Social instability and immunity in rhesus monkeys: the role of the sympathetic nervous system

Social instability can adversely affect endocrine, immune and health outcomes, and recent evidence suggests that the sympathetic nervous system (SNS) might mediate these effects. We conducted two studies with adult male rhesus monkeys (Macaca mulatta) to understand how social conditions affect measures of SNS activity and immune function. In Experiment 1, animals were socialized in stable social conditions, then were switched to unstable (stressful) social conditions, then were returned to stable conditions. Analysis revealed quadratic effects for measures of behaviour, urinary metabolites of epinephrine and norepinephrine, and expression of immune response genes: as expected, social instability adversely impacted most measures, and the effects remediated upon re-imposition of stable conditions. Cortisol levels were unaffected. In Experiment 2, we used the sympathomimetic drug methamphetamine to challenge the SNS; animals also underwent socialization in stable or unstable groups. Surprisingly, while methamphetamine elevated plasma catecholamines, responses in lymph nodes tracked the social, and not the drug, condition: social instability upregulated the density of SNS fibres in lymph nodes and downregulated Type I interferon gene expression. Together, these results indicate that the SNS is extremely sensitive to social conditions; full understanding of the adverse effects of social instability on health should therefore incorporate measures of this health-relevant system.     

Ovarian response to gonadotropin stimulation in juvenile rhesus monkeys

The objective of this study was to investigate juvenile rhesus monkeys responding to various gonadotropin regimen stimulations. Thirty-two prepubertal rhesus monkeys were randomly allocated into five groups for ovarian stimulation as follows: Groups I, II, and III were given 35, 18, and 9 IU recombinant human follicle-stimulating hormone (rhFSH), respectively, twice daily for 8 d; Group IV was given 18 IU rhFSH twice daily until the appearance of maximal increase in sex skin during the breeding season; and Group V was treated identically to Group II but during the nonbreeding season. In addition, nine menarchial monkeys (Group VI) were treated identically to Group II. Menarchial monkeys yielded two- to fivefold the numbers of MII oocytes (24.1) and almost twice the development potential of in vitro-fertilized oocytes (blastocyst rate: 50.0%) compared with those of the other groups. Moreover, prepubertal monkeys in Group V had approximately double the numbers of MII oocytes and in Groups IV and V twice the development potential compared with those of Groups I and II, whereas Group III did not respond to stimulation. The most prominent sex skin swelling was in association with peak serum estradiol concentrations, and good responses to stimulation were associated with reduced body temperatures. All stimulated monkeys had normal reproductive performance at adulthood, except those in Group I. In conclusion, gonadotropin stimulation of menarchial monkeys could be appropriate for addressing the high cost and limited availability of rhesus monkeys in studying reproductive biology in primates.     

Self-agency in rhesus monkeys

Rhesus monkeys (Macaca mulatta) have shown the ability to monitor their own mental states, but fail the mirror self-recognition test. In humans, the sense of self-agency is closely related to self-awareness, and results from monitoring the relationship between intentional, sensorimotor and perceptual information. Humans and rhesus monkeys were trained to move a computer icon with a joystick while a distractor icon partially matched their movements. Both humans and monkeys were able to monitor and identify the icon they were controlling, suggesting they have some understanding of self-agency.     

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.     

Superovulatory response to a low dose single-daily treatment of rhFSH dissolved in polyvinylpyrrolidone in rhesus monkeys

