Establishment of small breeding colony of rhesus monkeys.

A breeding colony of 22 female and 4 male rhesus monkeys (Macaca mulatta) was established in a controlled-environment building with an outdoor run. The animals were quarantined for 2 years prior to their release into the unit. The housing, release and management of the colony are described. During the first year 19 young were born of which 17 have survived to 6 months of age. The cost of production and maintenance of the colony when compared with the cost of importing rhesus monkeys would appear to be acceptable.     

Menstrual cycle characteristics of seasonally breeding rhesus monkeys

Rhesus monkeys in seminatural environments exhibit a distinct seasonal mating cycle with conceptions restricted to the fall and winter months. In the present study, the characteristics of menstrual cycles were examined during a 1-year period in twelve rhesus monkeys in whom pregnancy was prevented. Menses occurred throughout the year, but ovulations were observed only in the fall and winter months. Menses in the spring and summer months occurred irregularly and were associated exclusively with anovulatory cycles. The total number of ovulations exhibited by these females during the breeding season ranged from two to six and was positively related to body weight, mean luteal phase progesterone (P) levels of normal cycles and social dominance rank. Ovulations with a short luteal phase were exhibited by four females (seven cycles), with the likelihood of occurrence increasing as the breeding season progressed. The incidence of abnormal cycles was predicted from the linear combination of parity, body weight and luteal phase P of normal ovulatory cycles. These results suggest that during the seasonally delimited period of ovulation, females exhibit a range in the quality and quantity of ovulations which may be predicted by certain idiosyncratic physical and behavioral traits.     

Establishing a free-ranging breeding colony of rhesus monkeys. Part I.

The Caribbean Primate Research Center recently contracted with the Food and Drug Administration to establish a free-ranging island breeding colony of rhesus monkeys. The goal of the program is to produce 600 to 800 offspring yearly from 1,000 breeding age females. The initial colony stock will consist of approximately 360 animals from an existing colony that was established on an island off the southwestern coast of Puerto Rico in 1961. Expansion of the colony will be accomplished by the purchase and introduction of rhesus females obtained from the wild. The colony site, reproductive history, composition, and the methodology of our expansion plans are discussed. In addition, anticipated problems are identified and analyzed.     

Increased fertility in rhesus monkeys by breeding after the preovulatory LH surge.

Fertility in a rhesus monkey breeding colony was significantly increased by caging females with males immediately after detection of the preovulatory luteinizing hormone (LH) surge. LH was measured in daily serum samples by a rapid (24-hr) radioimmunoassay which used iodinated ovine LK as tracer and an antiserum to human LH.     

Seasonal breeding in rhesus monkeys: Influence of the behavioral environment

The accepted model of breeding seasonality in rhesus monkeys states that females become reproductively active in response to an environmental cue and that males become sexually active in response to ovulating females. This model must be modified to include direct responses of the male to the physical environment, endocrine responses of males to sexual activity, and responses of the female to the sexual activation of fellow group members. The complex set of social stimuli that influences the breeding readiness of both sexes may serve to delimit more precisely the annual periods of conception and birth than would be the case if each individual responded only to the changing physical environment.     

Effects of aphakia on the geniculostriate system of infant rhesus monkeys.

The effects on the visual system of rearing rhesus monkeys with monocular aphakia, corrected with extended-wear contact lenses, were assessed with anatomical, electrophysiological and behavioral methods. The major finding was that the effects of the various treatments on the aphakic eye varied in degree depending upon the amount of focused pattern input received by the aphakic eye compared to its fellow eye. The behavioral, electrophysiological and anatomical assessments of the treatment effects on the aphakic eyes correlated closely with each other. Because this experimental paradigm is similar to current clinical procedures for treating human infantile monocular cataracts, it provides a nonhuman primate model for studying aphakia.     

Resumption of seasonal breeding patterns in male and female rhesus monkeys transferred from an indoor to an outdoor environment

Seasonal aspects of social behavior and sex steroid levels were observed in two groups of rhesus monkeys from March through December. One group (3 males, 7 females) had lived outdoors for several years. The other group (6 males, 5 females), transferred outdoors in late February, had lived indoors for several years. In March-April, the long-term outdoor residents displayed the expected seasonal pattern of sexual behavior, characterized by absence of complete sequences of copulatory behavior. At this time the indoor-adapted group displayed high levels of copulatory behavior. Thereafter, frequencies of sexual behavior of the two groups were similar. Testosterone in the males was positively correlated with frequency of sexual behavior in each group. Females in the indoor-adapted group displaced menstrual cycles in March and April and 3 of 5 became pregnant at this time. The two remaining indoor-adapted females continued to display ovulatory cycles, but little sexual behavior, throughout the summer. Interestingly, two females in the outdoor-adapted group also displayed summer ovulatory cycles; without concomitant sexual activity. These data show that the disruption of seasonal breeding patterns produced by lengthy indoor housing remains briefly apparent following transfer outdoors, but is substantially overcome within a few months.     

