Adult Male Monkeys Research Articles

Atherosclerotic Lesion of the Carotid Artery in Indonesian Cynomolgus Monkeys Receiving a Locally Sourced Atherogenic Diet.

The atherosclerotic lesion is a principal hallmark of atherosclerotic animal models. This study aimed to assess lesions of the carotid artery in Indonesian cynomolgus monkeys exposed to an IPB-1 atherogenic diet. A total of 20 adult male cynomolgus monkeys received the local IPB-1 diet for two years. Blood lipid profiles, morphology, and carotid ultrasound of monkeys were measured. Nine of them were euthanized to confirm atherosclerotic lesions. Common carotid arteries (CCA) and carotid bifurcation (BIF) samples were collected and stained using Verhoef-van Giessen and CD68 immunohistochemistry. The results reveal the presence of severe atherosclerosis plaques in six out of nine animals (66.7%) corresponding to intermediately and hyper-responsive groups. The hyper-responsive group displayed the highest response in the developing intimal area (IA) at the CCA (0.821 mm2), whereas the hyporesponsive group had the smallest IA (0.045 mm2) (p = 0.0001). At the BIF, the hyporesponsive group showed the smallest IA (p = 0.001), but there was no difference between the intermediately and hyper-responsive groups (p = 0.312). The macrophage marker CD68 was also expressed on the cartotid of the intermediately and hyper-responsive groups. These results indicate that severe atherosclerotic lesions with high infiltration of macrophages were formed in the carotid arteries of intermediately and hyper-responsive Indonesian cynomolgus monkeys fed with the local atherogenic diet IPB-1 over two years, thus confirming atherosclerosis in a nonhuman primate model.

Third-party vocal intervention in the proboscis monkey (Nasalis larvatus)

Vocal intervention is a triadic social interaction, where a third party responds vocally to a conflict between group members, minimizing the costs of aggression in response to the intervention. Because there is little information on vocal third-party intervention in nonhuman mammals, we investigated whether adult male proboscis monkeys use the bray vocalization as a vocal third-party intervention signal to intervene in intragroup conflicts. First, we audio-recorded 1,811 vocalizations from 17 free-ranging proboscis monkey groups in the Lower Kinabatangan Wildlife Sanctuary, analyzing 378 vocal responses of the adult male to agonistic vocal exchanges (shrieks) of group members. Second, we video- and audio-recorded five habituated groups in the Labuk Bay Proboscis Monkey Sanctuary investigating the context of these vocalizations and the conflict dyads evoking vocal support. We found that adult males of one-male/multifemale groups mainly uttered bray vocalizations, whereas females, immatures, and infants uttered shrieks in intragroup conflicts or in response to other animal species. The adult male uttered significantly more often brays after agonistic shrieks than expected based on the overall occurrence of brays. Brays ended 65% of agonistic conflicts, which were accompanied by vocalizations of the conflict partners and occurred more often after conflicts between females than between offspring. This suggests that the bray functions as a vocal third-party intervention signal for intragroup conflict resolution. We suggest that living in the high canopies of the tropical rainforest might restrict direct access to conflict partners and prevent physical intervention, favoring the evolution of the bray as a third-party vocal intervention signal.

Replicability in measures of attentional set-shifting task performance predicting chronic heavy drinking in rhesus monkeys.

This study was designed to replicate and extend a previous report that the increase in performance of an attentional set-shifting task (ASST) in rhesus monkeys predicted their future alcohol drinking status as a heavy drinker (HD) or non-heavy drinker (NHD). A cohort of 6 young adult male monkeys was trained and tested under the same ASST and then underwent a alcohol self-administration protocol that maintained open-access (22 hours/day) choice of alcohol or water 7 days/week for approximately 6 months. The average improvement in performance in the ASST, as measured by a performance index, was replicated in the cohort of 6 monkeys when compared to the increase in the task performance in a previous cohort of 9 male monkeys. The alcohol self-administration protocol was then used to determine the drinking status (HD: n=4 or NHD: n=2) of the replicate cohort, which was accurately predicted by the performance on the ASST. Finally, individuals from both cohorts could be combined based on future drinking status of HD (n=8) or NHD (n=7), and the association with pre-alcohol ASST performance remained. Specifically, monkeys that had lower rates of PI improvement were more likely to become HDs. To our knowledge, this is the first study to replicate that deficits in the set-shifting performance can predict chronic heavy alcohol drinking in primates.

