 for the four macaque pigments. PMID:3598558

  18. 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

  19. 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…

  20. Influence of Amplitude, Starting Point, and Age on First- and Second-Order Dynamics of Edinger-Westphal–Stimulated Accommodation in Rhesus Monkeys

    PubMed Central

    Baumeister, Martin; Wendt, Mark

    2010-01-01

    Purpose. In humans, accommodative and disaccommodative dynamics depend on response amplitude and starting point. The purpose of this study was to determine the influence of amplitude and starting point on open-loop accommodative dynamics in Edinger-Westphal (EW)-stimulated, anesthetized rhesus monkeys of different ages. Methods. One eye each of two younger and two older iridectomized rhesus monkeys, (aged 6.8, 8.9, 15.0, and 16.3 years) were studied. The experiment was repeated in one eye of one younger monkey. Lens thickness changes were recorded by dynamic ultrasound biometry at 100 Hz. Stimuli used produced accommodative responses: (1) starting from baseline with increasing amplitudes; (2) from increasing starting points to maximum accommodation; and (3) from increasing starting points with a constant amplitude of 1 D. The lens thickness measurements were converted into accommodation and velocities and accelerations of the responses were determined by using a two-point difference algorithm. Results. Maximum accommodative amplitudes ranged from 4.68 to 6.37 D in the older monkeys and 9.33 to 11.59 D in the younger monkeys. The peak velocity of accommodation and disaccommodation increased linearly with response amplitude. Peak velocity and peak acceleration of accommodation and disaccommodation were independent of the response starting point. Subtle variations in disaccommodative response peak velocities were found to vary with age. Conclusions. The results suggest that, in anesthetized rhesus monkeys, disaccommodative rather than accommodative dynamics may be more sensitive to age-related changes and that, unlike in conscious human subjects, the starting configuration of the accommodative plant has little influence on accommodative dynamics. PMID:20484591

  1. 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.

  2. 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

  3. 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.

  4. A calorie-restricted diet decreases brain iron accumulation and preserves motor performance in old rhesus monkeys

    PubMed Central

    Kastman, EK; Willette, AA; Coe, CL; Bendlin, BB; Kosmatka, KJ; McLaren, DG; Xu, G; Canu, E; Field, AS; Alexander, AL; Voytko, ML; Beasley, TM; Colman, RJ; Weindruch, R; Johnson, SC

    2010-01-01

    Caloric restriction (CR) reduces the pathological effects of aging and extends the lifespan in many species, including nonhuman primates, although the effect on the brain is less well characterized. We used two common indicators of aging, motor performance speed and brain iron deposition measured in vivo using MRI, to determine the potential effect of CR on elderly rhesus macaques eating restricted (n = 24, 13 males, 11 females) and standard diets (n= 17, 8 males, 9 females). Both the CR and control monkeys showed age-related increases in iron concentrations in globus pallidus (GP) and substantia nigra (SN), although the CR group had significantly less iron deposition in the GP, SN, red nucleus and temporal cortex. A Diet x Age interaction revealed that CR modified age-related brain changes, evidenced as attenuation in the rate of iron accumulation in basal ganglia and parietal, temporal, and perirhinal cortex. Additionally, control monkeys had significantly slower fine motor performance on the Movement Assessment Panel, which was negatively correlated with iron accumulation in left SN and parietal lobe, although CR animals did not show this relationship. Our observations suggest that the CR induced benefit of reduced iron deposition and preserved motor function may indicate neural protection similar to effects described previously in aging rodent and primate species. PMID:20534842

  5. 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.

  6. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in Rhesus monkeys exposed to ozone

    SciTech Connect

    Castleman, W.L.; Dungworth, D.L.; Schwartz, L.W.; Tyler, W.S.

    1980-03-01

    The pathogenesis of acute respiratory bronchiolitis was examined in Rhesus monkeys exposed to 0.8 ppM ozone for 4 to 50 hours. Epithelial injury and renewal were qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy as well as by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4 to 12 hours of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 hours of exposure, and the highest labeling index (18%) was measured after 50 hours of exposure. Most (67 to 80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20 to 33% were Type 2 epithelial cells. After 50 hours of exposure the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 hours and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. The results indicate that Type 1 epithelial cells lining respiratory bronchioles are the cell types most sensitive to injury and that both cuboidal bronchiolar epithelial cells and Type 2 epithelial cells function as stem cells in epithelial renewal.

  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. Immunogenicity and Protective Efficacy in a Rhesus Monkey Model of Vaccine Ac NFU1(S-) MRC Against Primary Type 2 Herpes Simplex Virus Infection

    PubMed Central

    Skinner, G. R. B.; Buchan, A.; Williams, D.; Marsden, J.; Hartley, C.; Wilbanks, G.; Turyk, M.; Namkoong, E. S.

    1982-01-01

    Adult and juvenile Rhesus monkeys were vaccinated with sub-unit formaldehyde-inactivated vaccine Ac NFU1(S-) MRC; no local or systemic side-effects followed vaccination. Vaccinated monkeys developed neutralizing and immunoprecipitating antibody to both type 1 and 2 herpes simplex virus. Antibody levels declined with time but were re-stimulated after virus challenge and to a lesser extent after attempted virus reactivation. There was evidence of protection against s.c. challenge with live type 2 herpes simplex virus. PMID:6295430

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

    PubMed

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

    2014-04-01

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

  10. 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

  11. 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

  12. Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys.

    PubMed

    Banks, Matthew L; Smith, Douglas A; Blough, Bruce E

    2016-04-01

    The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate 'agonist' medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like 'agonist' effects remains unknown. The aim of the present study was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. The potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, at least 90%, methamphetamine-like effects. 2R,3R-Hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like 'agonist' effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out.

  13. l-theanine attenuates abstinence signs in morphine-dependent rhesus monkeys and elicits anxiolytic-like activity in mice.

    PubMed

    Wise, Laura E; Premaratne, Ishani D; Gamage, Thomas F; Lichtman, Aron H; Hughes, Larry D; Harris, Louis S; Aceto, Mario D

    2012-12-01

    l-theanine, 2-amino-4-(ethylcarbamoyl) butyric acid, an amino acid found in green tea (Camellia sinensis), is sold in the United States as a dietary supplement to reduce stress and improve cognition and mood. The observations that l-theanine has been shown to inhibit caffeine's stimulatory effects and that caffeine produces precipitated withdrawal signs in opioid-addicted monkeys and some opioid withdrawal signs in some normal monkeys, suggest that l-theanine may suppress opioid withdrawal signs. Additionally, l-theanine produces anxiolytic effects in humans indicating that it has anti-anxiety properties. Thus, in these studies we determined whether l-theanine attenuates opioid-withdrawal signs in morphine-dependent rhesus monkeys, a model for spontaneous opioid withdrawal in human opioid addicts. We also evaluated whether l-theanine decreases anxiety-like behavior in mice, using the elevated plus maze and marble burying assays. l-theanine significantly attenuated designated opioid withdrawal signs, including fighting, rigid abdominal muscles, vocalizing on palpation of abdomen, pacing, retching, wet-dog shakes, and masturbation. It had a relatively quick onset of action that persisted for at least 2.5h. l-theanine also produced anxiolytic-like effects in the elevated plus maze and the marble burying assay in naïve mice at doses that did not significantly affect motor behavior. The results of these studies suggest that l-theanine may be useful in the pharmacotherapy of treating opioid withdrawal as well as anxiety-associated behaviors.

  14. Rhesus monkeys employ a procedural strategy to reduce working memory load in a self-ordered spatial search task.

    PubMed

    Taffe, Michael A; Taffe, William J

    2011-09-21

    Several nonhuman primate species have been reported to employ a distance-minimizing, traveling salesman-like, strategy during foraging as well as in experimental spatial search tasks involving lesser amounts of locomotion. Spatial sequencing may optimize performance by reducing reference or episodic memory loads, locomotor costs, competition or other demands. A computerized self-ordered spatial search (SOSS) memory task has been adapted from a human neuropsychological testing battery (CANTAB, Cambridge Cognition, Ltd) for use in monkeys. Accurate completion of a trial requires sequential responses to colored boxes in two or more spatial locations without repetition of a previous location. Marmosets have been reported to employ a circling pattern of search, suggesting spontaneous adoption of a strategy to reduce working memory load. In this study the SOSS performance of rhesus monkeys was assessed to determine if the use of a distance-minimizing search path enhances accuracy. A novel strategy score, independent of the trial difficulty and arrangement of boxes, has been devised. Analysis of the performance of 21 monkeys trained on SOSS over 2 years shows that a distance-minimizing search strategy is associated with improved accuracy. This effect is observed within individuals as they improve over many cumulative sessions of training on the task and across individuals at any given level of training. Erroneous trials were associated with a failure to deploy the strategy. It is concluded that the effect of utilizing the strategy on this locomotion-free, laboratory task is to enhance accuracy by reducing demands on spatial working memory resources.

  15. Duration of airborne-manganese exposure in rhesus monkeys is associated with brain regional changes in biomarkers of neurotoxicity.

    PubMed

    Erikson, Keith M; Dorman, David C; Lash, Lawrence H; Aschner, Michael

    2008-05-01

    Juvenile (20-24-month-old) rhesus monkeys were exposed to airborne-manganese sulfate (MnSO(4)) 1.5 mg Mn/m(3) (6h/day, 5 days/week) for 15 or 33 days, or for 65 days followed by a 45 or 90 days post-exposure recovery period, or air. We assessed biochemical endpoints indicative of oxidative stress and excitotoxicity in the cerebellum, frontal cortex, caudate, globus pallidus, olfactory cortex, and putamen. Glutamine synthetase (GS), glutamate transporters (GLT-1 and GLAST) and tyrosine hydroxylase (TH) protein levels, metallothionein (MT), GLT-1, GLAST, TH and GS mRNA levels, and total glutathione (GSH) levels were determined for all brain regions. Exposure to Mn significantly decreased MT mRNA in the caudate (vs. air-exposed controls). This depression persisted at least 90 days post-exposure. In contrast, putamen MT mRNA levels were unaffected by Mn exposure. GLT-1 and GLAST were relatively unaffected by short term Mn exposure, except in the globus pallidus where exposure for 33 days led to decreased protein levels, which persisted after 45 days of recovery for both proteins and 90 days of recovery in the case of GLAST. Exposure to 1.5 mg Mn/m(3) caused a significant decrease in GSH levels in the caudate and increased GSH levels in the putamen of monkey exposed for 15 and 33 days with both effects persisting at least 90 days post-exposure. Finally, TH protein levels were significantly lowered in the globus pallidus of the monkeys exposed for 33 days but mRNA levels were significantly increased in this same region. Overall, the nonhuman primate brain responds to airborne Mn in a heterogeneous manner and most alterations in these biomarkers of neurotoxicity are reversible upon cessation of Mn exposure.

  16. Methamphetamine-like discriminative stimulus effects of bupropion and its two hydroxy metabolites in male rhesus monkeys

    PubMed Central

    Banks, Matthew L.; Smith, Douglas A.; Blough, Bruce E.