To simplify the procedure for superovulation in the rhesus monkey, this study was designed using polyvinylpyrrolidone (PVP) solution as a solvent for gonadotropins. Thirty-five cycling females (aged 5-8 years old) were divided into six groups during the breeding season (November- February). The groups were as follows: Group I, animals received twice-daily 35 IU recombinant human follicle-stimulating hormone (rhFSH) dissolved in 0.5 ml saline for 8 days as the control; Groups II and III, animals received single-daily 35 IU and 17 IU rhFSH in 0.5 saline, respectively, for 9 days; Groups IV, V and VI, received single-daily injection of 35 IU rhFSH, 17 IU rhFSH and 8.5 IU rhFSH dissolved in 0.5 ml 30% PVP (w/v) solution, respectively, for 9 days. After human chorionic gonadotropin was administered to induce the nuclear maturation of oocytes, oocytes were retrieved and the development competence of recovered oocytes treated with in vitro fertilization were observed. The plasma concentrations of follicle-stimulating hormone and ovarian responses were monitored during the treatment. The results showed that the number of recovered oocytes and the in vitro developmental competence of mature oocytes was equivalent among monkeys when treated with a single-daily treatment of 17 and 35 IU rhFSH with PVP preparation in Groups IV and V compared with the twice-daily 35 IU rhFSH treatments received by Group I. However, almost all animals in Groups II, III and VI responded poorly to corresponding stimulations. These findings indicate that a single-daily low dose of rhFSH dissolved in PVP solution can induce the satisfactory ovarian responses in rhesus monkeys. This has the potential to reduce treatment distress, stress to the animals, the labor of the operator as well as the amount of rhFSH used in ovarian stimulation, compared with traditional superovulation methods.     

Cortisol response of female rhesus monkeys to venipuncture in homecage versus venipuncture in restraint apparatus

Cortisol response of ten single-caged adult female rhesus monkeys during venipuncture in a restraint apparatus was compared with cortisol response of ten paired and five single-caged adult female rhesus monkeys during venipuncture in the homecage. Results demonstrated that in-homecage venipuncture offers a methodological improvement for research protocols that require blood collection of undisturbed animals.     

Effects of age,rearing, and separation stress on immunoglobulin levels in rhesus monkeys

The study reported here examined the effect of different rearing conditions and psychological stress on immunoglobulin levels in rhesus monkey infants. In the first experiment, 24 rhesus neonates were placed in one of the three following rearing conditions: Separated from their mothers and reared in the laboratory nursery; kept with their biological mothers; or removed at birth from their biological mothers and cross-fostered to adoptive rhesus mothers. Plasma samples were obtained from the nursery-reared infants immediately after birth and at weekly intervals for the next 30 days. Samples were also obtained from mother-reared and foster-reared infants on days 15 and 29. All samples were tested for IgG and IgM levels. The results indicated that neither rearing nor diet affected Ig levels. IgG levels were highest at birth and decreased progressively for the first 30 days, suggesting that placental transfer of maternal IgG is the critical determinant of IgG levels in primate infants as in humans. IgM changes were also similar to those in human infants: Low levels at birth, a significant increase from birth to day 15, and a moderate decline from day 15 to day 30. When IgG levels and IgM levels were correlated across the first month, many significant correlations were found which were consistent with human data relating both infant IgG and IgM levels to infant maturation. In the second experiment, 11 of the previously tested nursery infants were subjected to four consecutive social separations from peer groups at 6 months of age. Plasma samples were obtained before and after the first and fourth weeks of separation and tested for IgG and IgM levels. Small but significant decreases in both immunoglobulins were detected after 4 days of separation, particularly on the fourth week.     

Relative numerical middle in rhesus monkeys

Animals show vast numerical competence in tasks that require both ordinal and cardinal numerical representations, but few studies have addressed whether animals can identify the numerical middle in a sequence. Two rhesus monkeys (Macaca mulatta) learned to select the middle dot in a horizontal sequence of three dots on a touchscreen. When subsequently presented with longer sequences composed of 5, 7 or 9 items, monkeys transferred the middle rule. Accuracy decreased as the length of the sequence increased. In a second test, we presented monkeys with asymmetrical sequences composed of nine items, where the numerical and spatial middle were distinct and both monkeys selected the numerical middle over the spatial middle. Our results demonstrate that rhesus macaques can extract an abstract numerical rule to bisect a discrete set of items.     

The human Duffy blood group in rhesus monkeys1

There is good evidence that susceptibility to Plasmodium vivax infection and to P. knowlesi erythrocyte invasion is influenced by certain human Duffy (Fy) blood group antigens. Since P. knowlesi readily infects rhesus monkeys (Macaca mulatto), it was not surprising to find an Fy-like antigen on rhesus erythrocytes. Using human Fy antisera in elution and absorption experiments, we found that all 40 rhesus monkeys tested displayed the Fy(a-b +) phenotype. Furthermore, the rhesus Fy^bantigen was inactivated by chymotrypsin but not by trypsin, suggesting that it is homologous to the human Fy^bantigen. Preliminary serological analyses and enzyme hydrolysis experiments suggest that none of the 13 blood group systems that we have described in rhesus are analogous to the human Fy system. Thus, it appears that there is no Duffy-like polymorphism in rhesus monkeys.     