A Preliminary Study on Semen Collection, Its Evaluation, and Testicular and Sperm Morphometries in The Wild Proboscis Monkey (Nasalis Larvatus).

IntroductionThe proboscis monkey (Nasalis larvatus) is an endangered species with a declining population. This article describes the first successful attempt at sperm collection and evaluation, and the testicular and sperm morphometries of the wild proboscis monkey in Sabah, Malaysia.Material and MethodsEight semen collection procedures using electro-ejaculation and digital manipulation were conducted in three wild adult male proboscis monkeys. A total of 21 ejaculates were collected. The testicular biometry was measured with the aid of ultrasonography. Sample evaluation included semen volume and pH and sperm concentration, viability, and abnormality. The sperm morphometry was undertaken using phase contrast microscopy.ResultsThe mean (±SD) total testicular volume of these animals was 5.77 cm3 (±1.58). Semen collection by electro-ejaculation resulted in an 84% success rate, while digital manipulation did not result in any ejaculation. Each animal showed different semen characteristics, where the volume was 5–540 μL, pH 8–9, and sperm concentration 0.041–83.00 ×106/mL. The percentage of abnormal sperm was high at 76.8% (±89.60), largely due to midpiece abnormality. Normal sperm had a spherical head and long tail with a head : midpiece : tail length ratio of 1 : 2: 8.ConclusionThe social status of these animals may contribute to the generally low quality of the semen. The techniques and data from this study are useful for future conservation and application of assisted reproductive technology in this species.

Pegbelfermin, a PEGylated FGF21 analogue, has pharmacology without bone toxicity after 1-year dosing in skeletally-mature monkeys

Pegbelfermin (PGBF) is a PEGylated fibroblast growth factor 21 (FGF21) analogue in development for treatment of nonalcoholic steatohepatitis (NASH). Mouse models highlight potential utility of FGF21 in NASH, but also suggest negative effects on bone, though these findings are confounded by profound FGF21-related decreases in body mass/growth. This study aimed to profile PGBF-related bone effects in adult nonhuman primates after long-term, clinically-relevant exposures. Adult male cynomolgus monkeys received weekly subcutaneous PGBF (0.3, 0.75 mg/kg) or control injections for 1 year (n = 5/group). Assessments included body weight, clinical chemistry, adiponectin levels, bone turnover biomarkers, skeletal radiography, pharmacokinetics, immunogenicity, and histopathology. Bone densitometry and body composition were evaluated in vivo and/or ex vivo with dual-energy x-ray absorptiometry, peripheral quantitative computed tomography, and biomechanical strength testing. After 1 year of PGBF administration, there was clear evidence of sustained PGBF pharmacology in monkeys (peak increase in serum adiponectin of 1.7× and 2.35× pretest at 0.3 and 0.75 mg/kg PGBF, respectively) and decreased body weight compared with control at exposures comparable to those tested in humans. At 0.75 mg/kg PGBF, pharmacologically-mediated reductions in lean mass, lean area, and fat area were observed relative to controls. There were no PGBF-related effects on bone biomarkers, radiography, densitometry, or strength. Together, these data demonstrate that PGBF did not adversely alter bone metabolism, density, or strength following 1 year of dosing at clinically relevant (0.7–2.2× human AUC[0-168 h] at 20 mg once weekly), pharmacologically-active exposures in adult monkeys, suggesting a low potential for negative effects on bone quality in adult humans.

Monkey\u2019s Social Roles Predict Their Affective Reactivity

Accumulating evidence demonstrates that the number of social connections an individual has predicts health and wellbeing outcomes in people and nonhuman animals. In this report, we investigate the relationship between features of an individuals’ role within his social network and affective reactivity to ostensibly threatening stimuli, using a highly translatable animal model — rhesus monkeys. Features of the social network were quantified via observations of one large (0.5 acre) cage that included 83 adult monkeys. The affective reactivity profiles of twenty adult male monkeys were subsequently evaluated in two classic laboratory-based tasks of negative affective reactivity (human intruder and object responsiveness). Rhesus monkeys who had greater social status, characterized by age, higher rank, more close social partners, and who themselves have more close social partners, and who played a more central social role in their affiliative network were less reactive on both tasks. While links between social roles and social status and psychological processes have been demonstrated, these data provide new insights about the link between social status and affective processes in a tractable animal model of human health and disease.