    2016-01-01

    The dopamine transporter (DAT) inhibitor and nicotinic acetylcholine (nACh) receptor antagonist bupropion is being investigated as a candidate ‘agonist’ medication for methamphetamine addiction. In addition to its complex pharmacology, bupropion also has two distinct pharmacologically active metabolites. However, the mechanism by which bupropion produces methamphetamine-like ‘agonist’ effects remains unknown. The present aim was to determine the role of DAT inhibition, nACh receptor antagonism, and the hydroxybupropion metabolites in the methamphetamine-like discriminative stimulus effects of bupropion in rhesus monkeys. In addition, varenicline, a partial agonist at the nACh receptor, and risperidone, a dopamine antagonist, were tested as controls. Monkeys (n=4) were trained to discriminate 0.18 mg/kg intramuscular methamphetamine from saline in a two-key food-reinforced discrimination procedure. Potency and time course of methamphetamine-like discriminative stimulus effects were determined for all compounds. Bupropion, methylphenidate, and 2S,3S-hydroxybupropion produced full, ≥90%, methamphetamine-like effects. 2R,3R-hydroxybupropion, mecamylamine, and nicotine also produced full methamphetamine-like effects, but drug potency was more variable between monkeys. Varenicline produced partial methamphetamine-like effects, whereas risperidone did not. Overall, these results suggest DAT inhibition as the major mechanism of the methamphetamine-like ‘agonist’ effects of bupropion, although nACh receptor antagonism appeared, at least partially, to contribute. Furthermore, the contribution of the 2S,3S-hydroxybupropion metabolite could not be completely ruled out. PMID:26886209

  17. 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 administration. Although administration of DM CocE produced increases in anti-CocE antibodies, they did not appear to have a neutralizing effect on the capacity of DM CocE to reverse the cardiovascular effects of cocaine. In conclusion, these findings in monkeys provide strong evidence to suggest that highly efficient cocaine esterases, such as DM CocE, can provide a potential therapeutic option for treatment of acute cocaine intoxication in humans.

  18. Rhesus Monkeys (Macaca mulatta) Adaptively Adjust Information Seeking in Response to Information Accumulated

    PubMed Central

    Tu, Hsiao-Wei; Pani, Alex A.; Hampton, Robert R.

    2015-01-01

    Metacognition consists of monitoring and control processes. Monitoring has been inferred when nonhumans use a “decline test” response to selectively escape difficult test trials. Cognitive control has been inferred from selective information seeking behavior by nonhumans ignorant of needed knowledge. Here we describe a computerized paradigm that extends previous work and begins to assess dynamic interactions between monitoring and control. Monkeys classified images as containing birds, fish, flowers, or people. To-be-classified images were initially masked, and monkeys were trained to gradually reveal the images by touching a “reveal button.” Monkeys could choose to classify images at any time or to reveal more of the images. Thus, they had the opportunity to assess when enough of an image had been revealed to support accurate classification. In Experiment 1, monkeys made more reveal responses before classifying when smaller amounts of the image were revealed by each button touch. In Experiment 2, to-be-classified images were shrunken and covered by one critical blocker among other blockers that did not provide information when removed. Monkeys made more reveal responses as the critical blocker was removed later in the trial. In Experiment 3, monkeys were re-presented with previously classified images with either more or fewer blockers obscuring the image than was the case when they chose to classify that image previously. Monkeys made more reveal responses when information was insufficient compared to when it was excessive. These results indicate that monkeys dynamically monitor evolving decision processes and adaptively collect information as necessary to maintain accuracy. PMID:26280597

  19. Effects of Long-Wavelength Lighting on Refractive Development in Infant Rhesus Monkeys

    PubMed Central

    Smith, Earl L.; Hung, Li-Fang; Arumugam, Baskar; Holden, Brien A.; Neitz, Maureen; Neitz, Jay

    2015-01-01

    Purpose Differences in the spectral composition of lighting between indoor and outdoor scenes may contribute to the higher prevalence of myopia in children who spend low amounts of time outdoors. Our goal was to determine whether environments dominated by long-wavelength light promote the development of myopia. Methods Beginning at 25 ± 2 days of age, infant monkeys were reared with long-wavelength-pass (red) filters in front of one (MRL, n = 6) or both eyes (BRL, n = 7). The filters were worn continuously until 146 ± 7 days of age. Refractive development, corneal power, and vitreous chamber depth were assessed by retinoscopy, keratometry, and ultrasonography, respectively. Control data were obtained from 6 monkeys reared with binocular neutral density (ND) filters and 33 normal monkeys reared with unrestricted vision under typical indoor lighting. Results At the end of the filter-rearing period, the median refractive error for the BRL monkeys (+4.25 diopters [D]) was significantly more hyperopic than that for the ND (+2.22 D; P = 0.003) and normal monkeys (+2.38 D; P = 0.0001). Similarly, the MRL monkeys exhibited hyperopic anisometropias that were larger than those in normal monkeys (+1.70 ± 1.55 vs. −0.013 ± 0.33 D, P < 0.0001). The relative hyperopia in the treated eyes was associated with shorter vitreous chambers. Following filter removal, the filter-reared monkeys recovered from the induced hyperopic errors. Conclusions The observed hyperopic shifts indicate that emmetropization does not necessarily target the focal plane that maximizes luminance contrast and that reducing potential chromatic cues can interfere with emmetropization. There was no evidence that environments dominated by long wavelengths necessarily promote myopia development. PMID:26447984

  20. Rhesus monkey brain development during late infancy and the effect of phencyclidine: a longitudinal MRI and DTI study.

    PubMed

    Liu, Cirong; Tian, Xiaoguang; Liu, Huilang; Mo, Yin; Bai, Fan; Zhao, Xudong; Ma, Yuanye; Wang, Jianhong

    2015-02-15

    Early brain development is a complex and rapid process, the disturbance of which may cause the onset of brain disorders. Based on longitudinal imaging data acquired from 6 to 16 months postnatal, we describe a systematic trajectory of monkey brain development during late infancy, and demonstrate the influence of phencyclidine (PCP) on this trajectory. Although the general developmental trajectory of the monkey brain was close to that of the human brain, the development in monkeys was faster and regionally specific. Gray matter volume began to decrease during late infancy in monkeys, much earlier than in humans in whom it occurs in adolescence. Additionally, the decrease of gray matter volume in higher-order association regions (the frontal, parietal and temporal lobes) occurred later than in regions for primary functions (the occipital lobe and cerebellum). White matter volume displayed an increasing trend in most brain regions, but not in the occipital lobe, which had a stable volume. In addition, based on diffusion tensor imaging, we found an increase in fractional anisotropy and a decrease in diffusivity, which may be associated with myelination and axonal changes in white matter tracts. Meanwhile, we tested the influence of 14-day PCP treatment on the developmental trajectories. Such treatment tended to accelerated brain maturation during late infancy, although not statistically significant. These findings provide comparative information for the understanding of primate brain maturation and neurodevelopmental disorders.

  1. Tissue-engineered rhesus monkey nerve grafts for the repair of long ulnar nerve defects: similar outcomes to autologous nerve grafts

    PubMed Central

    Jiang, Chang-qing; Hu, Jun; Xiang, Jian-ping; Zhu, Jia-kai; Liu, Xiao-lin; Luo, Peng

    2016-01-01

    Acellular nerve allografts can help preserve normal nerve structure and extracellular matrix composition. These allografts have low immunogenicity and are more readily available than autologous nerves for the repair of long-segment peripheral nerve defects. In this study, we repaired a 40-mm ulnar nerve defect in rhesus monkeys with tissue-engineered peripheral nerve, and compared the outcome with that of autograft. The graft was prepared using a chemical extract from adult rhesus monkeys and seeded with allogeneic Schwann cells. Pathomorphology, electromyogram and immunohistochemistry findings revealed the absence of palmar erosion or ulcers, and that the morphology and elasticity of the hypothenar eminence were normal 5 months postoperatively. There were no significant differences in the mean peak compound muscle action potential, the mean nerve conduction velocity, or the number of neurofilaments between the experimental and control groups. However, outcome was significantly better in the experimental group than in the blank group. These findings suggest that chemically extracted allogeneic nerve seeded with autologous Schwann cells can repair 40-mm ulnar nerve defects in the rhesus monkey. The outcomes are similar to those obtained with autologous nerve graft. PMID:28123431

  2. Identification of major urinary metabolites of nafarelin acetate, a potent agonist of luteinizing hormone-releasing hormone, in the rhesus monkey

    SciTech Connect

    Chan, R.L.; Chaplin, M.D.

    1985-09-01

    Nafarelin acetate (less than Glu-His-Trp-Ser-Tyr-3-(2-naphthyl)-D-Ala-Leu-Arg-Pro-Gly-NH2) is a potent agonistic analogue of luteinizing hormone-releasing hormone. After a single iv administration of nafarelin acetate (with UC label at C-3 of 3-(2-naphthyl)-D-Ala) to female rhesus monkeys, about 80% of the radioactivity was eliminated in urine. Five major radioactive urinary metabolites were isolated and purified by reversed phase HPLC. Four of these metabolites, identified by amino acid analysis, were short peptides: the 5-10-hexapeptide amide, the 6-10-pentapeptide amide, the 5-7-tripeptide, and the 6-7-dipeptide. The fifth metabolite, which accounted for about 15% of the radioactivity administered, was shown by NMR and mass spectrometry to be 2-naphthylacetic acid. A possible pathway of its formation is by oxidative deamination of 3-(2-napthyl)-D-Ala to give the corresponding alpha-keto acid, followed by oxidative decarboxylation of the alpha-keto acid. These five metabolites together accounted for about 70% of the radioactivity recovered in the urine of rhesus monkeys, or more than half of the radioactivity in the administered dose. Nafarelin acetate was also present in small amounts. Several of these metabolites were also present in plasma of the rhesus monkey.

  3. Drug-Containing Gelatin Treats as an Alternative to Gavage for Long-Term Oral Administration in Rhesus Monkeys (Macaca mulatta)

    PubMed Central

    Zhang, Shuang; Ye, Bin; Zeng, Li; Chen, Younan; He, Sirong; Wang, Chengshi; Li, Xinli; Zhao, Jiuming; Shi, Meimei; Wang, Li; Li, Hongxia; Cheng, Jingqiu; Wang, Wei; Lu, Yanrong

    2012-01-01

    Long-term oral administration of immunosuppressive agents to transplanted rhesus monkeys (Macaca mulatta) is one of the major challenges in such studies. To avoid the drawbacks of gavage, we tested an alternative method for oral dosing of sirolimus in rhesus monkeys by adding sirolimus, a commonly used immunosuppressant, to gelatin to create drug-containing gelatin ‘treats’ that our macaques would accept voluntarily. We evaluated the oral bioequivalence of the oral solution and drug-containing gelatin and assayed the whole-blood levels of sirolimus after long-term drug delivery. We found that time to peak concentration but not peak concentration itself or the area under the time–concentration curve differed between the 2 groups. Although the maximal concentration data did not fit the condition of bioequivalence, those for the time–concentration curves from 0 to 24 h and from 0 h to infinity did; therefore the extent of sirolimus absorption did not differ significantly between the 2 formulations. The sirolimus levels for long-term drug delivery were equivalent at 2.97 ± 1.91 ng/mL in the gelatin group and 3.13 ± 2.03 ng/mL in the solution group. The gelatin dosing technique we describe here is convenient and effective for oral administration of sirolimus in rhesus monkeys and likely can be adapted for other drugs. PMID:23294893

  4. Milk composition of captive vervet monkey (Chlorocebus pygerythrus) and rhesus macaque (Macaca mulatta) with observations on gorilla (Gorilla gorilla gorilla) and white handed gibbon (Hylobates lar).