Interspecies embryo transfer between rhesus and cynomolgus monkeys

正Nonhuman primates (NHPs) present significant advantages over rodents for physiological and pharmacological investigations because of their higher genetic and physiological similarity to humans. Both rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) monkeys are considered ideal animal models in biomedical research (Phillips et al., 2014), especially in modeling normal development and diseases in the nervous system (Izpisua Belmonte et al., 2015; Ng et al., 2015; Niu et al., 2015; Poo et al.,     

Effects of atropine on operant test battery performance in rhesus monkeys.

The acute behavioral effects of atropine sulfate were assessed using a battery of complex food-reinforced operant tasks that included: temporal response differentiation (TRD, n = 7); delayed matching-to-sample (DMTS, n = 6), progressive ratio (PR, n = 8), incremental repeated acquisition (IRA, n = 8), and conditioned position responding (CPR, n = 8). Performance in these tasks is thought to depend primarily upon specific brain functions such as time perception, short-term memory and attention, motivation, learning, and color and position discrimination, respectively. Atropine sulfate (0.01-0.56 mg/kg iv), given 15-min pretesting, produced significant dose-dependent decreases in the number of reinforcers obtained in all tasks. Response rates decreased significantly at greater than or equal to 0.03 mg/kg for the learning and discrimination tasks, at greater than or equal to 0.10 mg/kg for the motivation and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Response accuracies were significantly decreased at doses greater than or equal to 0.10 mg/kg for the learning, discrimination, and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Thus, the order of task sensitivity to any disruption by atropine is learning = color and position discrimination greater than time perception = short-term memory and attention = motivation (IRA = CPR greater than TRD = DMTS = PR). Thus in monkeys, the rates of responding in operant tasks designed to model learning and color and position discrimination were the most sensitive measures to atropine's behavioral effects. Accuracy in these same task was also disrupted but at higher doses. These data support the hypothesis that cholinergic systems play a greater role in the speed (but not accuracy) of performance of our learning and discrimination tasks compared to all other tasks. Accuracy of responding in these and the short-term memory task, all of which involve the use of lights as visual stimuli, was more sensitive to disruption by atropine than those tasks which did not utilize such strong visual stimuli.     

Effects of lead on luteal function in rhesus monkeys

Exposure to lead in the workplace or home environment has been implicated as a cause of decreased fertility in women. In a previous study, as part of our effort to determine effects of lead in primates, female rhesus monkeys were exposed to lead acetate in drinking water (n = 10) or provided water with no added lead (n = 7) for 33 mo. Lead was administered at levels between 2 and 8 mg/kg/day, with doses adjusted to keep blood lead values near a target of 70 micrograms/dl (observed mean +/- SEM = 68.9 +/- 6.54 micrograms/dl). Blood lead concentrations in control animals were less than 10 micrograms/dl. No significant differences were detected between control and experimental animals in body weight, hematocrit, or general health. Female monkeys receiving lead exhibited longer and more variable menstrual cycles and shorter menstrual flow. In the present study, circulating amounts of progesterone (P4) were determined to evaluate luteal function during the final 7 mo of treatment with lead. Several characteristics were altered as a result of lead treatment: circulating amounts of P4 were reduced as indicated by relative units of area under the concentration-time curve, maximal amounts of P4 were reduced, and P4 levels were greater than 1 ng/ml on fewer days. There were no significant differences between groups in mean percent of anovulatory cycles. Therefore, although chronic treatment with the levels of lead used in this study did not prevent ovulation, luteal function was suppressed. These results extend previous observations of adverse effects of lead on ovarian activity and fertility in monkeys.     

Effects of fenofibrate on lipid parameters in obese rhesus monkeys

Fenofibrate is a member of the fibrate class of hypolipidemic agents used clinically to treat hypertriglyceridemia and mixed hyperlipidemia. The fibrates were developed primarily on the basis of their cholesterol and triglyceride lowering in rodents. Fibrates have historically been ineffective at lowering triglycerides in experimentally-induced dyslipidemia in nonhuman primate models. The spontaneously obese rhesus monkey is a well-recognized animal model for the study of human obesity and type 2 diabetes, and many of these monkeys exhibit naturally occurring lipid abnormalities, including elevated triglycerides and low HDL cholesterol (HDL-C), similar to patients with type 2 diabetes. To explore whether the obese rhesus model was predictive of the lipid lowering effects of fibrates, we evaluated fenofibrate in six hypertriglyceridemic, hyperinsulinemic, nondiabetic animals in a 20-week, dose-escalating study. The study consisted of a 4-week baseline period, two treatment periods of 10 mg/kg twice daily (b.i.d) for 4 weeks and 30 mg/kg b.i.d. for 8 weeks, and a 4-week washout period. Fenofibrate (30 mg/kg b.i.d) decreased serum triglycerides 55% and LDL-C 27%, whereas HDL-C increased 35%. Apolipoproteins B-100 and C-III levels were also reduced 70% and 29%, respectively. Food intake, body weight, and plasma glucose were not affected throughout the study. Interestingly, plasma insulin levels decreased 40% during the 30 mg/kg treatment period, suggesting improvement in insulin sensitivity. These results support the use of obese rhesus monkey as an excellent animal model for studying the effects of novel hypolipidemic agents, particularly agents that impact serum triglycerides and HDL-C.     

