The onset of puberty in colony-housed male and female titi monkeys (Plecturocebus cupreus): Possible effects of oxytocin treatment during peri-adolescent development.

Oxytocin has been used to treat neurodevelopmental conditions in adolescent patients but possible effects on reproductive development have not been well investigated. The effects of daily intra-nasal oxytocin treatment (12-18 months of age) on puberty and fertility were studied in colony-housed, male and female titi monkeys (Plecturocebus cupreus). Body weight, urinary conjugated pregnanes and estrogens (defining cyclicity) in females, and androgens and sperm in urine of in males, were measured from 1 to 3 years of age to detect puberty. Serum testosterone was also measured in males at 13, 23 and 33 months of age and hemi-castration at 3 years of age enabled assessment of testicular morphometry and oxytocin receptor expression. An oxytocin treatment*time interaction suggested a minor, transient suppression in weight gain after treatment ended. Note that females weighed 10% less across all ages. Oxytocin-treated females exhibited early, spurious ovulations but neither regular cyclicity (≈30 months) nor pregnancies were affected by treatment. Oxytocin did not affect the pubertal increase in urinary androgen or the first appearance of sperm, which occurred as early as 15 months of age. Treatment did delay the puberty-associated rise in serum testosterone in males. All males were pubertal by 22 months and all females by 32 months of age. Although no major male or female fertility outcome was observed, oxytocin demonstrated some physiological effects through a delay of testosterone secretion in males, induction of precocious ovulation in females, and a suppression of general weight gain for the months following treatment.

Social stability influences the association between adrenal responsiveness and hair cortisol concentrations in rhesus macaques.

Hair cortisol concentrations are increasingly being used in both humans and nonhuman animals as a biomarker of chronic stress. However, many details regarding how hair cortisol concentrations relate to the dynamic activity and regulation of the HPA axis are still unknown. The current study explores 1) how the regulation of the HPA axis in infancy relates to hair cortisol concentrations (HCC) in infancy 2) whether this relationship persists into adulthood under conditions of social stability, and 3) how social instability impacts these relationships. All subjects were rhesus monkeys housed in large social groups at the California National Primate Research Center, and all had participated in a 25-hr. long BioBehavioral Assessment (BBA) at 3-4 months of age when four plasma samples were taken to assess HPA regulation, in particular cortisol responses to 1) 2-hour social separation and relocation, 2) sustained challenge, 3) dexamethasone and 4) ACTH administration. In Study 1, hair samples were collected at the end of the BBA testing from 25 infant rhesus monkeys from 2 different stable social groups. In Study 2, hair samples were obtained at three timepoints from 108 adults from 3 different stable social groups (1 in the Spring/Summer and 2 in the Fall/Winter) to examine the temporal stability of the relationship between HCC and HPA axis regulation. In Study 3, subjects included 31 infants and 33 adults from a single social group experiencing social instability following the same procedures as in Studies 1 and 2. Generalized linear models were used to determine if infants' HPA axis activity and regulation predicted HCC in infancy (Study 1), in adulthood with animals living in stable social conditions (Study 2) or in animals living in an unstable social group (Study 3). Results indicated that for both infants and adults living in stable social groups, HCC are associated with the adrenal response to ACTH in infancy. Samples collected in the winter also had higher HCC than those collected in summer. In the unstable social group, adult hair cortisol levels were higher than in the stable social groups. Additionally, there were no consistent relationships between HCC and infant HPA axis regulation among adults or infants living in a group experiencing social instability. These results suggest that the aspects of the HPA axis that drive HCC may differ depending on context. Under stable, non-stressed conditions there seems to be a trait-like association between adrenal responsivity and HCC in infancy and adulthood. However, this association may be reduced or eliminated under conditions of social stress.

µ and κ opioid receptor distribution in the monogamous titi monkey (Callicebus cupreus): implications for social behavior and endocrine functioning.

The opioid system is involved in infant-mother bonds and adult-adult bonds in many species. We have previously shown that µ opioid receptors (MORs) and κ opioid receptors (KORs) are involved in regulating the adult attachment of the monogamous titi monkey. The present study sought to determine the distribution of MOR and KOR in the titi monkey brain using receptor autoradiography. We used [(3)H][D-Ala(2),N-Me-Phe(4),Gly(5)-ol]-enkephalin (DAMGO) to label MORs and [(3)H]U69,593 to label KORs. MOR binding was heterogeneous throughout the titi monkey brain. Specifically, MOR binding was observed in the cingulate gyrus (CG), striatum, septal regions, diagonal band, amygdala, hypothalamus, hippocampus, and thalamus. Binding was particularly dense in the septum, medial amygdala, paraventricular nucleus of the hypothalamus, mediodorsal thalamus with moderate binding in the nucleus accumbens. Consistent with other primate species, MOR were also observed in "neurochemically unique domains of the accumbens and putamen" (NUDAPs). In general KOR binding was more homogenous. KORs were primarily found in the CG, striatum, amygdala and hippocampus. Dense KOR binding was observed in the claustrum. Relative MOR and KOR binding in the titi monkey striatum was similar to other humans and primates, but was much lower compared to rodents. Relative MOR binding in the titi monkey hypothalamus was much greater than that found in rodents. This study was the first to examine MOR and KOR binding in a monogamous primate. The location of these receptors gives insight into where ligands may be acting to regulate social behavior and endocrine function.