Skeptical responding in rhesus monkeys (Macaca mulatta)

Signalers that misinform sufficiently open may become devalued as sources of information; however, “skepticism” and any comparison involved in testing reliability entail a cost that involves delays and energy expenditure. Skepticism may be less costly though, if, as a rule, animals are not equally skeptical of the signals of all conspecifics. Animals with the ability to recognize individual conspecifics and to recall past encounters with them may have the capacity to restrict skepticism to subsets of animals that are most likely to benefit from deception. We played tape-recorded alarm calls of high- and low-ranking rhesus monkeys(Macaca mulatta) to their groups in a feeding context once daily over 8 consecutive days at the Yerkes Primate Center Field Station. Over the sequence of playbacks, response was greater to the calls of high-ranking monkeys, adult response patterns were different from those of juveniles, and for adults especially, decline in responsiveness was punctuated by partial resurgences of response. These differences may be the consequence of the adults’ more extensive histories of interaction with group members that, though generally reliable, vary with respect to the potential benefits of deceptive signaling.     

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.     

Water metabolic parameter changes in rhesus monkeys during exposure to prolonged restriction of motor activity

The objective of this investigation was to determine the effect of prolonged restriction of motor activity (hypokinesia [HK]) on several parameters of water metabolism in primates. The studies were performed on 12 rhesus monkeys aged 4–5 yr (5.10–6.85 kg) during the hypokinetic period of 90 d and during the prehypokinetic period of 30 d. They were divided into two equal groups: the first group was placed under ordinary vivarium conditions (vivarium control animals) and the second group was subjected to 90 d of HK (hypokinetic animals). For the simulation of the hypokinetic effect, the primates were immobilized on their abdomens in special tables. The legs of the monkeys were immobilized with hip and knee joints extended. The primates retained freedom of movement at elbow, wrist, and ankle. During the preexperimental period of 30 d and during the experimental period of 90 d, the following variables were determined: body weight, total body fluid content, specific total body fluid, mean fluid consumed and eliminated in urine, specific plasma resistance, hematocrit level, and plasma concentrations of sodium (Na) and potassium (K). In the hypokinetic primates, body weight decreased significantly when compared to the controls. Mean fluid intake, total body fluid, and specific total body fluid decreased, whereas mean daily fluid loss and specific mean daily fluid elimination increased significantly. Specific plasma resistance, hematocrit level, and plasma electrolyte concentrations increased significantly when compared to the control primates. It was concluded that prolonged restriction of motor activity induces significant changes in water metabolic parameters of primates leading in decreased total water content of the body.     

Assessment of motor function of the hand in aged rhesus monkeys

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.     

Observations of increased activity and tool use in captive rhesus monkeys exposed to troughs of water

This study investigated the effects of water troughs on nonhuman primates housed in a captive environment. Two groups of rhesus monkeys (Macaca mulatta) were exposed to water-filled troughs under three conditions: (1) standing water, (2) running water, and (3) a replication of standing and running water with novel objects. The effects of water exposure were assessed using a pretest phase (baseline), test phase (trough present), and posttest phase (baseline) design for each of the three conditions. Standing water produced different effects from running water. Monkeys were more active in the presence of standing water (higher levels of exploration and lower levels of social contact and grooming) than during baseline observations. In contrast, they were significantly more passive during the running water condition (higher levels of social contact) than baseline. Neither physical condition nor responses to dominance testing varied systematically over phases or between conditions. Tool use was observed during the standing water phases of Conditions 1 and 3. Three females from one group used a variety of cup-like containers as drinking utensils. A larger number of animals used the trough to soak chow prior to ingestion, and virtually all of the animals used the trough as a drinking source. These results suggest that exposure to water sources may elicit a broad spectrum of species-typical activity and may be a simple and inexpensive way to enrich the environment of captive rhesus monkeys. © 1993 Wiley-Liss, Inc.     

