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Biomedical subjects

S P Mendoza

Publications and source records attributed to S P Mendoza.

At least 19 recordsLinked to original sources

Behavioral and physiological adaptation to repeated chair restraint in rhesus macaques.

Physical restraint is a commonly used procedure when working closely with nonhuman primates. Nonhuman primates show rapid behavioral changes when learning the restraint procedure, and these changes have been taken to reflect behavioral and physiological habituation to the procedure. This study examined the behavioral and adrenocortical responses to repeated physical restraint in a large sample of adult male rhesus monkeys. Subjects showed a decline in behavioral agitation and cortisol concentrations across seven consecutive days of restraint. The changes in adrenocortical responsiveness were also coincident with an increased sensitivity to dexamethasone and a change in early morning basal cortisol secretion. The subjects were restrained for a single session 6 months later, and while the reduction in behavioral agitation was still present, the majority of changes in adrenocortical responsiveness were no longer present. These data show that behavior is not necessarily an indicator of underlying physiological processes and that the reduction of hypothalamic-pituitary-adrenal (HPA) activity with repeated restraint is due to physiological adaptation to high glucocorticoid concentrations and not to psychological habituation to the restraint procedures.

Adaptation, Physiological↗

Are subordinates always stressed? A comparative analysis of rank differences in cortisol levels among primates.

Among primate species there is pronounced variation in the relationship between social status and measures of stress physiology. An informal meta-analysis was designed to investigate the basis of this diversity across different primate societies. Species were included only if a substantial amount of published information was available regarding both social behavior and rank-related differences in stress physiology. Four Old World and three New World species met these criteria, including societies varying from small-group, singular cooperative breeders (common marmoset and cotton top tamarin) to large-troop, multi-male, multi-female polygynous mating systems (rhesus, cynomolgus, talapoin, squirrel monkeys, and olive baboon). A questionnaire was formulated to obtain information necessary to characterize the stress milieu for individuals in particular primate societies. We standardized cortisol values within each species by calculating the ratio of basal cortisol concentrations of subordinates to those of dominants in stable dominance hierarchies and expressing the ratio as a percentage (relative cortisol levels). The meta-analysis identified two variables that significantly predicted relative cortisol levels: subordinates exhibited higher relative cortisol levels when they (1). were subjected to higher rates of stressors, and (2). experienced decreased opportunities for social (including close kin) support. These findings have important implications for understanding the different physiological consequences of dominant and subordinate social status across primate societies and how social rank may differ in its behavioral and physiological manifestations among primate societies.

Aggression↗

Cortisol responses to immobilization with Telazol or ketamine in baboons (Papio cynocephalus/anubis) and rhesus macaques (Macaca mulatta).

Little is known about the influence of Telazol on cortisol or of anesthetic agents on immunological measures, and reports of ketamine's effect on cortisol are inconsistent. We measured effects of Telazol, ketamine and blood sampling on cortisol in male rhesus macaques and male savannah baboons. We also obtained leukocyte counts in the macaques. In macaques, Telazol reduced cortisol in the morning but not in the afternoon; ketamine had no effect on cortisol in these animals. In baboons, cortisol changed little post-Telazol but increased post-ketamine. In macaques, lymphocyte numbers decreased following afternoon injection of Telazol, ketamine or saline. The injection and blood sampling process increased cortisol levels in monkeys not trained to extend an arm but exerted no effect on cortisol in trained macaques. Thus, the animals' physiological responses to blood sampling and immobilization are influenced by such variables as anesthetic agent, species, time of day, and familiarity with the blood sampling process.

Anesthetics, Dissociative↗

Excretion and measurement of estradiol and progesterone metabolites in the feces and urine of female squirrel monkeys (Saimiri sciureus).