Anticonvulsant effectiveness of scopolamine against soman-induced seizures in African green monkeys

Prolonged seizures are a hallmark feature of intoxication with anticholinesterase nerve agents such as soman. While benzodiazepine drugs are typically used to control these seizures, studies in both rats and guinea pigs have shown that potent, centrally acting anticholinergic drugs such as scopolamine can also terminate such seizures. The present study was performed to determine if scopolamine could produce similar anticonvulsant effects in a nonhuman primate model of soman intoxication. Adult male African green monkeys, implanted with telemetry devices to record cortical electroencephalographic activity, were pretreated with pyridostigmine (0.02 mg/kg, intramuscularly [im]) and 40 min later challenged with 15 µg/kg (im) of the nerve agent soman. One min after soman exposure the animals were treated with atropine (0.4 mg/kg, im) and the oxime 2-PAM (25.7 mg/kg, im). One min after the start of seizure activity the animals were administered scopolamine (0.01–0.1 mg/kg, im), using an up-down dosing design over successive animals. Scopolamine was highly effective in stopping soman-induced seizures with an ED50 = 0.0312 mg/kg (0.021–0.047 mg/kg = 95% confidence limits). Seizure control was rapid, with all epileptiform activity stopping on average 21.7 min after scopolamine treatment. A separate pK study showed that scopolamine absorption peaked approximately 10 min after im administration and a dose of 0.032 mg/kg produced maximum plasma levels of 17.62 ng/ml. The results show that scopolamine exerts potent and rapid anticonvulsant action against soman-induced seizures and that it may serve as a valuable adjunct to current antidote treatments for nerve agent intoxication.

A new primate model of hypophyseal dysfunction

For pituitary regenerative medicine, the creation of a hypophyseal model in monkeys is necessary to conduct future preclinical studies; however, previous studies reported that hypophysectomy in monkeys is not always safe or satisfactory. This study aimed to create a hypophyseal dysfunction model in a cynomolgus monkey using a safer surgical technique and establish the protocol of pituitary hormone replacement therapy for this model. Surgical resection of the pituitary gland of a 7.8-year-old healthy adult cynomolgus male monkey weighing 5.45 kg was performed to create a hypophyseal dysfunction model for future regenerative studies. Endoscopic transoral transsphenoidal surgery was used to perform hypophysectomy under navigation support. These procedures were useful for confirming total removal of the pituitary gland without additional bone removal and preventing complications such as cerebrospinal fluid leakage. Total removal was confirmed by pathological examination and computed tomography. Hypopituitarism was verified with endocrinological examinations including stimulation tests. Postoperatively, the monkey’s general condition of hypopituitarism was treated with hormone replacement therapy, resulting in long-term survival. The success of a minimally invasive and safe surgical method and long-term survival indicate the creation of a hypophyseal dysfunction model in a cynomolgus monkey; hence, this protocol can be employed in the future.

Discriminative-Stimulus Effects of Synthetic Cathinones in Squirrel Monkeys.

BackgroundSynthetic cathinones display overlapping behavioral effects with psychostimulants (e.g., methamphetamine [MA]) and/or entactogens (e.g., 3,4-methylenedioxymethaphetamine [MDMA])—presumably reflecting their dopaminergic and/or serotonergic activity. The discriminative stimulus effects of MDMA thought to be mediated by such activity have been well characterized in rodents but have not been fully examined in nonhuman primates.MethodsThe present studies were conducted to systematically evaluate the discriminative stimulus effects of 5 abused synthetic cathinones (methylenedioxypyrovalerone [MDPV], α-pyrrolidinovalerophenone [α-PVP], methcathinone [MCAT], mephedrone, and methylone) in adult male squirrel monkeys trained to distinguish intramuscular injections of MA (0.1 mg/kg; n = 4) or MDMA (0.6 mg/kg; n = 4) from vehicle.ResultsEach training drug produced dose-dependent effects and, at the highest dose, full substitution. MDMA produced predominantly vehicle-like responding in the MA-trained group, whereas the highest dose of MA (0.56 mg/kg) produced partial substitution (approximately 90% appropriate lever responding in one-half of the subjects) in the MDMA-trained group. MDPV, α-PVP, and MCAT produced full substitution in MA-trained subjects, but, at the same or higher doses, only substituted for MDMA in one-half of the subjects, consistent with primarily dopaminergically mediated interoceptive effects. In contrast, mephedrone and methylone fully substituted in MDMA-trained subjects but failed to fully substitute for the training drug in MA-trained subjects, suggesting a primary role for serotonergic actions in their interoceptive effects.ConclusionsThese findings suggest that differences in the interoceptive effects of synthetic cathinones in nonhuman primates reflect differing compositions of monoaminergic actions that also may mediate their subjective effects in humans.

