Hormonal response to restraint in rhesus monkeys

Abstract: The purpose of this study was to characterize the hormonal responses to a restraining system in four adult male rhesus monkeys (Macaca mulatta) in preparation for a spaceflight project. After the monkeys were accustomed to food and water (Phase I), blood-volume-regulating hormones were measured during three phases: 10 days in a metabolic cage (Phase II), 16 days sitting in a restrained position in a specially designed metabolism chair (Phase III) and 10 days in metabolic cage (Phase IV). An increase of active renin (30%) and vasopressin (25%) was observed at the end of Phase III. A decrease of atrial natriuretic peptide (ANP), urodilatin, and sodium excretion occurred during the first days of Phase III. Catecholamines were unchanged. A dramatic increase (tenfold) in urinary excretion of growth hormone occurred during all of Phase III and at the beginning of Phase IV. These findings are similar to those found in man during isolation inactivity and during confinement stress.     

Gastric secretion with feeding and restraint in conscious rhesus monkeys.

Four chair-housed rhesus monkeys (Macaca mulatta) were surgically prepared with vagally-innervated fundic gastric pouches. As in man, basal acid secretion was evident in all subjects. In response to a test meal, acid output rose twofold over basal values and remained elevated up to 6 h. Compared to control values, food-stimulated acid output was reduced significantly during periods of restraint.     

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 nonmaternal restraint on the vocalizations of infant rhesus monkeys (Macaca mulatta)

This study explored the effects of restraint by females other than the mother on the vocalizations of infant rhesus macaques (Macaca mulatta) in a captive social setting. In this species, females are very attracted to young infants and will frequently approach, groom, and hold the infant. Incompetent handling, abusive behavior, or extended periods away from the mother that prevent the infants from nursing represent potentially significant risks for infants. Vocal responses to such risky conditions appear to be the infants' only means to promote a return to their mothers. We examined the association between the severity of the threat posed to the infant and the nature of its vocal response to restraint, and whether the infants' calls influenced the behavior of their mothers or captors. The results suggest that situations posing greater risks for the infants, i.e., longer periods of restraint, were associated with a greater use of noisy screams. Furthermore, mothers' responding was associated with a greater use of noisy screams as well. The mothers' reactions, however, could be described as cautious, and consisted mostly of closer monitoring; such tempered response might be related to the risk of injury to the infant that could result from a more forceful and direct attempt at retrieval.     

Acute effects of marijuana smoke on complex operant behavior in rhesus monkeys

The acute behavioral effects of marijuana smoke were assessed in rhesus monkeys using a battery of food-reinforced complex operant tasks that included incremental repeated acquisition (IRA, n = 9), conditioned position responding (CPR, n = 8), progressive ratio (PR, n = 8), delayed matching to sample (DMTS, n = 6), and temporal response differentiation responding (TRD, n = 3). Marijuana or placebo smoke was delivered by a specialized face mask 15-min before sessions at exposure levels of 1, 5, 10, and 15 puffs (35cc/puff) or one cigarette smoked to a butt length of approximately 10 mm (approximately 20 puffs). Marijuana smoke caused significant disruptions of performance in all tests except PR after exposure to 10 or more puffs. Generally, response rates decreased or latencies to respond increased. Performance in the PR test was not consistently affected by marijuana exposure. Accuracy of responding was not altered by marijuana smoke at doses lower than those that decreased response rates in the IRA or CPR tests. In the three animals performing under all five schedules, the relative sensitivities for detecting marijuana behavioral effects were DMTS = TRD greater than IRA = CPR greater than PR. These results suggest that performance under operant schedules that are thought to represent some aspect of time perception, short-term memory, learning, motivation, and position discrimination show differential sensitivity to disruption by marijuana smoke, a finding similar to that noted previously for iv THC administration.     

Acute exposure of rhesus monkeys to DDT: Effect on carbohydrate metabolism

Four furocoumarins, two having a linear molecule, psoralen and 8-methylpsoralen and two having an angular molecule, angelicin and 4,5′-dimethylangelicin were tested for mutagenesis in Escherichia coli B wild type and in various strains deficient in known repair systems. The results indicate that both monoadducts and crosslinks are mutagenic. The mutagenic efficiency of the furocourmarins ranks in the following order 8-methylpsoralen > psoralen > angelicin > 4,5′-dimethylangelicin.     

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.     