The first objective of the present study was to determine the metabolic form and rate of excretion of ovarian hormone metabolites in the urine and feces of female squirrel monkeys injected with radiolabeled progesterone (Po) and estradiol. The major portion of the urinary metabolites of both hormones was excreted within 16-24 hr post-injection. Estrogen and Po isotopes in feces exhibited an excretion peak at 16 hr post-injection. The majority of recovered radiolabel of both hormones was excreted in feces. Chromatographic separation of fecal extractions indicated that the major estrogen metabolites in feces are in the free as opposed to the conjugated form. The radioactivity and immunoreactivity for estrone and estradiol (E(1) and E(2), respectively) in eluates of fecal samples subjected to celite co-chromatography indicated that both free E(1) and E(2) exist as excretion products in the feces of female squirrel monkeys. The major radioactive peaks for Po metabolites showed peaks in the elution profile at or very near the Po standard, and corresponded with the celite co-chromatography elution profile of Po standard when subjected to enzyme immunoassay (EIA). The second objective was to validate the application of EIA systems to measure fecal metabolites. Reproductive events of one female squirrel monkey across one annual reproductive cycle are described using the endocrine profile generated from fecal steroid assays. Examination of this profile confirmed that longitudinal fecal sampling and steroid hormone metabolite measurement in feces was not only feasible and practical, but accurately detected known reproductive events as well.

Animals↗

Developmental changes in responsiveness to parents and unfamiliar adults in a monogamous monkey (Callicebus moloch).

Titi monkeys (Callicebus moloch) are monogamous New World primates that are characteristically found in family-type groups consisting of a mated adult pair and one or two young. The factors maintaining the small size of these groups are not known. Based on observations of free-ranging and captive families, parental aggression toward older offspring seems unlikely to play a significant role. Maturing individuals themselves, however, could undergo behavioral changes that weaken ties to their natal group. These might include waning of affiliative relations with parents, or subtle forms of aversion. Independent of such changes, increasing interest in unfamiliar conspecifics could be a factor. We examined these possibilities in the present study by assessing changes in social behavior and social preferences from initial ambulatory independence (6 months) through reproductive maturity (24 months) in a combined cross-sectional/longitudinal study of 21 captive titi monkeys living with their parents. Responses to both parents and to an unfamiliar adult heterosexual pair, a single unfamiliar adult male, and a single unfamiliar adult female were observed when subjects were given a choice between parents and strangers presented simultaneously or as the only social incentive. Social stimuli were at opposite ends of a 16.8-m-long test corridor. Subjects could move freely about the corridor for 5 min with each configuration of social stimuli. They stayed closer to parents than to strangers at all ages. Responsiveness to strangers increased with age and suggested growing ambivalence, particularly toward the male stranger. As they approached 24 months of age, male subjects showed a dramatic increase in the frequency and intensity of agonistic behaviors toward male strangers, behaviors that were rarely directed toward female strangers or parents. Waning of attraction to parents may be less important in dispersal from the natal group than changing reactions to strangers.

Aggression↗

Increased social fear and decreased fear of objects in monkeys with neonatal amygdala lesions.

The amygdala has been implicated in the mediation of emotional and species-specific social behavior (Kling et al., 1970; Kling and Brothers, 1992; Kluver and Bucy, 1939; Rosvold et al., 1954). Humans with bilateral amygdala damage are impaired in judging negative emotion in facial expressions and making accurate judgements of trustworthiness (Adolphs et al., 1998, 1994). Amygdala dysfunction has also been implicated in human disorders ranging from social anxiety (Birbaumer et al., 1998) to depression (Drevets, 2000) to autism (Bachevalier, 1994; Baron-Cohen et al., 2000; Bauman and Kemper, 1993). We produced selective amygdala lesions in 2-week-old macaque monkeys who were returned to their mothers for rearing. At 6-8 months of age, the lesioned animals demonstrated less fear of novel objects such as rubber snakes than age-matched controls. However, they displayed substantially more fear behavior than controls during dyadic social interactions. These results suggest that neonatal amygdala lesions dissociate a system that mediates social fear from one that mediates fear of inanimate objects. Furthermore, much of the age-appropriate repertoire of social behavior was present in amygdala-lesioned infants indicating that these lesions do not produce autistic-like behavior in monkeys. Finally, amygdala lesions early in development have different effects on social behavior than lesions produced in adulthood.

Aging↗

The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta).