LC–MS/MS measurement of endogenous oxytocin in the posterior pituitary and CSF of macaques: A pilot study

Oxytocin (OT) is a nanopeptide released into systemic circulation via the posterior pituitary (peripheral) and into the central nervous system via widespread OTergic pathways (central). Central OT plays a significant role in variety of functions from social and executive cognition to immune regulation. Many ongoing studies explore its therapeutic potential for variety of neuropsychiatric disorders. Measures of peripheral OT levels are most frequently used as an indicator of its concentration in the central nervous system in humans and animal models. In this study, LC–MS/MS was used to measure OT in pituitary samples collected from adult male macaque monkeys in order to explore the correlation between individual levels of OT in the CSF (central) and pituitary (peripheral). We quantified individual differences in the levels of OT in the pituitaries (44−151 ng/mg) and CSF (41−66 pg/mL) of these monkeys. A positive correlation between these two measures was identified. These preliminary results allow for future analyses to determine whether LC–MS/MS measures of peripheral OT can be used as markers of OT levels in the brain of nonhuman primates that serve as valuable models for many human neuropsychiatric disorders.

Topographic distribution of the EEG ad hoc broad bands during sleep and wakefulness in the spider monkey (Ateles Geoffroyi).

There is evidence that research on sleep among New World monkeys may provide important knowledge related to the evolution of sleep more broadly in the primate order. Digital electroencephalographic (EEG) analyses provide essential knowledge on sleep in the spider monkey. Recently, specific EEG bands related to sleep in these animals have been obtained using principal component analysis, but the exact spatio-temporal distribution of these EEG bands in this species has not yet been analyzed. This study determined the topographic distribution of the EEG spectral power of ad hoc broad bands during rapid eye movement sleep, nonrapid eye movement sleep, and wakefulness. Superficial EEG activity was obtained from the occipital, frontal, and central areas of six young adult male monkeys housed in a laboratory. During wakefulness, occipital areas showed high absolute power in the 1-3, 3-12, and 11-30 Hz ranges, while during nonrapid eye movement 1 sleep the highest absolute power was in the 13-30 Hz range. During nonrapid eye movement 3 sleep, frontal and central areas showed a high absolute power in the 18-19 Hz range. Finally, the right central area showed a high absolute power in the 20-30 Hz range during rapid eye movement sleep. This topographic distribution of EEG bands could represent the brain organization required for arousal and mnemonic processing during sleep in the spider monkey.

White matter demyelination predates axonal injury after ischemic stroke in cynomolgus monkeys

Unraveling the pathology of stroke is a prerequisite for designing therapeutic strategies. It was reported that myelin injury exceeded axonal loss in the peri-infarct region of rodent white matter stroke. An in-depth investigation of the post-stroke white matter damage in higher-order species might innovate stroke intervention. In this study, adult male cynomolgus monkeys received surgical middle cerebral artery occlusion (MCAO), and serial magnetic resonance scans to non-invasively assess brain damage. Spontaneous movements were recorded to evaluate post-stroke behavior. The axon and myelin loss, as well as immune cell infiltration were examined using immunohistochemistry. Magnetic resonance imaging revealed cerebral infarcts and white matter injury after MCAO in monkeys, which were confirmed by neurological deficits. Immunostaining of white matter fibers showed substantial demyelination whilst retention of axons in the infarcts 8 days post MCAO, while a progressive loss of myelin and axons was observed after one month. Gliosis, microglia activation, and leukocyte infiltration were identified in the lesions. These results demonstrate that demyelination predates axonal injury in non-human primate ischemic stroke, which provides a time window for stroke intervention focusing on prevention of progressive axonal loss through myelin regeneration.