    PubMed

    Osthoff, G; Hugo, A; de Wit, M; Nguyen, T P M; Seier, J

    2009-04-01

    The nutrient content and fatty acid composition of vervet monkey milk has been determined and is compared with rhesus macaque, and two hominoid apes, the white handed gibbon and gorilla. With 15.7+/-4.1 g protein, 33.1+/-9.4 g fat, and 85.1+/-7.5 g lactose per kg milk, vervet monkey milk does not differ from that of rhesus macaque, and is within the range of other primates. Small amounts (>1 g kg(-1)) of oligosaccharides, glucose, galactose and fucose were noted. In comparison, gorilla milk has a low fat content of 13.8 g kg(-1), but contains high levels of oligosaccharides at 7.0 g kg(-1) milk. The hominoid partner, the white handed gibbon, contains no oligosaccharides and a milk fat content similar to other hominoid species. Differences between vervet monkey and rhesus macaque milks were observed in the electrophoretic pattern of the milk proteins, mainly amongst the kappa- and gamma-caseins, which also differ from that of the hominids. The fatty acid contents of these milks differ from studies where a natural diet of leafy material was available in that a low content of alpha-linolenic acid (18:3n-3) was noted. A phylogenetic effect is observed for the content of 8:0, 10:0 fatty acids between the Cercopithecidae and Hominoidea, and a further phylogenetic effect suggested between the Hylobatidae and Hominidae.

  5. Development and validation of an LC-ESI-MS/MS method for the quantitation of hemslecin A in rhesus monkey plasma and its application in pharmacokinetics.

    PubMed

    Bai, Min; Li, Hong-Liang; He, Jian-Chang; He, Gong-Hao; Feng, En-Fu; Liu, Yue-Qiong; Shi, Pan-Pan; Xu, Gui-Li

    2014-03-01

    In this study, a new LC-ESI-MS/MS-based method was validated for the quantitation of hemslecin A in rhesus monkey plasma using otophylloside A as internal standard (IS). Hemslecin A and the IS were extracted from rhesus monkey plasma using liquid-liquid extraction as the sample clean-up procedure, and were subjected to chromatography on a Phenomenex Luna CN column (150 × 2.0 mm, 3.0 µm) with the mobile phase consisting of methanol and 0.02 mol/mL ammonium acetate (55:45, v/v) at a flow rate of 0.2 mL/min. Detection was performed on an Agilent G6410B tandem mass spectrometer by positive ion electrospray ionization in multiple reaction monitoring mode, monitoring the transitions m/z 580.5 [M + NH4 ](+)  → 503.4 and m/z 518.2 [M + NH4 ](+)  → 345.0 for hemslecin A and IS, respectively. The assay was linear over the concentration range of 0.5-200 ng/mL and was successfully applied to a pharmacokinetic study in rhesus monkeys.

  6. Treatment and risk factor analysis of hypoglycemia in diabetic rhesus monkeys.

    PubMed

    He, Sirong; Chen, Younan; Wei, Lingling; Jin, Xi; Zeng, Li; Ren, Yan; Zhang, Jie; Wang, Li; Li, Hongxia; Lu, Yanrong; Cheng, Jingqiu

    2011-02-01

    In order to anticipate and promptly treat hypoglycemia in diabetic monkeys treated with insulin or other glucose-lowering drugs, the relationships between the incidence and symptoms of hypoglycemia in these animals, and many factors involved in model development and sustainment were analyzed. Different procedures were performed on 22 monkeys for the induction of diabetes. The monkey models were evaluated by blood glucose, insulin, C-peptide levels and intravenous glucose tolerance tests. A glucose treatment program for the diabetic monkeys was administered and laboratory tests were regularly performed. A standard procedure of hypoglycemia treatment was established and the risk factors of hypoglycemia were analyzed by a logistic regression model. Furthermore, the relationships between the four methods of diabetes induction, renal function, glycemic control and hypoglycemia were studied using one-way analysis of variance and t-test. We found that the hypoglycemic conditions of diabetic monkeys were improved rapidly by our treatment. The statistical analysis suggested that the modeling methods, renal function and glycemic control were related to the incidence of hypoglycemia. In detail, the progress of diabetes, effects of glycemic control and, particularly, the severity of the hypoglycemia differed according to the induction strategy used. The models induced by partial pancreatectomy with low-dose streptozotocin were not prone to hypoglycemia and their glycemic controls were stable. However, the models induced by total pancreatectomy were more vulnerable to severe hypoglycemia and their glycemic controls were the most unstable. Moreover, the levels of blood creatinine and triglyceride increased after the development of diabetes, which was related to the occurrence of hypoglycemia. In conclusion, we suggested that total pancreatectomy and renal impairment are two important risk factors for hypoglycemia in diabetic monkeys. More attention should be paid to daily care

  7. Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9.

    PubMed

    Chen, Yongchang; Zheng, Yinghui; Kang, Yu; Yang, Weili; Niu, Yuyu; Guo, Xiangyu; Tu, Zhuchi; Si, Chenyang; Wang, Hong; Xing, Ruxiao; Pu, Xiuqiong; Yang, Shang-Hsun; Li, Shihua; Ji, Weizhi; Li, Xiao-Jiang

    2015-07-01

    CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene or cause the pathology seen in human disease. Addressing these issues is necessary if we are to generate large animal models of human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey dystrophin gene to create mutations that lead to Duchenne muscular dystrophy (DMD), a recessive X-linked form of muscular dystrophy. Examination of the relative targeting rate revealed that Crispr/Cas9 targeting could lead to mosaic mutations in up to 87% of the dystrophin alleles in monkey muscle. Moreover, CRISPR/Cas9 induced mutations in both male and female monkeys, with the markedly depleted dystrophin and muscle degeneration seen in early DMD. Our findings indicate that CRISPR/Cas9 can efficiently generate monkey models of human diseases, regardless of inheritance patterns. The presence of degenerated muscle cells in newborn Cas9-targeted monkeys suggests that therapeutic interventions at the early disease stage may be effective at alleviating the myopathy.

  8. Functional disruption of the dystrophin gene in rhesus monkey using CRISPR/Cas9

    PubMed Central

    Chen, Yongchang; Zheng, Yinghui; Kang, Yu; Yang, Weili; Niu, Yuyu; Guo, Xiangyu; Tu, Zhuchi; Si, Chenyang; Wang, Hong; Xing, Ruxiao; Pu, Xiuqiong; Yang, Shang-Hsun; Li, Shihua; Ji, Weizhi; Li, Xiao-Jiang

    2015-01-01

    CRISPR/Cas9 has been used to genetically modify genomes in a variety of species, including non-human primates. Unfortunately, this new technology does cause mosaic mutations, and we do not yet know whether such mutations can functionally disrupt the targeted gene or cause the pathology seen in human disease. Addressing these issues is necessary if we are to generate large animal models of human diseases using CRISPR/Cas9. Here we used CRISPR/Cas9 to target the monkey dystrophin gene to create mutations that lead to Duchenne muscular dystrophy (DMD), a recessive X-linked form of muscular dystrophy. Examination of the relative targeting rate revealed that Crispr/Cas9 targeting could lead to mosaic mutations in up to 87% of the dystrophin alleles in monkey muscle. Moreover, CRISPR/Cas9 induced mutations in both male and female monkeys, with the markedly depleted dystrophin and muscle degeneration seen in early DMD. Our findings indicate that CRISPR/Cas9 can efficiently generate monkey models of human diseases, regardless of inheritance patterns. The presence of degenerated muscle cells in newborn Cas9-targeted monkeys suggests that therapeutic interventions at the early disease stage may be effective at alleviating the myopathy. PMID:25859012

  9. Neonatal face-to-face interactions promote later social behaviour in infant rhesus monkeys

    PubMed Central

    Dettmer, Amanda M.; Kaburu, Stefano S. K.; Simpson, Elizabeth A.; Paukner, Annika; Sclafani, Valentina; Byers, Kristen L.; Murphy, Ashley M.; Miller, Michelle; Marquez, Neal; Miller, Grace M.; Suomi, Stephen J.; Ferrari, Pier F.

    2016-01-01

    In primates, including humans, mothers engage in face-to-face interactions with their infants, with frequencies varying both within and across species. However, the impact of this variation in face-to-face interactions on infant social development is unclear. Here we report that infant monkeys (Macaca mulatta) who engaged in more neonatal face-to-face interactions with mothers have increased social interactions at 2 and 5 months. In a controlled experiment, we show that this effect is not due to physical contact alone: monkeys randomly assigned to receive additional neonatal face-to-face interactions (mutual gaze and intermittent lip-smacking) with human caregivers display increased social interest at 2 months, compared with monkeys who received only additional handling. These studies suggest that face-to-face interactions from birth promote young primate social interest and competency. PMID:27300086

  10. Uncertain responses by humans and rhesus monkeys (Macaca mulatta) in a psychophysical same-different task

    NASA Technical Reports Server (NTRS)

    Shields, W. E.; Smith, J. D.; Washburn, D. A.; Rumbaugh, D. M. (Principal Investigator)

    1997-01-01

    The authors asked whether animals, like humans, use an uncertain response adaptively to escape indeterminate stimulus relations. Humans and monkeys were placed in a same-different task, known to be challenging for animals. Its difficulty was increased further by reducing the size of the stimulus differences, thereby making many same and different trials difficult to tell apart. Monkeys do escape selectively from these threshold trials, even while coping with 7 absolute stimulus levels concurrently. Monkeys even adjust their response strategies on short time scales according to the local task conditions. Signal-detection and optimality analyses confirm the similarity of humans' and animals' performances. Whereas associative interpretations account poorly for these results, an intuitive uncertainty construct does so easily. The authors discuss the cognitive processes that allow uncertainty's adaptive use and recommend further comparative studies of metacognition.

  11. The safety evaluation of fluvastatin, an HMG-CoA reductase inhibitor, in beagle dogs and rhesus monkeys.

    PubMed

    Hartman, H A; Myers, L A; Evans, M; Robison, R L; Engstrom, R G; Tse, F L

    1996-01-01

    Fluvastatin is a potent synthetic competitive inhibitor of beta-hydroxy-beta-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme in the biosynthetic pathway for hepatic cholesterol synthesis. The therapeutic indication is reduction of elevated total and low-density lipoprotein cholesterol levels. Results from four toxicity studies in beagle dogs and one study in rhesus monkeys following oral administration of fluvastatin are reported. In two 26-week dog studies, doses were 0, 1, 8, or 48 mg/kg/day (reduced to 36 mg/kg/day in Week 7) and 0, 6, 24, or 36 mg/kg/day (reduced to 30 mg/kg/day in Week 2). In a 2-year dog study, doses were 0, 1, 8, or 16 mg/kg/day. Dose levels in the 26-week monkey study were 0, 0.6, 12, and 48 mg/kg/day (raised to 84 mg/kg/day in Week 17 and to 108 mg/kg/day in Week 22). In these studies, evaluations included clinical and physical examinations, body weight and food consumption, electrocardiography, ophthalmoscopy, hematology and clinical chemistries, urinalysis, blood drug concentration, and macroscopic and microscopic examinations of observed lesions and representative tissues. In the 26- and 52-week dog studies and the monkey study, lenticular biochemistry, the HMG-CoA reductase activity of liver microsomes, and serum lipid concentrations were investigated. The fourth dog study was a single-dose toxicokinetic study in which 48 mg/kg [3H]-fluvastatin was monitored for up to 2 weeks. Sampling was limited to ocular tissues for enzyme analysis. Doses of > or = 24 mg/kg/day were lethal in dogs. At lethal doses, ataxia, convulsions, fecal blood, multifocal congestion and hemorrhage, isolated foci of malacia in the medulla oblongata, and liver necrosis were observed. Reduced weight gain, emesis, cataracts, elevated liver enzymes, reduced cholesterol, and gallbladder inflammation with mucosal hyperplasia occurred at > or = 8 mg/kg/day. In contrast to other HMG-CoA reductase inhibitors, fluvastatin did not cause significant

  12. Sodium Taurocholate Modifies the Bile Acid-Independent Fraction of Canalicular Bile Flow in the Rhesus Monkey

    PubMed Central

    Baker, Alfred L.; Wood, R. A. B.; Moossa, A. R.; Boyer, James L.