The role of the amygdala in dyadic social interactions of adult rhesus monkeys (Macaca mulatta) was assessed after bilateral ibotenic acid lesions. Social, nonsocial, and spatial behaviors of amygdalectomized and control monkeys were assessed in 3 dyadic experiments: constrained, unconstrained, and round robin. Lesions produced extensive bilateral damage to the amygdala. Across all experiments, the amygdalectomized monkeys demonstrated increased social affiliation, decreased anxiety, and increased confidence compared with control monkeys, particularly during early encounters. Normal subjects also demonstrated increased social affiliation toward the amygdalectomized subjects. These results indicate that amygdala lesions in adult monkeys lead to a decrease in the species-normal reluctance to immediately engage a novel conspecific in social behavior. The altered behavior of the amygdalectomized monkeys may have induced the increased social interactions from their normal companions. This is contrary to the idea that amygdalectomy produces a decrease in social interaction and increased aggression from conspecifics.

Aggression↗

Annual physiological changes in individually housed squirrel monkeys (Saimiri sciureus).

This study investigated whether annual changes in physiology occur in individually housed squirrel monkeys (Saimiri sciureus). Physiological measures were monitored for 20 months. Over the course of the study, all individually housed males and females exhibited clear annual changes in gonadal and adrenal hormone levels, and males exhibited species-typical changes in body weight. Females exhibited a typical pattern of hormonal changes, with elevations in gonadal steroids occurring during the same months as elevations in cortisol. Males, however, exhibited an atypical pattern, as elevations in hormone levels were not synchronized with each other; rather, elevations in testosterone occurred out of phase with changes in cortisol and body weight. The timing of annual events in individually housed subjects was compared to that in nearby social groups, in which the timing of the breeding season from year to year was determined by social group formations and was outside the naturally occurring breeding season. Elevations of ovarian and adrenocortical hormones in individually housed females were synchronized with indices of breeding in heterosexual social groups. Similarly, weight gain in males was associated with elevations in cortisol and, as with socially housed males, tended to precede seasonal breeding in the social groups. In contrast, annual testosterone elevations for individually housed males were not synchronized with breeding in nearby social groups. We conclude that direct physical interaction is not required for the annual expression of breeding readiness. Synchrony of seasonality among squirrel monkeys may be accomplished by distant social cues in females, but males may require physical interaction for complete synchrony of annual physiological changes.

Adrenal Cortex Hormones↗

Reproductive biology of female titi monkeys (Callicebus moloch) in captivity.

Titi monkeys (Callicebus spp., Cebidae) are monogamous neotropical primates that live in family-like groups typically consisting of an adult monogamous pair and one or two young. Knowledge about the reproductive biology of this genus is scanty. This study investigated the reproductive biology of female dusky titi monkeys (Callicebus moloch). An initial analysis characterized reproductive parameters of 32 females from a captive colony maintained for 23 years at the California Regional Primate Research Center (CRPRC). The colony records provided data on reproductive parameters such as interbirth intervals, seasonality, age at first pregnancy, and reproductive rate in captivity. Changes in urinary levels of estrone conjugates (E1C) and pregnanediol-3alpha-glucuronide (PdG) were used to characterize major reproductive events. Urine samples from eleven females were collected during 17 months. The endocrine data were used to examine changes associated with cycling, conception, and the post-partum period as well as to determine the duration of the ovarian cycle and gestation length. The analysis of colony records indicated that females whose infant survived through weaning gave birth at intervals remarkably close to one year, while those who lost their offspring showed a significantly shorter interval. As long as they lived within the family group, mature female offspring did not breed. The analysis of the endocrine profiles indicated that after giving birth to a viable offspring, females undergo a relatively prolonged period of anovulation (approx. 6.5 months), followed by 1-3 non-conceptive cycles (approx. 1 month), after which they conceive and gestate (4.3 months).

Animals↗

The relationship of personality dimensions in adult male rhesus macaques to progression of simian immunodeficiency virus disease.