Extinction of rhesus monkeys (Macaca mulatto) in Xinglung,North China

An isolated population of rhesus monkeys living in Xinglung County, north of Beijing (latitude 40⪤gree N), was a natural population at the northernmost range of the species in Asia. Rhesus had been reported there at the end of the last century, based on a few specimens, but were not well known by zoologists until the beginning of the 1960s. The population remained approximately 50–60 individuals in the 1960s but then declined to only 4 or 5 monkeys about 5 years ago. It has been confirmed by local hunters and two recent field trips that the population is now probably extinct. As a result, the northern extent of the remaining natural range of the rhesus macaque in Asia has dropped 650 km southward to the Jiyuan Nature Reserve on the border of Hunan and Shanxi provinces, just north of the Yellow River.     

Behavioral effects of enrichment on pair-housed juvenile rhesus monkeys

Among captive primates, inanimate environmental enrichment can lead to measurable changes in behavior indicative of an improvement in psychological well-being. Although this has been demonstrated repeatedly for singly caged primates, the relationship is not as well studied for pairhoused animals. Study of the pair-housed setting has become increasingly relevant because of the social housing mandate of the Animal Welfare Act regulations. We therefore observed 68 juvenile rhesus monkeys born in 1988 and 1989 and living in mixed-sex pairs from the ages of 2 to 3 years. All pairs were compatible. Half of the pairs received two types of enrichment, while the remaining pairs served as controls. Enriched and control juvenile subjects differed in the amount of time that they spent being inactive, playing, and drinking, but did not differ in the amount of time they spent interacting with their partner. Grooming and play were the two most common socially directed activities in both groups, a species-appropriate pattern. Males played more and vocalized less than did females. Overall, enriched and control subjects spent equivalent amounts of time located within a social distance of one another, but there was some difference between groups in allocation of behaviors while near the pairmate. Environmental enhancers were frequently utilized, and led to relatively small changes in behavior between control and enriched subjects, suggesting that the presence of a partner for juvenile rhesus monkeys acts as a form of enrichment that may dilute the effects of inanimate environmental enhancements. © 1994 Wiley-Liss, Inc.     

Changes in hematology, biochemical values, and restraint ECG of rhesus monkeys (Macaca mulatta) following 6-month laboratory acclimation

The aim of this study was to determine if 6-month acclimation would enable accurate evaluation of hematological, biochemical data, and ECG recorded under restraint for conscious rhesus monkeys of both sexes. Periodic evaluation of these parameters was made during the 6-month period of acclimation. The platelet count, alkaline phosphatase, glucose, and sodium levels significantly decreased, whereas creatinine increased, compared with pre-acclimation values. The heart rate was significantly reduced compared with pre-acclimation values. QT-RR relation followed the square root regression function, which means modification of Bazett's QTc formula can be applied even if the ECG is recorded under restraint. In conclusion, 6-month acclimation was effective for stabilizing the blood data and for allowing accurate evaluation of the ECG even under restraint. Current results show that an acclimation period at least 3 months may be necessary prior to using rhesus monkeys for chronic studies.     

Effect of testosterone on epididymal proteins in castrated rhesus monkeys

The effect of testosterone on regulation of epididymal protein synthesis has been investigated in castrated rhesus monkeys (Macaca mulatta). The proteins in the treated monkeys were characterized using polyacrylamide gel electrophoresis (under nondenaturing and denaturing conditions) and electrofocusing. At least four distinct proteins have been shown to be synthesized by the monkey epididymis under testosterone influence. Two of these proteins were detected following two days of testosterone treatment while the other two proteins were detected after a six-day treatment period. None of these proteins was detectable in monkeys treated with estradiol for six days. Electrofocusing of epididymal cytosol proteins from untreated and testosterone-treated and castrated monkeys also confirmed the presence of four androgen-dependent proteins in this species. The isoelectric points of these proteins were shown to range between 5.8 and 6.4. The molecular weights of these proteins were found to vary between 47,500 and 66,000. The in vitro incorporation of ³H-labeled amino acids was markedly greater in the androgen-primed epididymis as compared with the control tissue.