    1979-01-01

    Bile acid-independent secretion and the choleretic response to taurocholate were determined in rhesus monkeys fitted with indwelling silastic cannulas in the common bile ducts. Bile acids were infused intravenously in random order at 3.5, 7.0, or 10.5 μmol/min for 1.5 h each. When data were analyzed with a single regression line, bile flow increased in proportion to the level of bile acid secretion, although the y-intercepts (the conventional measurement of bile acid-independent secretion) varied widely (77.9±40.9 ml/24 h). The variation in y-intercepts was observed between animals and with repeated studies in the same animal and could not be explained by sex differences or the effects of the indwelling silastic cannulas, but seemed to be related to the order of bile acid infusion. With only two taurocholic acid infusion rates (7.0 and 3.5 μmol/min), [14C]erythritol clearance was greater per mole of secreted bile acid when the initial bile acid infusion was at the high level, but approached zero at low bile acid secretion rates, which suggests that so-called bile acid-independent canalicular flow is closely related to bile acid secretion or is small in size. The augmentation in [14C]erythritol clearance when the high infusion rate was given first was also associated with an increase in biliary clearance of [3H]inulin, which indicates that the premeability to inulin was also enhanced. Identical experiments which substituted equimolar infusions of a nonmicelle-forming bile acid (taurodehydrocholate) for taurocholate failed to demonstrate any difference in choleretic response or biliary clearance of [3H]inulin with the order of bile acid infusion. These experiments demonstrate that a micelleforming bile acid, taurocholate, can increase the permeability of the biliary system to large molecular weight solutes and simultaneously modify the y-intercept and the volume of bile secreted in response to the transported bile acid. Taurocholate may, therefore, modify its own

  13. Beta(3)-adrenoceptor agonist-induced increases in lipolysis, metabolic rate, facial flushing, and reflex tachycardia in anesthetized rhesus monkeys.

    PubMed

    Hom, G J; Forrest, M J; Bach, T J; Brady, E; Candelore, M R; Cascieri, M A; Fletcher, D J; Fisher, M H; Iliff, S A; Mathvink, R; Metzger, J; Pecore, V; Saperstein, R; Shih, T; Weber, A E; Wyvratt, M; Zafian, P; MacIntyre, D E

    2001-04-01

    The effects of two beta(3)-adrenergic receptor agonists, (R)-4-[4-(3-cyclopentylpropyl)-4,5-dihydro-5-oxo-1H-tetrazol-1-yl]-N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)ethyl]amino]ethyl]phenyl]benzenesulfonamide and (R)-N-[4-[2-[[2-hydroxy-2-(3-pyridinyl)- ethyl]amino]ethyl]phenyl]-1-(4-octylthiazol-2-yl)-5-indolinesulfonamide, on indices of metabolic and cardiovascular function were studied in anesthetized rhesus monkeys. Both compounds are potent and specific agonists at human and rhesus beta(3)-adrenergic receptors. Intravenous administration of either compound produced dose-dependent lipolysis, increase in metabolic rate, peripheral vasodilatation, and tachycardia with no effects on mean arterial pressure. The increase in heart rate in response to either compound was biphasic with an initial rapid component coincident with the evoked peripheral vasodilatation and a second more slowly developing phase contemporaneous with the evoked increase in metabolic rate. Because both compounds exhibited weak binding to and activation of rhesus beta(1)-adrenergic receptors in vitro, it was hypothesized that the increase in heart rate may be reflexogenic in origin and proximally mediated via release of endogenous norepinephrine acting at cardiac beta(1)-adrenergic receptors. This hypothesis was confirmed by determining that beta(3)-adrenergic receptor agonist-evoked tachycardia was attenuated in the presence of propranolol and in ganglion-blocked animals, under which conditions there was no reduction in the evoked vasodilatation, lipolysis, or increase in metabolic rate. It is not certain whether the beta(3)-adrenergic receptor-evoked vasodilatation is a direct effect of compounds at beta(3)-adrenergic receptors in the peripheral vasculature or is secondary to the release or generation of an endogenous vasodilator. Peripheral vasodilatation in response to beta(3)-adrenergic receptor agonist administration was not attenuated in animals administered mepyramine, indomethacin, or

  14. Elevated androgens during puberty in female rhesus monkeys lead to increased neuronal drive to the reproductive axis: a possible component of polycystic ovary syndrome

    PubMed Central

    McGee, W.K.; Bishop, C.V.; Bahar, A.; Pohl, C.R.; Chang, R.J.; Marshall, J.C.; Pau, F.K.; Stouffer, R.L.; Cameron, J.L.

    2012-01-01

    BACKGROUND Hyperandrogenemia is associated with several clinical disorders in which both reproductive dysfunction and metabolic changes may coexist [i.e. polycystic ovary syndrome (PCOS), obesity and congenital adrenal hyperplasia]. Moreover, there is growing evidence that the elevated levels of circulating androgens in obese girls may lead to an increased neuroendocrine drive to the reproductive axis, similar to that associated with PCOS. METHODS To test whether androgen exposure in the childhood and adolescent period could lead to pubertal alterations in LH secretory patterns, female rhesus monkeys received subcutaneous testosterone implants prepubertally beginning at 1 year of age, maintaining a 3.7-fold increase (P = 0.001) in circulating testosterone levels over cholesterol-implant controls (n = 6/group) into the post-pubertal period. In early adulthood, pulsatile secretion of LH was measured over 12 h during the early follicular phase of a menstrual cycle, and responsiveness of the pituitary to gonadotrophin-releasing hormone was determined. In addition, ultrasounds were performed to assess ovarian morphology and glucose tolerance testing was performed to assess insulin sensitivity. RESULTS The timing of menarche was similar between groups. Testosterone-treated animals had a significantly greater LH pulse frequency during the early follicular phase compared with controls (P = 0.039) when measured at 5 years of age. There was a larger LH response to GnRH when testosterone-treated animals were 4 years of age (P = 0.042), but not when the animals were 5 years old (P = 0.57). No differences were seen in insulin sensitivity or ovarian morphology, and the groups showed similar rates of ovulation in early adulthood. CONCLUSIONS Exposure to increased levels of androgens over the course of pubertal development appears to trigger physiological changes in the neural drive to the reproductive axis that resemble those of obese hyperandrogenemic girls in early adulthood

  15. Effects of short-term oral dosing of polychlorotrifluoroethylene (polyCTFE) on the rhesus monkey. (Reannouncement with new availability information). Final report, March 1989-March 1990

    SciTech Connect

    Jones, C.E.; Ballinger, M.B.; Seckel, C.; Vinegar, A.; Mattie, D.R.

    1991-12-31

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

  16. Selection of behavioral tasks and development of software for evaluation of Rhesus Monkey behavior during spaceflight

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.; Washburn, David A.; Richardson, W. K.

    1996-01-01

    The results of several experiments were disseminated during this semiannual period. These publications and presented papers represent investigations of the continuity in psychological processes between monkeys and humans. Thus, each serves to support the animal model of behavior and performance research.

  17. Selection of behavioral tasks and development of software for evaluation of Rhesus Monkey behavior during spaceflight

    NASA Technical Reports Server (NTRS)

    Rumbaugh, Duane M.; Washburn, David A.; Richardson, W. K.

    1995-01-01

    The results of several experiments were disseminated during this semiannual period. This publication and each of these presented papers represent investigations of the continuity in psychological processes between monkeys and humans. Thus, each serves to support the animal model of behavior and performance research.

  18. Dissociation of Active Working Memory and Passive Recognition in Rhesus Monkeys

    ERIC Educational Resources Information Center

    Basile, Benjamin M.; Hampton, Robert R.

    2013-01-01

    Active cognitive control of working memory is central in most human memory models, but behavioral evidence for such control in nonhuman primates is absent and neurophysiological evidence, while suggestive, is indirect. We present behavioral evidence that monkey memory for familiar images is under active cognitive control. Concurrent cognitive…

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

    DTIC Science & Technology

    1990-01-01

    portal cellular infiltrate involving vascular walls, connective tissue, and adjacent hepatic plates was observed in several portal triads... Lymphoplasmacytes dominated the infiltra- tion, however, macrophages and granulocytes were distributed among the lym- phoid cells. Moderate, multifocal, epicardial...primarily of lymphoplasmacytic cells. Interferon response in RVF virus-inficted monkeys 207 Table 5. Viral titers" of organs from fatally infected

  20. Evaluating the Behavioral and Physiological Safety of Human Butyrylcholinesterase in Rhesus Monkeys

    DTIC Science & Technology

    2005-10-01

    Grauer , Grunwald, Cohen, & Ashani, 1997; Wolfe et al., 1992; Wolfe, Rush, Doctor, Koplovitz, & Jones, 1987). A clear advantage of using this strategy...Raveh, L., Grauer , E., Grunwald, J., Cohen, E., & Ashani, Y. (1997). The stoichiometry of protection against soman and VX toxicity in monkeys

  1. Effects of chair restraint on the strength of the tibia in rhesus monkeys

    NASA Technical Reports Server (NTRS)

    Hutchinson, T. M.; Bakulin, A. V.; Rakhmanov, A. S.; Martin, R. B.; Steele, C. R.; Arnaud, S. B.

    2001-01-01

    To determine the effects of the relative inactivity and unloading on the strength of the tibias of monkeys, Macaca mulatta, we used a non-invasive test to measure bending stiffness, or EI (Nm2), a mechanical property. The technique was validated by comparisons of in vivo measurements with standard measures of EI in the same bones post-mortem (r2 = 0.95, P < 0.0001). Inter-test precision was 4.28+/-1.4%. Normative data in 24 monkeys, 3.0+/-0.7 years and 3.6+/-0.6 kg, revealed EI to be 16% higher in the right than left tibia (4.4+/-1.6 vs. 3.7+/-1.6 Nm2, P < 0.05). Five monkeys, restrained in chairs for 14 days, showed decreases in EI. There were no changes in EI in two chaired monkeys that lost weight during a 2-week space flight. The factors that account for both the decreases in bone mechanical properties after chair restraint at 1 g and lack of change after microgravity remain to be identified. Metabolic factors associated with body weight changes are suggested by our results.

  2. Dissociation of visual localization and visual detection in rhesus monkeys (Macaca mulatta).

    PubMed

    Andersen, Lau M; Basile, Benjamin M; Hampton, Robert R

    2014-05-01

    Conscious and unconscious cognitive processes contribute independently to human behavior and can be dissociated. For example, humans report failing to see objects clearly in the periphery while simultaneously being able to grasp those objects accurately (Milner in Proc R Soc B Biol Sci 279:2289-2298, 2012). Knowing whether similar dissociations are present in nonverbal species is critical to our understanding of comparative psychology and the evolution of brains. However, such dissociations are difficult to detect in nonhumans because verbal reports of experience are the main way we discriminate putative conscious from unconscious processing. We trained monkeys in a localization task in which they responded to the location where a target appeared, and a matched detection task in which they reported the presence or absence of the same target. We used masking to manipulate the visibility of targets. Accuracy was high in both tasks when stimuli were unmasked and was attenuated by visual masking. At the strongest level of masking, performance in the detection task was at chance, while localization remained significantly above chance. Critically, errors in the detection task were predominantly misses, indicating that the monkeys' behavior remained under stimulus control, but that the monkeys did not detect the target despite above-chance localization. While these results cannot establish the existence of phenomenal vision in monkeys, the dissociation of visually guided action from detection parallels the dissociation of conscious and unconscious vision seen in humans.