Studies of nonhuman primate personality have suggested that physiological correlates of relevant behavioral dimensions exist. The present study examined personality using techniques similar to those employed in human personality research. Adult male rhesus monkeys were each rated on 25 adjectives while living in their natal groups. Approximately 1.5 years later, 18 animals were inoculated with the simian immunodeficiency virus (SIV) and exposed to socially stable or socially unstable conditions. Behavior, viral load (SIV RNA), plasma cortisol concentrations, and the IgG response to SIV and to rhesus cytomegalovirus were measured at regular intervals. Multiple regression analyses revealed that the four personality dimensions (Sociability, Confidence, Equability, Excitability) were correlated with various measures. Following inoculation with SIV, animals higher in Sociability showed a more rapid decline in plasma cortisol concentrations, elevations in the anti-RhCMV IgG response, and a decline in SIV RNA. The results indicate that personality factors in rhesus monkeys do have physiological correlates that have significance for disease processes and that in the context of a social manipulation, Sociability, reflecting the tendency to engage in affiliative interactions, is an important factor in explaining outcome measures at early time points.

Animals↗

Social stress results in altered glucocorticoid regulation and shorter survival in simian acquired immune deficiency syndrome.

From early in the AIDS epidemic, psychosocial stressors have been proposed as contributors to the variation in disease course. To test this hypothesis, rhesus macaques were assigned to stable or unstable social conditions and were inoculated with the simian immunodeficiency virus. Animals in the unstable condition displayed more agonism and less affiliation, shorter survival, and lower basal concentrations of plasma cortisol compared with stable animals. Early after inoculation, but before the emergence of group differences in cortisol levels, animals receiving social threats had higher concentrations of simian immunodeficiency virus RNA in plasma, and those engaging in affiliation had lower concentrations. The results indicate that social factors can have a significant impact on the course of immunodeficiency disease. Socially induced changes in pituitary-adrenal hormones may be one mechanism mediating this relationship.

Acquired Immunodeficiency Syndrome↗

Individual differences in peripheral blood immunological and hormonal measures in adult male rhesus macaques (Macaca mulatta): evidence for temporal and situational consistency.

A growing body of research has indicated that consistent individual differences exist in physiological systems with which the immune system interacts. Few data have been reported that demonstrate stable individual differences in immunological measures, however. In the present study, enumerative measures of immune system activity were examined in 36 adult male rhesus macaques over a 13 month period under baseline conditions as well as under conditions of pharmacological and physical challenge. Blood samples were assayed for plasma concentrations of ACTH and cortisol, as well as neutrophil, total lymphocyte, CD4+ and CD8+ lymphocyte numbers, and the CD4/CD8 ratio. Analyses revealed that individual differences in the CD4/CD8 ratio and, to a lesser extent, plasma ACTH and cortisol concentrations, and neutrophil and CD4+ lymphocyte numbers were consistent across situations and times, despite changes in mean values during the various blood sampling sessions. The results suggest that the CD4/CD8 ratio might be considered trait-like and a useful immunological measure of biobehavioral organization.

Adrenocorticotropic Hormone↗

Generic aspects of primate attachments: parents, offspring and mates.

We examine behavioral and physiological aspects of primate emotional attachments in the context of four relationships: infant-to-parent, parent-to-infant, and adult male-to-female and adult female-to-male in a monogamous New World species. Emotional attachments in each of these relationships show striking similarities at a basic functional level. The nature of these similarities suggests that they are produced by the same psychoneuroendocrine core, which appears to be present in all mammals. We also consider the development of each of kind of attachment. In contrast to fundamental similarities in the expression of attachment, their development in each case appears to be based on distinct, species-typical dispositions and constraints.

Adult↗

Cytomegalovirus and simian immunodeficiency virus coinfection: longitudinal study of antibody responses and disease progression.

Antibody titers to rhesus cytomegalovirus (RhCMV) were prospectively analyzed over a period of 68 weeks in a longitudinal serosurvey of 17 RhCMV-seropositive rhesus macaques (Macaca mulatta) experimentally coinfected with simian immunodeficiency virus (SIV). These were compared with anti-RhCMV titers in 18 animals that were also naturally infected with RhCMV but not infected with SIV. Fluctuations in anti-RhCMV antibody titers were observed within 5 weeks of SIV inoculation, and two distinct patterns of RhCMV antibody response were observed in SIV-infected animals. Animals showing a progressive decline in anti-RhCMV immunoglobulin G (IgG) exhibited the most rapid disease progression, coincident with low anti-SIV and anti-tetanus toxoid IgG responses, high levels of p27 antigen in the plasma, and short survival. Animals exhibiting a more stable CMV-specific response after SIV inoculation had the least rapid disease course. Anti-RhCMV antibody titers in SIV-uninfected animals remained relatively stable during the period of study. Evidence that preinoculation immunologic measures predicted postinoculation outcome was equivocal.