Influence of restraint and ketamine anesthesia on adrenal steroids, progesterone, and gonadotropins in rhesus monkeys

Changes in gonadotropins, progesterone, cortisol, DHA, and DHAS were monitored in 10 female rhesus monkeys (Days 20-23 of the menstrual cycle) subjected to cage restraint with or without ketamine anesthesia for successive venipunctures. All animals were bled without sedation for 2 hr at 30-min intervals. Then 4 of the animals were anesthetized with ketamine-HCl and bleedings in all animals were continued for an additional 2.5 hr. FSH and progesterone were not appreciably affected by either restraint technique. LH declined steadily for the duration of the bleedings (P less than 0.05). Serum levels of cortisol and the adrenal androgens increased twofold (P less than 0.05). Anesthesia with ketamine had no effect on any of the six variables when compared with saline controls. Cortisol and dehydroepiandrosterone (DHA) levels tended to plateau (P less than 0.01) after 2 hr in both treated and control groups. In contrast, dehydroepiandrosterone sulfate (DHAS) levels increased continuously throughout the entire study period. These data indicate that ketamine anesthesia does not alter endocrine responses to venipuncture when administered following cage restraint of conscious animals. These findings further confirm the difficulties in obtaining estimates of basal levels of hormones which are responsive to stress and suggest that the first sample may provide the best estimate.     

Immunogenetic studies of rhesus monkeys

To assay for transplacental immunization in rhesus monkeys, sera from 253 postpartum females, 31 virgin females, and 40 males were tested for erythrocyte agglutinins. Nineteen percent of the mothers exhibited antibodies, but less than three percent of the virgin females or males did so. Antibodies were detected in 26 percent of the mothers who bore blood group-incompatible infants, in contrast to only eight percent of the mothers with compatible offspring. Thus, blood group incompatibility may lead to transplacental alloimmunization of the rhesus female. Unlike the situation in humans, hemolytic disease was not observed, even when the erythrocytes of the newborn rhesus were coated with maternal antibodies.     

Immunogenetic studies of rhesus monkeys

Five alloimmune rhesus monkey blood typing reagents have been produced which define two new blood group loci inMacaca mulatto. Three of these reagents detect blood group factors at theM locus; the other two detect factors at theN locus. By typing over 1900 pedigreed monkeys we have established that these two loci are independent of each other and of any of our previously defined blood group systems.     

Generation of chimeric rhesus monkeys

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

Menopause in female rhesus monkeys

Fifteen female rhesus monkeys (Macaca mulatto), ranging in age from 8 to 34 years, were studied for one year to characterize the endocrine and menstrual changes associated with menopause in this species. Five monkeys were premenopausal; these younger monkeys, ages 8–11 years, menstruated and showed cyclic ovarian activity during the 12–month study period, as evidenced by menses and periodic elevations of serum estradiol (E₂) and luteinizing hormone (LH) concentrations. Four females, ages 24–26 years, were in transition to menopause. Two of these perimenopausal females menstruated and secreted E₂ and LH in a periodic fashion; the other two females showed elevated LH concentrations, consistently low E₂ levels, and no evidence of menstruation. Six females, ages 27–34 years, were clearly postmenopausal; LH concentrations were high, whereas E₂ concentrations were uniformly low. There was a significant inverse correlation between basal E₂ concentrations and age, and a significant positive correlation between age and LH concentrations across all 15 animals. Hormonal changes indicative of ovulation, when they occurred, were generally restricted to the winter and early spring months. Histological analysis of ovaries from four postmenopausal females revealed little or no evidence of active folliculogenesis. These data indicate that menopause in female rhesus monkeys does not occur until the second half of thethird decade of life. © 1995 Wiley-Liss, Inc.     

Preference patterns for skewed gambles in rhesus monkeys

While standard models of risky choice account for the first and second statistical moments of reward outcome distributions (mean and variance, respectively), they often ignore the third moment, skewness. Determining a decision-maker''s attitude about skewness is useful because it can help constrain process models of the mental steps involved in risky choice. We measured three rhesus monkeys’ preferences for gambles whose outcome distributions had almost identical means and variances but differed in skewness. We tested five distributions of skewness: strong negative, weak negative, normal, weak positive and strong positive. Monkeys preferred positively skewed gambles to negatively skewed ones and preferred strongly skewed and normal (i.e. unskewed) gambles to weakly skewed ones. This pattern of preferences cannot be explained solely by monotonic deformations of the utility curve or any other popular single account, but can be accounted for by multiple interacting factors.