  3. NATURE OF NON-PARALYTIC AND TRANSITORY PARALYTIC POLIOMYELITIS IN RHESUS MONKEYS INOCULATED WITH HUMAN VIRUS

    PubMed Central

    Sabin, Albert B.; Ward, Robert

    1941-01-01

    1. The occurrence of non-paralytic poliomyelitis in monkeys inoculated with human or first passage virus was proved by histological examination of the nervous system and by isolation of the virus. 2. The non-paralytic infection was almost invariably associated with the destruction of an appreciable number of nerve cells in the spinal cord, and failure of the process to progress seemed to depend upon an equilibrium between the host and the virus, in which the latter occasionally persisted in an active state since it could produce the typical paralytic disease on passage to other monkeys. 3. While there were no reliable clinical or laboratory criteria, the diagnosis of non-paralytic poliomyelitis was made when the following changes were found in the spinal cord: (a) outfall of neurons confirmed by the presence of the reaction of degeneration in the nerve roots, and (b) foci of glial infiltration and perivascular cuffing in the gray matter. 4. Anterior horn cells showing diffuse chromatolysis and acidophilic, intranuclear inclusions were present 2 days after disappearance of paralysis of short duration, and nerve cells with marginated Nissl substance and eccentric nuclei were found side by side with obviously older lesions in monkeys with non-paralytic poliomyelitis. These cytologic changes were not present in monkeys sacrificed in still later stages of the disease. 5. The transitory character of the paralysis in some monkeys may depend in part on the fact that apparently normal function can be carried on with less than the normal number of nerve cells and in part on the probable, but not proved, possibility that not all nerve cells attacked by poliomyelitis virus are irreversibly damaged. PMID:19871110

  4. Evaluation of the Reinforcing Effect of Quetiapine, Alone and in Combination with Cocaine, in Rhesus Monkeys.

    PubMed

    Brutcher, Robert E; Nader, Susan H; Nader, Michael A

    2016-02-01

    There are several case reports of nonmedicinal quetiapine abuse, yet there are very limited preclinical studies investigating quetiapine self-administration. The goal of this study was to investigate the reinforcing effects of quetiapine alone and in combination with intravenous cocaine in monkeys. In experiment 1, cocaine-experienced female monkeys (N = 4) responded under a fixed-ratio (FR) 30 schedule of food reinforcement (1.0-g banana-flavored pellets), and when responding was stable, quetiapine (0.003-0.1 mg/kg per injection) or saline was substituted for a minimum of five sessions; there was a return to food-maintained responding between doses. Next, monkeys were treated with quetiapine (25 mg, by mouth, twice a day) for approximately 30 days, and then the quetiapine self-administration dose-response curve was redetermined. In experiment 2, male monkeys (N = 6) self-administered cocaine under a concurrent FR schedule with food reinforcement (three food pellets) as the alternative to cocaine (0.003-0.3 mg/kg per injection) presentation. Once choice responding was stable, the effects of adding quetiapine (0.03 or 0.1 mg/kg per injection) to the cocaine solution were examined. In experiment 1, quetiapine did not function as a reinforcer, and chronic quetiapine treatment did not alter these effects. In experiment 2, cocaine choice increased in a dose-dependent fashion. The addition of quetiapine to cocaine resulted in increases in low-dose cocaine choice and number of cocaine injections in four monkeys, while not affecting high-dose cocaine preference. Thus, although quetiapine alone does not have abuse potential, there was evidence of enhancement of the reinforcing potency of cocaine. These results suggest that the use of quetiapine in cocaine-addicted patients should be monitored.

  5. NATURE OF NON-PARALYTIC AND TRANSITORY PARALYTIC POLIOMYELITIS IN RHESUS MONKEYS INOCULATED WITH HUMAN VIRUS.

    PubMed

    Sabin, A B; Ward, R

    1941-05-31

    1. The occurrence of non-paralytic poliomyelitis in monkeys inoculated with human or first passage virus was proved by histological examination of the nervous system and by isolation of the virus. 2. The non-paralytic infection was almost invariably associated with the destruction of an appreciable number of nerve cells in the spinal cord, and failure of the process to progress seemed to depend upon an equilibrium between the host and the virus, in which the latter occasionally persisted in an active state since it could produce the typical paralytic disease on passage to other monkeys. 3. While there were no reliable clinical or laboratory criteria, the diagnosis of non-paralytic poliomyelitis was made when the following changes were found in the spinal cord: (a) outfall of neurons confirmed by the presence of the reaction of degeneration in the nerve roots, and (b) foci of glial infiltration and perivascular cuffing in the gray matter. 4. Anterior horn cells showing diffuse chromatolysis and acidophilic, intranuclear inclusions were present 2 days after disappearance of paralysis of short duration, and nerve cells with marginated Nissl substance and eccentric nuclei were found side by side with obviously older lesions in monkeys with non-paralytic poliomyelitis. These cytologic changes were not present in monkeys sacrificed in still later stages of the disease. 5. The transitory character of the paralysis in some monkeys may depend in part on the fact that apparently normal function can be carried on with less than the normal number of nerve cells and in part on the probable, but not proved, possibility that not all nerve cells attacked by poliomyelitis virus are irreversibly damaged.

  6. Maternal antibodies from mothers of children with autism alter brain growth and social behavior development in the rhesus monkey.

    PubMed

    Bauman, M D; Iosif, A-M; Ashwood, P; Braunschweig, D; Lee, A; Schumann, C M; Van de Water, J; Amaral, D G

    2013-07-09

    Antibodies directed against fetal brain proteins of 37 and 73 kDa molecular weight are found in approximately 12% of mothers who have children with autism spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised the possibility that these immunoglobulin G (IgG) class antibodies cross the placenta during pregnancy and impact brain development, leading to one form of ASD. We evaluated the pathogenic potential of these antibodies by using a nonhuman primate model. IgG was isolated from mothers of children with ASD (IgG-ASD) and of typically developing children (IgG-CON). The purified IgG was administered to two groups of female rhesus monkeys (IgG-ASD; n=8 and IgG-CON; n=8) during the first and second trimesters of pregnancy. Another control group of pregnant monkeys (n=8) was untreated. Brain and behavioral development of the offspring were assessed for 2 years. Behavioral differences were first detected when the macaque mothers responded to their IgG-ASD offspring with heightened protectiveness during early development. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently approaching familiar peers. The increased approach was not reciprocated and did not lead to sustained social interactions. Even more striking, IgG-ASD offspring displayed inappropriate approach behavior to unfamiliar peers, clearly deviating from normal macaque social behavior. Longitudinal magnetic resonance imaging analyses revealed that male IgG-ASD offspring had enlarged brain volume compared with controls. White matter volume increases appeared to be driving the brain differences in the IgG-ASD offspring and these differences were most pronounced in the frontal lobes.

  7. Toxicity and hemodynamic effects after single dose administration of MalPEG-hemoglobin (MP4) in rhesus monkeys.

    PubMed

    Young, Mark A; Malavalli, Ashok; Winslow, Nancy; Vandegriff, Kim D; Winslow, Robert M

    2007-06-01

    Maleimide-polyethylene glycol-modified (MalPEG) hemoglobin, 4.3 g/dL (MP4; Hemospan), is a hemoglobin-based oxygen carrier consisting of human hemoglobin (Hb) modified with maleimide polyethylene glycol. This study evaluates the potential toxicity and hemodynamic actions of a single dose of MP4 administered by exchange transfusion to rhesus monkeys. Monkeys were administered MP4 (21 mL/kg, or approximately 30% of estimated blood volume) or an equivalent volume of lactated Ringer's solution (LR). In the toxicity study, blood samples were obtained predose and 3, 7, and 13 days after dosing for clinical chemistry and hematology. Animals were euthanized for complete necropsy and histopathology on day 3 or day 13. A separate group of animals was used for evaluation of arterial pressure, core temperature, and electrocardiogram, by telemetry, for 7 days after dosing with MP4. The results demonstrate no significant toxicity, with only modest, transient elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) on day 3. Mild anemia caused by hemodilution was observed at each time point in both groups, but to a slightly greater degree in the MP4-treated animals. Histologic observations included foamy or vacuolated macrophages in the spleen and marrow of the sternum, rib, and femur, representing the accumulation of test article or a metabolite. In the telemetry study, no changes occurred in arterial pressure, heart rate, or electrocardiogram attributable to administration of MP4 at any time for 7 days after administration. These results demonstrate that MP4 is safe and is without hemodynamic effects when administered as an exchange transfusion of 30% of estimated blood volume.

  8. Effects of phendimetrazine treatment on cocaine vs food choice and extended-access cocaine consumption in rhesus monkeys.

    PubMed

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

    2013-12-01

    There is currently no Food and Drug Administration-approved pharmacotherapy for cocaine addiction. Monoamine releasers such as d-amphetamine constitute one class of candidate medications, but clinical use and acceptance are hindered by their own high-abuse liability. Phendimetrazine (PDM) is a schedule III anorectic agent that functions as both a low-potency monoamine-uptake inhibitor and as a prodrug for the monoamine-releaser phenmetrazine (PM), and it may serve as a clinically available, effective, and safer alternative to d-amphetamine. This study determined efficacy of chronic PDM to reduce cocaine self-administration by rhesus monkeys (N=4) using a novel procedure that featured both daily assessments of cocaine vs food choice (to assess medication efficacy to reallocate behavior away from cocaine choice and toward choice of an alternative reinforcer) and 20 h/day cocaine access (to allow high-cocaine intake). Continuous 21-day treatment with ramping PDM doses (days 1-7: 0.32 mg/kg/h; days 8-21: 1.0 mg/kg/h) reduced cocaine choices, increased food choices, and nearly eliminated extended-access cocaine self-administration without affecting body weight. There was a trend for plasma PDM and PM levels to correlate with efficacy to decrease cocaine choice such that the monkey with the highest plasma PDM and PM levels also demonstrated the greatest reductions in cocaine choice. These results support further consideration of PDM as a candidate anti-cocaine addiction pharmacotherapy. Moreover, PDM may represent a novel pharmacotherapeutic approach for cocaine addiction because it may simultaneously function as both a monoamine-uptake inhibitor (via the parent drug PDM) and as a monoamine releaser (via the active metabolite PM).