Animals↗

Effects of duration of separation on responses to mates and strangers in the monogamous titi monkey (Callicebus moloch).

Adult male and female titi monkeys form an intense social bond characterized by high levels of affiliative interactions between pairmates and agonistic responses to strangers. In natural settings, separation between mates can vary from brief periods, as when mates drift apart during feeding, to permanent separation, occasioned by desertion or death. In this study we asked how different durations of separation altered the behavior of male and female titi monkeys (Callicebus moloch). We compared the effects of brief separation such as might occur incidentally during feeding (1-2 h) with prolonged separation such as might occur if one partner died or deserted (5 days). Effects were observed during a 30 min reunion of pairmates or during a 30 min encounter with a stranger of the opposite sex. Following brief separation, interactions between mates and between strangers clearly differed in measures of affiliation, but not in behaviors indicative of arousal. Following prolonged separation, measures of arousal increased with both mated pairs and strangers. Females tended to interact more readily with a stranger following prolonged separation than after brief separation, but interactions between mates were essentially unchanged and differed substantially from those between strangers. The data suggest that the pair bond persists in titi monkeys after prolonged social isolation, despite increased interest in interacting with potential new partners.

Animals↗

Autonomic balance in Saimiri sciureus and Callicebus moloch: relation to life-style.

Previous research has shown heart rate to be substantially higher in squirrel monkeys (Saimiri sciureus) than titi monkeys (Callicebus moloch). In order to evaluate whether species differences in heart rate can be accounted for by contrasting patterns of autonomic activity, heart rate in response to novel test conditions was compared using standard pharmacological agents that selectively block the sympathetic (propranolol) or parasympathetic (atropine) components of the autonomic nervous system. Squirrel monkeys were found to exhibit greater sympathetic response to novelty than titi monkeys. In contrast, sympathetic activity in titi monkeys, but not squirrel monkeys, was quickly counteracted by a strong parasympathetic response. Intrinsic heart rates, estimated by blocking both parasympathetic and sympathetic input to the heart, were within the ranges of values predicted by body weight. Heart rate for titi monkeys stabilizes at intrinsic heart rate, whereas heart rate for squirrel monkeys is maintained well above intrinsic heart rate in a novel environment. The contrast between species in autonomic balance is consistent with and probably contributes to each species characteristic mode of interacting with their social and non-social environment.

Analysis of Variance↗

Seasonality in squirrel monkeys (Saimiri sciureus): social facilitation by females.

The extent to which social living arrangements influenced seasonal changes in physiology and behavior was examined in adult squirrel monkeys (Saimiri sciureus). Data were collected over 20 months (encompassing two breeding seasons) from animals that were housed in three mixed-sex social configurations that varied in the number of heterosexual and isosexual social partners. For both sexes, the presence of multiple females was found to facilitate reproduction. Females housed with other females were more likely to exhibit seasonal ovarian cyclicity and tended to have higher conception rates. Social facilitation of reproduction was particularly prominent for subordinate females. The presence of same-sex companions also resulted in reduced adrenocortical output in females during the first nonbreeding season. In males, the availability of multiple females increased plasma testosterone levels, except in the presence of more dominant males. Seasonal increases in male weight coincided with increased cortisol levels and were most prominent in social groups containing multiple females. The influence of multiple females on male seasonality occurred despite the finding that male-female interactions were infrequent and, in fact, occurred less frequently when isosexual partners were available. Unexpectedly, affiliative social interactions between same-sex and opposite-sex partners occurred less frequently during the breeding season. As expected, behaviors associated with sex tended to increase during the breeding season. Very little agonism was observed during the course of the study and there was no evidence of interanimal competition for mates.

Animals↗