11C]MPC‐6827: A microtubule‐based pet imaging tracer for AD and related dementias

AbstractBackgroundLoss of microtubule (MT) network and impairment of MT function are considered to be part of pathophysiology of several CNS disorders, including AD, Parkinson disease and other ADRS and tauopathies. A BBB penetrating MT‐based PET ligand would permit imaging a variety of CNS disorders. Our lab reported the first brain‐penetrant PET radiotracer [11C]MPC‐6827 to image MTs in vivo, in both wild and transgenic AD mice. Here, we report a pilot longitudinal [11C]MPC‐6827 PET imaging study with early, middle and late stages of Aβ and tau progression in APP/PS1 and P301S mice respectively. PET imaging in NHP brains was performed to test translational utility.MethodDynamic brain microPET/CT imaging was performed with [11C]MPC‐6827 in APP/PS1 mice at 3, 18 and 22 months and in P301S mice (n=4) at 5, and 10 months. Regions of interests (ROIs) were drawn in whole brain, cortex, cerebellum and hippocampus and time‐activity curves (TACs) were determined. Basic distribution volume ratios (DVRs) between high‐ and low‐uptake regions were calculated. Dynamic 2h PET/CT imaging was performed in adult male vervet monkeys (n=8).ResultBased on ROIs and TACs in whole brain, cortex and hippocampus, the radioactive uptake of 3 month‐old TG APP/PS1 mice was ∼30% higher compared to the uptake at 18 months, which in turn was ∼18% higher over 22 month‐old mice. Radioactive uptake of TG P301S mice at 5 months was ∼24% higher compared to 10‐month old mice. DVRs from cortex and hippocampus to cerebellum were ∼2‐fold higher in younger APP‐PS1 and P301S mice compared to their older littermates. Radioactive changes in all experiments were statistically significant, substantiating our preliminary imaging data. NHP‐PET brain analyses indicated brain penetration and high retention of the tracer.Conclusion[11C]MPC‐6827 demonstrated decreased radioactive uptake with increased brain Aβ and tau loads. A MT‐based PET imaging tracer could be a potential early imaging biomarker for AD and other ADRDs. PET imaging studies in monkey brains showed high BBB penetration. Binding distribution is in good agreement with the known MT‐mice distribution. Next steps are to correlate radioactive uptake with tau pathologies and in an NHP model of AD.

Effects of long-term cocaine self-administration on brain resting-state functional connectivity in nonhuman primates

Long-term cocaine use is associated with a variety of neural and behavioral deficits that impact daily function. This study was conducted to examine the effects of chronic cocaine self-administration on resting-state functional connectivity of the dorsal anterior cingulate (dACC) and putamen—two brain regions involved in cognitive function and motoric behavior—identified in a whole brain analysis. Six adult male squirrel monkeys self-administered cocaine (0.32 mg/kg/inj) over 140 sessions. Six additional monkeys that had not received any drug treatment for ~1.5 years served as drug-free controls. Resting-state fMRI imaging sessions at 9.4 Tesla were conducted under isoflurane anesthesia. Functional connectivity maps were derived using seed regions placed in the left dACC or putamen. Results show that cocaine maintained robust self-administration with an average total intake of 367 mg/kg (range: 299–424 mg/kg). In the cocaine group, functional connectivity between the dACC seed and regions primarily involved in motoric behavior was weaker, whereas connectivity between the dACC seed and areas implicated in reward and cognitive processing was stronger. In the putamen seed, weaker widespread connectivity was found between the putamen and other motor regions as well as with prefrontal areas that regulate higher-order executive function; stronger connectivity was found with reward-related regions. dACC connectivity was associated with total cocaine intake. These data indicate that functional connectivity between regions involved in motor, reward, and cognitive processing differed between subjects with recent histories of cocaine self-administration and controls; in dACC, connectivity appears to be related to cumulative cocaine dosage during chronic exposure.