Japanese monkey group translocation: Effects on seasonal breeding

A 150-member troop of Japanese monkeys (Macaca fuscata)was translocated from its temperate native habitat, near Kyoto, Japan, to a 42-ha enclosure near Laredo, Texas, in February 1972. The seasonal timing and distribution of 430 births recorded over the period 1954–1971 were compared to those of 186 births recorded in Texas from 1973 to 1979. Despite striking climatological and environmental differences between the pre- and the postranslocation sites, the timing of the birth season remaines unchanged, although the distribution of births was altered. These findings, considered in light of other published data on the seasonality of mating in macaques, suggest that a phenomenon akin to social drift may account for much of the intertroop variation that occurs.     

Four-year study of controlled timed breeding of rhesus monkeys (Macaca mulatta)

As part of the timed breeding colony at Tulane National Primate Research Center, exogenous progesterone administration (5 mg/day for 10 days) has been used to select conception dates by inducing artificial luteal phases in female rhesus monkeys. A retrospective analysis of data obtained during four breeding seasons (1998-2001) revealed that conceptions occurred an average of 18 days after the last administration of progesterone. The age of the female to be bred, previous pregnancy history, and timing of breeding during the breeding season were determined to be critical factors in the success of the procedure. The benefit of this method of timed breeding is that it does not require tracking of menstrual cycles, which can be labor-intensive and requires that animals be monitored several months in advance of breeding to determine each female's individual cycle length. It also provided an efficient use of breeding-age males.     

Persistent adrenocortical activation in female rhesus monkeys after new breeding groups formation

Persistent elevated adrenocortical responsiveness to ACTH has been demonstrated in female rhesus monkeys as long as 13 weeks after relocation into new single male breeding groups. Measures of immediate responses to psychosocial stress of grouping such as aggressive interaction and circulating plasma cortisol levels were highest immediately after grouping, but tended to decline to lower levels after the first month. In a retrospective comparison of such 'new' breeding groups (less than one year) versus established breeding groups (more than two years), stress-related morbidities such as trauma (wounding) and loose stools were higher for as long as six months after new group formation. The actual and potential adverse effects of regrouping stress on colony health and reproduction are relevant to cost-benefit assessment of such colony management procedures.     

Behavioural and hormonal responses of male rhesus monkeys introduced to females in the breeding and non-breeding seasons.

Six adult male rhesus monkeys were introduced individually to an all-female group for 10 days during the mating season. The initial aggressive responses of the females were rapidly replaced by positive social behaviour, and each male achieved alpha status and had access to social and sexual partners. A repetition of this paradigm in the non-breeding season produced significantly more female aggression, and no male attained high rank or engaged in sexual or other social behaviour. Male testosterone levels rose following introduction to the females in both seasons, but were significantly higher during the breeding season. Hormonal levels following removal from the females suggest a complex interplay between social, sexual and seasonal variables and recent social experiences. The differences in female social behaviour with newly introduced males, as a function of season, suggest an explanation for the seasonal limitation of male troop transfers.     

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

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.     

Effects of dietary caloric restriction and aging on thyroid hormones of rhesus monkeys.

Plasma levels of thyroid hormones - triiodothyronine (T 3 ), thyroxin (T 4 ), and thyroid-stimulating hormone (TSH) were measured in male and female rhesus monkeys (Macaca mulatta) fed either ad libitum or a 30 % calorie-restricted (CR) diet (males for 11 years; females for 6 years). The same hormones were measured in another group of young male rhesus monkeys during adaptation to the 30 % CR regimen. Both long- and shorter-term CR diet lowered total T 3 in plasma of the monkeys. The effect appeared to be greater in younger monkeys than in older counterparts. No effects of CR diet were detected for either free or total T 4, although unlike T 3, levels of this hormone decreased with age. TSH levels also decreased with age, and were increased by long-term CR diet in older monkeys only. No consistent effects of shorter-term CR diet were observed for TSH. In the light of the effects of the thyroid axis on overall metabolism, these results suggest a possible mechanism by which CR diets may elicit their well-known beneficial 'anti-aging' effects in mammals.