  9. Integrated Role of Bifidobacterium animalis subsp. lactis Supplementation in Gut Microbiota, Immunity, and Metabolism of Infant Rhesus Monkeys

    PubMed Central

    He, Xuan; Dekker, James W.; Haggarty, Neill W.; Lönnerdal, Bo

    2016-01-01

    ABSTRACT To investigate the impact of probiotic supplementation of infant formula on immune parameters, intestinal microbiota, and metabolism, five individually housed infant rhesus monkeys exclusively fed standard infant formula supplemented with probiotics (Bifidobacterium animalis subsp. lactis HN019) from birth until 3 months of age were compared with five standard formula-fed and five breast-fed monkeys. Anthropometric measurements, serum insulin, immune parameters, fecal microbiota, and metabolic profiles of serum, urine, and feces were evaluated. Consumption of B. lactis-supplemented formula reduced microbial diversity, restructured the fecal microbial community, and altered the fecal metabolome at the last two time points, in addition to increasing short-chain fatty acids in serum and urine. Circulating CCL22 was lower and threonine, branched-chain amino acids, urea, and allantoin, as well as dimethylglycine in serum and urine, were increased in the group supplemented with B. lactis compared with the standard formula-fed group. These results support a role of probiotics as effectors of gut microbial activity regulating amino acid utilization and nitrogen cycling. Future risk-benefit analyses are still needed to consolidate the existing knowledge on the long-term consequences of probiotic administration during infancy. IMPORTANCE Probiotics are becoming increasingly popular due to their perceived effects on health, despite a lack of mechanistic information on how they impart these benefits. Infant formula and complementary foods are common targets for supplementation with probiotics. However, different probiotic strains have different properties, and there is a lack of data on long-term health effects on the consumer. Given the increasing interest in supplementation with probiotics and the fact that the gastrointestinal tracts of infants are still immature, we sought to determine whether consumption of infant formula containing the probiotic

  10. Effect of delay on self-administration of remifentanil under a drug versus drug choice procedure in rhesus monkeys.

    PubMed

    Maguire, David R; Gerak, Lisa R; France, Charles P

    2013-12-01

    Drug abuse can be conceptualized as excessive choice of drug over other reinforcers, and factors that affect drug taking can be examined experimentally using choice procedures. This study examined the impact of reinforcer delay on self-administration of the μ-opioid receptor agonist remifentanil in rhesus monkeys (n = 4) lever pressing under a concurrent fixed-ratio 30 schedule. Responding on either lever delivered an intravenous infusion of either remifentanil or saline. Dose-effect curves were first determined when responding on one lever delivered remifentanil and responding on a second lever delivered saline. Monkeys then chose between two doses of remifentanil, and delay to delivery of the large dose was varied systematically. Responding for remifentanil (0.01-1.0 µg/kg/infusion) increased dose-dependently when the alternative was saline or a dose of remifentanil. Delaying delivery of the large dose of remifentanil by 30, 60, 120, or 240 seconds increased responding for smaller, immediately available doses (0.01-0.1 µg/kg/infusion) and, in some cases, increased responding for doses of remifentanil that did not maintain responding when the alternative was saline. These data demonstrate that delaying the delivery of an opioid receptor agonist can significantly affect its reinforcing effectiveness. The imposition of a delay reduces the effectiveness of large doses of drug to maintain responding and increases the effectiveness of immediately available commodities, including smaller doses of drug. Increased reinforcing effectiveness of smaller doses of drug in the context of other delayed reinforcers might contribute to the development and maintenance of opioid abuse.

  11. Integrated Role of Bifidobacterium animalis subsp. lactis Supplementation in Gut Microbiota, Immunity, and Metabolism of Infant Rhesus Monkeys.

    PubMed

    He, Xuan; Slupsky, Carolyn M; Dekker, James W; Haggarty, Neill W; Lönnerdal, Bo

    2016-01-01

    To investigate the impact of probiotic supplementation of infant formula on immune parameters, intestinal microbiota, and metabolism, five individually housed infant rhesus monkeys exclusively fed standard infant formula supplemented with probiotics (Bifidobacterium animalis subsp. lactis HN019) from birth until 3 months of age were compared with five standard formula-fed and five breast-fed monkeys. Anthropometric measurements, serum insulin, immune parameters, fecal microbiota, and metabolic profiles of serum, urine, and feces were evaluated. Consumption of B. lactis-supplemented formula reduced microbial diversity, restructured the fecal microbial community, and altered the fecal metabolome at the last two time points, in addition to increasing short-chain fatty acids in serum and urine. Circulating CCL22 was lower and threonine, branched-chain amino acids, urea, and allantoin, as well as dimethylglycine in serum and urine, were increased in the group supplemented with B. lactis compared with the standard formula-fed group. These results support a role of probiotics as effectors of gut microbial activity regulating amino acid utilization and nitrogen cycling. Future risk-benefit analyses are still needed to consolidate the existing knowledge on the long-term consequences of probiotic administration during infancy. IMPORTANCE Probiotics are becoming increasingly popular due to their perceived effects on health, despite a lack of mechanistic information on how they impart these benefits. Infant formula and complementary foods are common targets for supplementation with probiotics. However, different probiotic strains have different properties, and there is a lack of data on long-term health effects on the consumer. Given the increasing interest in supplementation with probiotics and the fact that the gastrointestinal tracts of infants are still immature, we sought to determine whether consumption of infant formula containing the probiotic Bifidobacterium

  12. Acute respiratory bronchiolitis: an ultrastructural and autoradiographic study of epithelial cell injury and renewal in rhesus monkeys exposed to ozone.

    PubMed Central

    Castleman, W. L.; Dungworth, D. L.; Schwartz, L. W.; Tyler, W. S.

    1980-01-01

    The pathogenesis of acute respiratory bronchiolitis was examined in rhesus monkeys exposed to 0.8 ppm ozone fpr 4--50 hours. Epithelial injury and renewal was qualitatively and quantitatively characterized by correlated techniques of scanning and transmission electron microscopy as well as by light-microscopic autoradiography following labeling with tritiated thymidine. Extensive degeneration and necrosis of Type 1 epithelial cells occurred on the respiratory bronchiolar wall during the initial 4--12 hours of exposure. Increased numbers of labeled epithelial cells were present in this region after 18 hours of exposure, and the highest labeling index (18% was measured after 50 hours of exposure. Most (67--80%) of the labeled cells and all the mitotic epithelial cells (22) observed ultrastructurally were cuboidal bronchiolar epithelial cells. Of the labeled epithelial cells, 20--33% were Type 2 epithelial cells. After 50 hours of exposure the respiratory bronchiolar epithelium was hyperplastic. The predominant inflammatory cell in respiratory bronchiolar exudate was the alveolar macrophage. Monkeys that were exposed for 50 hours and allowed to recover in unozonized air for 7 days had incomplete resolution of respiratory bronchiolar epithelial hyperplasia. The results indicate that Type 1 epithelial cells lining respiratory bronchioles are the cell type most sensitive to injury and that both cuboidal bronchiolar epithelial cells and Type 2 epithelial cells function as stem cells in epithelial renewal. Images Figure 16 Figure 17 Figure 18 Figure 19 Figure 20 Figure 21 Figure 22 Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 23 Figure 24 Figure 25 Figure 9 Figure 10 Figure 26 Figure 27 Figure 11 Figure 12 Figure 13 Figure 14 Figure 15 PMID:6767409

  13. The relation of developmental changes in brain serotonin transporter (5HTT) and 5HT1A receptor binding to emotional behavior in female rhesus monkeys: effects of social status and 5HTT genotype.

    PubMed

    Embree, M; Michopoulos, V; Votaw, J R; Voll, R J; Mun, J; Stehouwer, J S; Goodman, M M; Wilson, M E; Sánchez, M M

    2013-01-03

    The goal of the present study was to examine how social subordination stress and 5HTT polymorphisms affect the development of brain serotonin (5HT) systems during the pubertal transition in female rhesus monkeys. We also examined associations with developmental changes in emotional reactivity in response to a standardized behavioral test, the Human Intruder (HI). Our findings provide the first longitudinal evidence of developmental increases in 5HT1A receptor and 5HTT binding in the brain of female primates from pre- to peripuberty. The increase in 5HT1A BP(ND) in these socially housed female rhesus monkeys is a robust finding, occurring across all groups, regardless of social status or 5HTT genotype, and occurring in the left and right hemispheres of all prefrontal regions studied, as well as the amygdala, hippocampus, hypothalamus, and raphe nuclei. 5HTT BP(ND) also showed an increase with age in raphe, anterior cingulate cortex, and dorsolateral prefrontal cortex. These changes in brain 5HT systems take place as females establish more adult-like patterns of social behavior, as well as during the HI paradigm. Indeed, the main developmental changes in behavior during the HI (increase in freezing and decrease in submission/appeasement) were related to neurodevelopmental increases in 5HT1A receptors and 5HTT, because the associations between these behaviors and 5HT endpoints emerge at peripuberty. We detected an effect of social status on 5HT1A BP(ND) in the hypothalamus and on 5HTT BP(ND) in the orbitofrontal cortex, with subordinates showing higher BP(ND) than dominants in both cases during the pubertal transition. No main effects of 5HTT genotype were observed for 5HT1A or 5HTT BP(ND). Our findings indicate that adolescence in female rhesus monkeys is a period of central 5HT reorganization, partly influenced by exposure to the social stress of subordination, that likely functions to integrate adrenal and gonadal systems and shape the behavioral response to

  14. Dengue Type Four Viruses with E-Glu345Lys Adaptive Mutation from MRC-5 Cells Induce Low Viremia but Elicit Potent Neutralizing Antibodies in Rhesus Monkeys

    PubMed Central

    Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development. PMID:24959738

  15. Dengue type four viruses with E-Glu345Lys adaptive mutation from MRC-5 cells induce low viremia but elicit potent neutralizing antibodies in rhesus monkeys.

    PubMed

    Lin, Hsiao-Han; Lee, Hsiang-Chi; Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development.

  16. Challenges in oral administration of metronidazole dissolved in drinking water to rhesus monkeys (Macaca mulatta).

    PubMed

    Labberton, Linda; Bakker, Jaco; Klomp, Rianne; Langermans, Jan A M; van Geijlswijk, Ingeborg M

    2013-06-01

    Intestinal pathogens such as Entamoeba spp. and Giardia spp. protozoans are not uncommon among rhesus macaques (Macaca mulatta) in research facilities. These infections affect the health of the macaques, potentially causing severe diarrhea, and also pose a risk of zoonotic transmission to human caretakers. Infections must therefore be treated, but no standard treatment for intestinal protozoans in macaques has been developed. Metronidazole is commonly used to treat infections with Giardia spp. and Entamoeba spp. in veterinary medicine, but evidence-based information on effectiveness and dosages for nonhuman primates is lacking, and administration of drugs to nonhuman primates is challenging. The authors designed a study to determine whether oral administration of metronidazole dissolved in drinking water would be successful in rhesus macaques. They monitored daily fluid intake of macaques given water with or without metronidazole and with or without flavored syrup. Metronidazole addition, with or without flavored syrup, resulted in a decrease in fluid intake. Although it was possible to administer metronidazole in drinking water to some macaques, the authors conclude that this strategy is not a practical clinical method because of variation in the amount of water and metronidazole ingested by the macaques.

  17. Cognition in aged rhesus monkeys: effect of DHEA and correlation with steroidogenic gene expression.

    PubMed

    Sorwell, K G; Renner, L; Weiss, A R; Neuringer, M; Kohama, S G; Urbanski, H F

    2017-03-01

    Estradiol supplementation has been shown to enhance cognitive performance in old ovariectomized rhesus macaques (Macaca mulatta). To determine if similar benefits could be achieved in perimenopausal animals using alternative hormonal supplements, we administered dehydroepiandrosterone (DHEA) to old ovary-intact female rhesus macaques for ∼2.5 months. Using computerized touch screen memory tasks, including delayed response (DR) and delayed matching-to-sample (DMS), we observed improved performance with time in all of the animals but failed to detect a significant effect of DHEA. On the other hand, gene expression profiling disclosed a significant correlation between cognitive performance and the expression of several steroidogenic and steroid-responsive genes. The DR performance was positively correlated with hippocampal expression of AKR1C3 and STAR and negatively correlated with the expression of SDRD5A1. A positive correlation was also found between DMS performance and prefrontal cortical expression of AKR1C3 and a negative correlation with STAR, as well as a negative correlation with the hippocampal expression of HSD11B1 and NR3C1. Taken together, the results suggest that steroidogenic gene regulation within the brain may help to maintain cognitive function during the perimenopausal transition period, despite a decline in sex-steroid levels in the circulation.