11C]MPC‐6827, a microtubule‐based PET imaging tracer: A potential early imaging biomarker for AD and other ADRDs

AbstractBackgroundLoss of microtubule (MT) network and impairment of MT function are considered to be part of the pathophysiology of several CNS disorders, including AD, Parkinson disease and other ADRS and tauopathies. A BBB penetrating MT‐based PET ligand would permit imaging a variety of CNS disorders. Our lab reported the first brain‐penetrant PET radiotracer [11C]MPC‐6827 to image MTs in vivo, in both wild and transgenic AD mice. Here, we report a pilot longitudinal [11C]MPC‐6827 PET imaging study with early, middle and late stages of Aβ and tau progression in APP/PS1 and P301S mice respectively. PET imaging in NHP brains was performed to test translational utility.MethodDynamic brain microPET/CT imaging was performed with [11C]MPC‐6827 in APP/PS1 mice at 3, 18 and 22 months and in P301S mice (n=4) at 5, and 10 months. Regions of interest (ROIs) were drawn in whole brain, cortex, cerebellum and hippocampus and time‐activity curves (TACs) were determined. Basic distribution volume ratios (DVRs) between high‐ and low‐uptake regions were calculated. Dynamic 2h PET/CT imaging was performed in adult male vervet monkeys (n=8).ResultBased on ROIs and TACs in whole brain, cortex and hippocampus, the radioactive uptake of 3 month‐old TG APP/PS1 mice was ∼30% higher compared to the uptake at 18 months, which in turn was ∼18% higher over 22 month‐old mice. Radioactive uptake of TG P301S mice at 5 months was ∼24% higher compared to 10‐month old mice. DVRs from cortex and hippocampus to cerebellum were ∼2‐fold higher in younger APP‐PS1 and P301S mice compared to their older littermates. Radioactive changes in all experiments were statistically significant, substantiating our preliminary imaging data. NHP‐PET brain analyses indicated brain penetration and high retention of the tracer.Conclusion[11C]MPC‐6827 demonstrated decreased radioactive uptake with increased brain Aβ and tau loads. A MT‐based PET imaging tracer could be a potential early imaging biomarker for AD and other ADRDs. PET imaging studies in monkey brains showed high BBB penetration. Binding distribution is in good agreement with the known MT‐mice distribution. Next steps are to correlate radioactive uptake with tau pathologies and in an NHP model of AD.

Human-monkey interaction dynamics and their dietary impacts on central american white-faced capuchins (<i>Cebus imitator</i>) at Manuel Antonio National Park, Costa Rica


 
 
 Wild capuchin monkeys are highly adaptable to anthropogenic environments. We assessed how the interaction dynamics between humans and three groups of Panamanian white-faced capuchin monkeys (Cebus imitator) in Manuel Antonio National Park, the most visited national park of Costa Rica, affected the feeding behavior and diet of these animals in 2008-2009. On average, individual monkeys acquired 2.4 human food items per focal hour during peak hours of park visitation by humans. Although human visitors directly and indirectly provisioned monkeys in the park, 71 % of monkeys’ acquisition of human food items were a result of monkey-initiated interactions (MIIs) rather than human-initiated interactions (HIIs), and adult male monkeys were the most frequent initiators (with 157 adult male MIIs in the study period, compared to 33 initiated by adult females and 84 by juveniles). Adult male monkeys were also the most likely to make direct contact with humans to grab food (35 of 50 direct grabs of food from humans were by adult male monkeys). Adult females acquired food from humans through HIIs at about the same rate as adult males in their group. Secondary acquisition of human food from other monkeys accounted for about one-third of all events of monkey acquisition of human food, and juvenile monkeys had higher median hourly rates than adults in their group to acquire human food through secondary acquisition. Humans frequently offered fruit when provisioning (61.4 % of provisioning events), but monkeys actively acquired fruit, meat, candy, condiments, chips, crackers and dairy items, and only 36.5 % of MIIs were to acquire fruit. Our results suggest that in parks where humans have frequent contact with capuchin monkeys, park regulations should not only prohibit direct provisioning, but require visitors not to bring food into parks. Stronger measures such as fines or park expulsion for those interacting with monkeys might be more effective, and environmental education is necessary as a strategy to inform visitors what to expect from the monkeys and how to avoid accidental provisioning.
 
 

KAJIAN TINGKAH LAKU MONYET EKOR PANJANG (Macaca Fascicularis) OBES DALAM KANDANG INDIVIDU

STUDY ON BEHAVIOUR OF THE LONG TAIL MONKEY (Macaca fascicularis) OBESE IN INDIVIDUAL CAGE. This study was designed to obtain information of development behaviour the obesity of long-tailed monkey (Macaca fascicularis) fed with high energy obes diet. The need of obese monkeys highly to model byomedis obesity. Obesity is now a universal problem that needs to be explored and studied. Therefore, the objective of this research was to develop obese adult male monkeys with high energy food for 12 months and monitoring their behaviour. Fifteen adult male monkeys 6-8 years old with the weight of between 4-5 kg were divided equally into three groups. The first group was body weight average 4.50 kg, the second group was body weight average 5.00 kg; and the third group was body weight average 4.75 kg. The results showed that body weight gave a significant effect (P <0.01) on daily behaviour and also gave a significant effect (P<0.01) on fed behaviour frequently,drink behaviour, agonistic behaviour, grooming behaviour, and locomotion behaviour .Keywords: Behaviour frequently, Long-tailed monkey (Macaca fascicularis), Obesity)

Peripheral Administration of RF9 Does Not Affect Hypothalamic-PituitaryGonadal Axis in Normal Fed Adult Male Macaque

Stress represses hypothalamic-pituitary-gonadal axis (HPG-axis) but RF9, a synthetic peptide, rescues such repression. To assess the role of RF9 in regulating HPG-axis under normal physiological conditions in higher primates, RF9 was administered to intact adult male rhesus monkeys and response of the HPG-axis was examined by measuring plasma testosterone as an end parameter of the axis. Control group (n=4) received normal saline whereas the treated group (n=4) received RF9. On the first day of experiment, four bolus injections of normal saline (1ml/animal) were administered intravenously at 2-hr interval to the control monkeys. Similarly, on the second day of experiment, treated group received four iv bolus injections of RF9 (0.1mg/kg BW) at 2-hr interval. Serial blood samples were collected at 20 min interval during a 6-hr period which started just after first saline/RF9 injection. Plasma testosterone levels were measured by using a specific EIA. Overall means of plasma testosterone levels and plasma testosterone area under curve (AUC) and overall mean testosterone and mean testosterone AUC in short time windows following each injection of RF9 and saline were comparable between the groups. Our results demonstrate that RF9 has no role in regulating HPG-axis under normal physiological conditions in adult male monkeys.

Carfentanil toxicity in the African green monkey: Therapeutic efficacy of naloxone

Carfentanil is an ultra-potent opioid with an analgesic potency 10,000 times that of morphine but has received little scientific investigation. Three experiments were conducted to evaluate the toxicity of carfentanil and the efficacy of naloxone in adult male African green monkeys. The first experiment determined the ED50 (found to be 0.71 μg/kg) of subcutaneous carfentanil for inducing bradypnea and/or loss of posture. Experiment 2 attempted to establish the ED50 of naloxone for rapidly reversing the bradypnea/loss of posture induced by carfentanil (1.15 μg/kg). Experiment 3 evaluated the effects of carfentanil (0.575 μg/kg) alone, the safety of naloxone (71−2841 μg/kg), and the efficacy of naloxone (71−710 μg/kg) administration at two time points following carfentanil (1.15 μg/kg) on operant choice reaction time. Collectively, these experiments characterized the temporal progression of carfentanil-induced toxic signs, determined the range of naloxone doses that restored respiratory and gross behavioral function, and determined the time course and range of naloxone doses that partially or completely reversed the effects of carfentanil on operant choice reaction time performance in African green monkeys. These results have practical relevance for the selection of opioid antagonists, initial doses, and expected functional outcomes following treatment of synthetic opioid overdose in a variety of operational/emergency response contexts.

Development of a novel gripping test for the evaluation of the finger fine motor ability in MPTP-treated monkeys

Assessing the finger fine motor ability is extremely important. However, conventional behavioral tests in monkeys are complicated and costly. We attempted to develop a new task to assess the precise finger grip in Parkinson's disease monkeys based on the principles of objectification, multipurpose, and simplification. This study involved seven adult male cynomolgus monkeys. A gripping test based on the previous food reaching test was developed. Parallel experiments of food reaching test and gripping test affected by the treatments of levodopa and deep brain stimulation of the subthalamic nucleus were performed to verify the utility of the gripping test. We found that gross motor ability (measured by food reaching test) could be significantly improved by both the subthalamic nucleus and levodopa administration, which reproduced the results of our previous study. The finger fine motor ability (measured by the gripping test) could be significantly improved by levodopa administration, but not by the subthalamic nucleus. Our results verified the utility and reliability of the gripping test, which is a simple, convenient, and objective task for evaluating the finger fine motor skill in Parkinson's disease monkeys. Mechanisms of the efficacy of deep brain stimulation on fine motor ability require further investigation.