  18. Monochromatic ocular wave aberrations in young monkeys

    PubMed Central

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

    2006-01-01

    High-order monochromatic aberrations could potentially influence vision-dependent refractive development in a variety of ways. As a first step in understanding the effects of wave aberration on refractive development, we characterized the maturational changes that take place in the high-order aberrations of infant rhesus monkey eyes. Specifically, we compared the monochromatic wave aberrations of infant and adolescent animals and measured the longitudinal changes in the high-order aberrations of infant monkeys during the early period when emmetropization takes place. Our main findings were that (1) adolescent monkey eyes have excellent optical quality, exhibiting total RMS errors that were slightly better than those for adult human eyes that have the same numerical aperture and (2) shortly after birth, infant rhesus monkeys exhibited relatively larger magnitudes of high-order aberrations predominately spherical aberration, coma, and trefoil, which decreased rapidly to assume adolescent values by about 200 days of age. The results demonstrate that rhesus monkey eyes are a good model for studying the contribution of individual ocular components to the eye’s overall aberration structure, the mechanisms responsible for the improvements in optical quality that occur during early ocular development, and the effects of high-order aberrations on ocular growth and emmetropization. PMID:16750549

  19. Kisspeptin-10 Modulates the Proliferation and Differentiation of the Rhesus Monkey Derived Stem Cell Line: R366.4

    PubMed Central

    Huma, Tanzeel; Wang, Zhengbo; Rizak, Joshua; Ahmad, Fiaz; Shahab, Muhammad; Ma, YuanYe; Yang, Shangchuan; Hu, Xintian

    2013-01-01

    The rhesus monkey embryonic stem cell line R366.4 has been identified to differentiate into a number of cell types. However, it has not been well characterized for its response to drugs affecting reproductive endocrinology. Kisspeptins (KPs) are ligands for the GPR-54, which is known to modulate reproductive function. The current study was designed to determine the effect of the KP-10 peptide on R366.4 cells and to investigate the role of KP-GPR54 in the cell proliferation process. Four different doses (0.1, 1, 10, and 100 nM) of KP-10 and control were selected to evaluate cell growth parameters and cellular morphological changes over a 72 hr period. The cells were treated with kisspeptin-10 during the early rosette stage. Proliferation rates, analyzed by flow cytometry and cell count methods, were found to be decreased after treatment. Moreover, the number of rosettes was found to decrease following KP-10 treatments. Morphological changes consisting of neuronal projections were also witnessed. This suggested that KP-10 had an antiproliferative effect on R366.4 cells leading to a differentiation state and morphological changes consistent with neuronal stem cell development. The R366.4 stem cell line differentiates based on kisspeptin signaling and may be used to investigate reproductive cell endocrinology in vitro. PMID:24381507

  20. Fetal gene transfer using lentiviral vectors and the potential for germ cell transduction in rhesus monkeys (Macaca mulatta).

    PubMed

    Lee, C Chang I; Jimenez, Daniel F; Kohn, Donald B; Tarantal, Alice F

    2005-04-01

    Genetic modification of germ cells in somatic gene therapy protocols is a concern, particularly with fetal approaches. This study focused on the potential for germ cell gene transfer post-fetal gene delivery using a human immunodeficiency virus type 1 (HIV-1)-derived lentiviral vector pseudotyped with the vesicular stomatitis virus-glycoprotein (VSV-G). Rhesus monkey fetuses (n = 47) were administered vector supernatant (10(7) infectious particles per fetus) via the intraperitoneal (IP), intrapulmonary (Ipu), or intracardiac routes (Ica) under ultrasound guidance. Tissue harvests were performed near term or 3 months postnatal age, and genomic DNA obtained to analyze for vector sequences from collected sections of gonads and gonadal cells obtained by laser capture microdissection (germ cells, stroma, epithelium). Results indicated no evidence of germ cell gene transfer in fetuses or infants with Ipu or Ica routes of administration. However, evidence of the transgene (1.33 +/- 0.78 enhanced green fluorescent protein [EGFP] copies per copy epsilon-globin) was found in females, but not males, when using the IP administration approach (p < 0.05). The highest EGFP copies were detected on the surface epithelium (p < 0.05). The results of these studies suggest that the HIV-1-derived lentiviral vector pseudotyped with VSV-G may transduce a subpopulation of gonadal cells in female fetuses with IP administration, whereas no evidence of gene transfer was shown to occur in males or with organ-targeting approaches.

  1. The effects of K-111, a new insulin-sensitizer, on metabolic syndrome in obese prediabetic rhesus monkeys.

    PubMed

    Bodkin, N L; Pill, J; Meyer, K; Hansen, B C

    2003-10-01

    K-111, formerly BM 17.0744, (2,2-dichloro-12-(4-chlorophenyl)-dodecanoic acid) is a new insulin-sensitizer with peroxisome proliferator-activated receptor (PPAR) alpha activity but without PPAR gamma activity. We determined the efficacy of K-111 in non-human primates in increasing insulin-stimulated glucose uptake and improving metabolic syndrome, assessing the general health-related effects. Six adult male obese normoglycemic prediabetic and insulin-resistant rhesus monkeys were studied on vehicle and following K-111 treatment (four-week chronic dosing each of 3 doses: 1, 3, and 10 mg/kg/d) with assessment of changes in substrate, hormone, and blood pressure measurements and alterations in insulin sensitivity using the euglycemic, hyperinsulinemic clamp technique. K-111 led to significantly decreased body weight and improved hyperinsulinemia, insulin sensitivity, hypertriglyceridemia, and HDL-cholesterol levels without adipogenesis or significant effects on fasting glucose, 24-hour urine glucose excretion, systolic or diastolic blood pressure, plasma fibrinogen, total cholesterol, or chemistry and hematology profile. These benefits are similar to the health-improving effects of calorie restriction, providing preliminary evidence that K-111 has excellent potential as a calorie-restriction mimetic agent. These results indicate the necessity of future study of K-111 for metabolic syndrome in humans, and suggest potential in reducing the risks of diabetes and cardiovascular disease.

  2. Stability of Parental Care across Siblings from Undisturbed and Challenged Pregnancies: Intrinsic Maternal Dispositions of Female Rhesus Monkeys

    PubMed Central

    Shirtcliff, Elizabeth A.; Phan, Jenny M.; Lubach, Gabriele R.; Crispen, Heather R.; Coe, Christopher L.

    2014-01-01

    The concept of fetal programming is based on the idea that the developmental trajectory of infants is adjusted in response to in utero conditions. In species with extended parental care, these prenatally-derived tendencies are further substantiated by behavioral attributes of the mother during the postnatal period. We investigated the stability of maternal behavioral interactions with infant monkeys, and carefully varied prenatal conditions across siblings reared by the same mother. We hypothesized that effects of prenatal disturbance and the infant’s susceptibility would be differentially affected by maternal attributes. Hierarchical Linear Modeling was employed to analyze observational data on 121 rhesus macaques reared by a total of 35 multiparous mothers. A portion of the variance in 5 dyadic behaviors was statistically driven by the infant (or was unique to a particular mother-infant pair), but stable maternal propensities and a consistent style of care across siblings also substantially influenced behavioral interactions. Moreover, the magnitude and direction of the prenatal effects were contingent on a female’s intrinsic dispositions. When mothers typically exhibited high levels of a corresponding behavior, responsiveness to infants was enhanced as a consequence of prenatal disturbance. The opposite was true for less expressive females. Challenges to the wellbeing of pregnancy thus served to accentuate maternal predispositions and served to magnify the range of variation in mother-infant behavior across the whole population. PMID:23477534

  3. Application of three-dimensional culture systems to study mammalian spermatogenesis, with an emphasis on the rhesus monkey (Macaca mulatta).

    PubMed

    Huleihel, Mahmoud; Nourashrafeddin, Seyedmehdi; Plant, Tony M

    2015-01-01

    In vitro culture of spermatogonial stem cells (SSCs) has generally been performed using two-dimensional (2D) culture systems; however, such cultures have not led to the development of complete spermatogenesis. It seems that 2D systems do not replicate optimal conditions of the seminiferous tubules (including those generated by the SSC niche) and necessary for spermatogenesis. Recently, one of our laboratories has been able to induce proliferation and differentiation of mouse testicular germ cells to meiotic and postmeiotic stages including generation of sperm in a 3D soft agar culture system (SACS) and a 3D methylcellulose culture system (MCS). It was suggested that SACS and MCS form a special 3D microenvironment that mimics germ cell niche formation in the seminiferous tubules, and thus permits mouse spermatogenesis in vitro. In this review, we (1) provide a brief overview of the differences in spermatogenesis in rodents and primates, (2) summarize data related to attempts to generate sperm in vitro, (3) report for the first time formation of colonies/clusters of cells and differentiation of meiotic (expression of CREM-1) and postmeiotic (expression of acrosin) germ cells from undifferentiated spermatogonia isolated from the testis of prepubertal rhesus monkeys and cultured in SACS and MCS, and (4) indicate research needed to optimize 3D systems for in vitro primate spermatogenesis and for possible future application to man.

  4. Effects of the nicotinic acetylcholine receptor antagonist mecamylamine on the discriminative stimulus effects of cocaine in male rhesus monkeys.

    PubMed

    Banks, Matthew L

    2014-06-01

    Preclinical drug discrimination procedures have been useful in understanding the pharmacological mechanisms of the subjective-like effects of abused drugs. Converging lines of evidence from neurochemical and behavioral studies implicate a potential role of nicotinic acetylcholine (nACh) receptors in the abuse-related effects of cocaine. The aim of the present study was to determine the effects of the nACh receptor antagonist mecamylamine on the discriminative stimulus effects of cocaine in nonhuman primates. The effects of mecamylamine on the cocaine-like discriminative stimulus effects of nicotine were also examined. Male rhesus monkeys (n = 5) were trained to discriminate 0.32 mg/kg, IM cocaine from saline in a 2-key, food-reinforced discrimination procedure. Initially, potency and time course of cocaine-like discriminative stimulus effects were determined for nicotine and mecamylamine alone. Test sessions were then conducted examining the effects of mecamylamine on cocaine or the cocaine-like discriminative stimulus effects of nicotine. Curiously, mecamylamine produced partial cocaine-like discriminative stimulus effects. Mecamylamine did not significantly alter the discriminative stimulus effects of cocaine up to doses that significantly decreased rates of operant responding. Mecamylamine and nicotine combinations were not different than saline. These results confirm previous nonhuman primate studies of partial substitution with nicotine and extend these findings with mecamylamine. Furthermore, these results extend previous results in rats suggesting cocaine may have nACh receptor antagonist properties.

  5. Overlapping and nonoverlapping cortical projections to cortex of the superior temporal sulcus in the rhesus monkey: double anterograde tracer studies.

    PubMed

    Seltzer, B; Cola, M G; Gutierrez, C; Massee, M; Weldon, C; Cusick, C G

    1996-06-24

    To examine how fibers from functionally distinct cortical zones interrelate within their target areas of the superior temporal sulcus (STS) in the rhesus monkey, separate anterograde tracers were injected in two different regions of the same hemisphere known to project to the STS. Paired injections were placed in dorsal prearcuate cortex and the caudal inferior parietal lobule (IPL), interconnected regions that are part of a hypothesized distributed network concerned with visuospatial analysis or directed attention; in a presumed auditory region of the superior temporal gyrus (STG) and in extrastriate visual cortex, the caudal IPL and lower rim of the intraparietal sulcus; and in dorsal prearcuate cortex and the STG. Overlapping and nonoverlapping projections were then examined in STS visual and polysensory areas. Prefrontal and parietal fibers directly overlapped extensively in area MST and all subdivisions of presumed polysensory cortex (areas TPOc, TPOi, and TPOr), although nonoverlapping connections were also found. Although STG and IPL fibers targeted all TPO subdivisions, connections were to nonoverlapping, but often adjacent, columns. Paired prefrontal and STG injections revealed largely nonoverlapping vertical columns of connections but substantial overlap within layers VI and I or areas TPOc and TPOi. The findings suggest that area TPO contains differently connected modules that may maintain at least initial segregation of visual versus auditory inputs. Other modules within area TPO receive directly converging input from the posterior parietal and the prefrontal cortices and may participate in a distributed cortical network concerned with visuospatial functions.

  6. Influence of prenatal iron deficiency and MAOA genotype on response to social challenge in rhesus monkey infants.

    PubMed

    Golub, M S; Hogrefe, C E; Unger, E L

    2012-04-01

    Social and emotional behaviors are known to be sensitive to both developmental iron deficiency (ID) and monoamine oxidase A (MAOA) gene polymorphisms. In this study, male rhesus monkey infants deprived of dietary iron in utero were compared with iron sufficient (IS) controls (n = 10/group). Half of each group had low MAOA activity genotypes and half had high MAOA activity genotypes. A series of social response tests were conducted at 3-14 months of age. MAOA genotype influenced attention to a video of aggressive behavior, emotional expression (fear, grimace and sniff) in the social intruder test, social actions (displacement, grooming) in the social dyad test, and aggressive responses to a threatening picture. Interactions between MAOA and prenatal ID were seen in response to the aggressive video, in temperament ratings, in affiliative behavior in the social dyad test, in cortisol response in the social buffering test and in response to a social intruder and to pictures with social and nonsocial themes. In general, the effects of ID were dependent on MAOA genotype in terms of both direction and size of the effect. Nutrition/genotype interactions may shed new light on behavioral consequences of nutritional deprivation during brain development.

  7. Sex, acceleration, brain imaging, and rhesus monkeys: Converging evidence for an evolutionary bias for looming auditory motion

    NASA Astrophysics Data System (ADS)

    Neuhoff, John G.

    2003-04-01

    Increasing acoustic intensity is a primary cue to looming auditory motion. Perceptual overestimation of increasing intensity could provide an evolutionary selective advantage by specifying that an approaching sound source is closer than actual, thus affording advanced warning and more time than expected to prepare for the arrival of the source. Here, multiple lines of converging evidence for this evolutionary hypothesis are presented. First, it is shown that intensity change specifying accelerating source approach changes in loudness more than equivalent intensity change specifying decelerating source approach. Second, consistent with evolutionary hunter-gatherer theories of sex-specific spatial abilities, it is shown that females have a significantly larger bias for rising intensity than males. Third, using functional magnetic resonance imaging in conjunction with approaching and receding auditory motion, it is shown that approaching sources preferentially activate a specific neural network responsible for attention allocation, motor planning, and translating perception into action. Finally, it is shown that rhesus monkeys also exhibit a rising intensity bias by orienting longer to looming tones than to receding tones. Together these results illustrate an adaptive perceptual bias that has evolved because it provides a selective advantage in processing looming acoustic sources. [Work supported by NSF and CDC.

  8. Mild Perceptual Categorization Deficits Follow Bilateral Removal of Anterior Inferior Temporal Cortex in Rhesus Monkeys

    PubMed Central

    Matsumoto, Narihisa; Eldridge, Mark A.G.; Saunders, Richard C.; Reoli, Rachel

    2016-01-01

    In primates, visual recognition of complex objects depends on the inferior temporal lobe. By extension, categorizing visual stimuli based on similarity ought to depend on the integrity of the same area. We tested three monkeys before and after bilateral anterior inferior temporal cortex (area TE) removal. Although mildly impaired after the removals, they retained the ability to assign stimuli to previously learned categories, e.g., cats versus dogs, and human versus monkey faces, even with trial-unique exemplars. After the TE removals, they learned in one session to classify members from a new pair of categories, cars versus trucks, as quickly as they had learned the cats versus dogs before the removals. As with the dogs and cats, they generalized across trial-unique exemplars of cars and trucks. However, as seen in earlier studies, these monkeys with TE removals had difficulty learning to discriminate between two simple black and white stimuli. These results raise the possibility that TE is needed for memory of simple conjunctions of basic features, but that it plays only a small role in generalizing overall configural similarity across a large set of stimuli, such as would be needed for perceptual categorical assignment. SIGNIFICANCE STATEMENT The process of seeing and recognizing objects is attributed to a set of sequentially connected brain regions stretching forward from the primary visual cortex through the temporal lobe to the anterior inferior temporal cortex, a region designated area TE. Area TE is considered the final stage for recognizing complex visual objects, e.g., faces. It has been assumed, but not tested directly, that this area would be critical for visual generalization, i.e., the ability to place objects such as cats and dogs into their correct categories. Here, we demonstrate that monkeys rapidly and seemingly effortlessly categorize large sets of complex images (cats vs dogs, cars vs trucks), surprisingly, even after removal of area TE

  9. Use of Lipid Calories during Pneumococcal Sepsis in the Rhesus Monkey

    DTIC Science & Technology

    1982-04-01

    infused with a hy- lipid emulsion ( Intralipid ) effectively prevented this infection- pocaloric amino acid-dextrose solution and an amount of glyc...related loss of body protein. The present study was designed to erol calories equivalent to that found in Intralipid . Under these determine whether the...this the basal solution plus 50 nl/kg/day from a 10% fat infection in the monkey stimulated an increased wasting emulsion ( Intralipid , Cutter

  10. Persistence of the dark-background-contingent gaze upshift during visual fixations of rhesus monkeys.

    PubMed

    Spivak, Oleg; Thier, Peter; Barash, Shabtai

    2014-10-15

    During visual fixations, the eyes are directed so that the image of the target (object of interest) falls on the fovea. An exception to this rule was described in macaque monkeys (though not in humans): dark background induces a gaze shift upwards, sometimes large enough to shift the target's image off the fovea. In this article we address an aspect not previously rigorously studied, the time course of the upshift. The time course is critical for determining whether the upshift is indeed an attribute of visual fixation or, alternatively, of saccades that precede the fixation. These alternatives lead to contrasting predictions regarding the time course of the upshift (durable if the upshift is an attribute of fixation, transient if caused by saccades). We studied visual fixations with dark and bright background in three monkeys. We confined ourselves to a single upshift-inducing session in each monkey so as not to study changes in the upshift caused by training. Already at their first sessions, all monkeys showed clear upshift. During the first 0.5 s after the eye reached the vicinity of the target, the upshift was on average larger, but also more variable, than later in the trial; this initial high value 1) strongly depended on target location and was maximal at locations high on the screen, and 2) appears to reflect mostly the intervals between the primary and correction saccades. Subsequently, the upshift stabilized and remained constant, well above zero, throughout the 2-s fixation interval. Thus there is a persistent background-contingent upshift genuinely of visual fixation.

  11. Personality structure in brown capuchin monkeys (Sapajus apella): comparisons with chimpanzees (Pan troglodytes), orangutans (Pongo spp.), and rhesus macaques (Macaca mulatta).

    PubMed

    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

    2013-08-01

    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 often reflect 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, including 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.

  12. Do rhesus monkeys (Macaca mulatta) perceive the Zöllner illusion?

    PubMed

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

    2014-08-01

    A long-standing debate surrounds the issue of whether human and nonhuman animals share the same perceptual mechanisms. In humans, the Zöllner illusion occurs when two parallel lines appear to be convergent when oblique crosshatching lines are superimposed. Although one baboon study suggests that they too might perceive this illusion, the results of that study were unclear, whereas two recent studies suggest that birds see this illusion in the opposite direction from humans. It is currently unclear whether these mixed results are an artifact of the experimental design or reflect a peculiarity of birds' visual system or, instead, a wider phenomenon shared among nonhuman mammals. Here, we trained 6 monkeys to select the narrower of two gaps at the end of two convergent lines. Three different conditions were set up: control (no crosshatches), perpendicular (crosshatches not inducing the illusion), and Zöllner (crosshatches inducing the illusion in humans). During training, the degrees of convergence between the two lines ranged from 15° to 12°. Monkeys that reached the training criterion were tested with more difficult discriminations (11°-1°), including probe trials with parallel lines (0°). The results showed that monkeys perceived the Zöllner illusion in the same direction as humans. Comparison of these data with the data from bird studies points toward the existence of different orientation-tuned mechanisms between primate and nonprimate species.

  13. Visual expertise does not predict the composite effect across species: A comparison between spider (Ateles geoffroyi) and rhesus (Macaca mulatta) monkeys

    PubMed Central

    Taubert, Jessica; Parr, Lisa A.

    2009-01-01

    Humans are subject to the composite illusion: two identical top halves of a face are perceived as “different” when they are presented with different bottom halves. This observation suggests that when building a mental representation of a face, the underlying system perceives the whole face, and has difficulty decomposing facial features. We adapted a behavioural task that measures the composite illusion to examine the perception of faces in two nonhuman species. Specifically we had spider (Ateles geoffroyi) and rhesus monkeys (Macaca mulatta) perform a two-forced choice, match-to-sample task where only the top half of sample was relevant to the task. The results of Experiment 1 show that spider monkeys (N = 2) process the faces of familiar species (conspecifics and humans, but not chimpanzees, sheep, or sticks), holistically. The second experiment tested rhesus monkeys (N = 7) with the faces of humans, chimpanzees, gorillas, sheep and sticks. Contrary to prediction, there was no evidence of a composite effect in the human (or familiar primate) condition. Instead, we present evidence of a composite illusion in the chimpanzee condition (an unfamiliar primate). Together, these experiments show that visual expertise does not predict the composite effect across the primate order. PMID:19815323

  14. Effects of the monoamine uptake inhibitors RTI-112 and RTI-113 on cocaine- and food-maintained responding in rhesus monkeys.

    PubMed

    Negus, S S; Mello, N K; Kimmel, H L; Howell, L L; Carroll, F I

    2009-01-01

    Cocaine blocks uptake of the monoamines dopamine, serotonin and norepinephrine, and monoamine uptake inhibitors constitute one class of drugs under consideration as candidate "agonist" medications for the treatment of cocaine abuse and dependence. The pharmacological selectivity of monoamine uptake inhibitors to block uptake of dopamine, serotonin and norepinephrine is one factor that may influence the efficacy and/or safety of these compounds as drug abuse treatment medications. To address this issue, the present study compared the effects of 7-day treatment with a non-selective monoamine uptake inhibitor (RTI-112) and a dopamine-selective uptake inhibitor (RTI-113) on cocaine- and food-maintained responding in rhesus monkeys. Monkeys (N=3) were trained to respond for cocaine injections (0.01 mg/kg/inj) and food pellets under a second-order schedule [FR2(V