The effects of morphine, naloxone, and κ opioid manipulation on endocrine functioning and social behavior in monogamous titi monkeys (Callicebus cupreus).

The µ opioid receptor (MOR) and κ opioid receptor (KOR) have been implicated in pair-bond formation and maintenance in socially monogamous species. Utilizing monogamous titi monkeys (Callicebus cupreus), the present study examined the potential role opioids play in modulating the response to separation, a potent challenge to the pair-bond. In Experiment 1, paired male titi monkeys were separated from their pair-mate for 30-min and then received saline, naloxone (1.0mg/kg), morphine (0.25mg/kg), or the KOR agonist, U50,488 (0.01, 0.03, or 0.1mg/kg) in a counter-balanced fashion, immediately prior to a 30-min reunion with their mate. Blood samples were collected immediately prior to and after the reunion. Males receiving morphine approached females less, initiated contact less, and females broke contact with the males less. The increase in cortisol in response to naloxone was greater compared to vehicle, and the increase in cortisol in response to the high dose of U50,488 compared to vehicle approached significance. In Experiment 2, paired males were treated with the KOR antagonist, GNTI (0.1, 0.3, or 1.0mg/kg), or saline 24h prior to a 60-min separation from their mate. Blood samples were collected at the time of injection and immediately before and after separation. Administration of the low dose of GNTI decreased the locomotor component of the separation response compared to vehicle. The present study found that the opioid system is involved in both the affiliative and separation distress components of a pair-bond, and these components are regulated by different opioid receptors.

Long-term exposure to intranasal oxytocin in a mouse autism model.

Oxytocin (OT) is a neuropeptide involved in mammalian social behavior. It is currently in clinical trials for the treatment of autism spectrum disorder (ASD). Previous studies in healthy rodents (prairie voles and C57BL/6J mice) have shown that there may be detrimental effects of long-term intranasal administration, raising the questions about safety and efficacy. To investigate the effects of OT on the aspects of ASD phenotype, we conducted the first study of chronic intranasal OT in a well-validated mouse model of autism, the BTBR T+ Itpr3tf/J inbred strain (BTBR), which displays low sociability and high repetitive behaviors. BTBR and C57BL/6J (B6) mice (N=94) were administered 0.8 IU/kg of OT intranasally, daily for 30 days, starting on day 21. We ran a well-characterized set of behavioral tasks relevant to diagnostic and associated symptoms of autism, including juvenile reciprocal social interactions, three-chambered social approach, open-field exploratory activity, repetitive self-grooming and fear-conditioned learning and memory, some during and some post treatment. Intranasal OT did not improve autism-relevant behaviors in BTBR, except for female sniffing in the three-chambered social interaction test. Male saline-treated BTBR mice showed increased interest in a novel mouse, both in chamber time and sniffing time, whereas OT-treated male BTBR mice showed a preference for the novel mouse in sniffing time only. No deleterious effects of OT were detected in either B6 or BTBR mice, except possibly for the lack of a preference for the novel mouse's chamber in OT-treated male BTBR mice. These results highlight the complexity inherent in understanding the effects of OT on behavior. Future investigations of chronic intranasal OT should include a wider dose range and early developmental time points in both healthy rodents and ASD models to affirm the efficacy and safety of OT.

A multivariate twin study of hippocampal volume, self-esteem and well-being in middle-aged men.

Self-esteem and well-being are important for successful aging, and some evidence suggests that self-esteem and well-being are associated with hippocampal volume, cognition and stress responsivity. Whereas most of this evidence is based on studies on older adults, we investigated self-esteem, well-being and hippocampal volume in 474 male middle-aged twins. Self-esteem was significantly positively correlated with hippocampal volume (0.09, P = 0.03 for left hippocampus, 0.10, P = 0.04 for right). Correlations for well-being were not significant (Ps > 0.05). There were strong phenotypic correlations between self-esteem and well-being (0.72, P < 0.001) and between left and right hippocampal volume (0.72, P < 0.001). In multivariate genetic analyses, a two-factor additive genetic and unique environmental (AE) model with well-being and self-esteem on one factor and left and right hippocampal volumes on the other factor fits the data better than Cholesky, independent pathway or common pathway models. The correlation between the two genetic factors was 0.12 (P = 0.03); the correlation between the environmental factors was 0.09 (P > 0.05). Our results indicate that largely different genetic and environmental factors underlie self-esteem and well-being on one hand and hippocampal volume on the other.

Intranasal vasopressin affects pair bonding and peripheral gene expression in male Callicebus cupreus.

Arginine vasopressin (AVP) is a neuropeptide hormone and neurotransmitter that has peripheral functions in water regulation, and central functions in the stress response and social bonding in male rodents. In this study, we investigated the role of AVP in partner preference behavior in a monogamous primate, the coppery titi monkey (Callicebus cupreus). Seven titi males each received three intranasal treatments: saline, low AVP (40 IU) and high AVP (80 IU) in random order, 1 week apart. They experienced a series of stimulus exposures to their female partner, a female stranger and an empty cage. Males were more likely to contact the stimulus and do so faster when either female stimulus was present. When pretreated with saline, males contacted the stranger more frequently than their partner; when pretreated with the high dosage of AVP, males contacted their partner more frequently than the stranger. We used microarray to measure peripheral changes in gene expression associated with intranasal AVP and found reduced expression of several genes coding for proinflammatory cytokines. The data presented here suggest that intranasally administered AVP has both central influences on social behavior and peripheral influences on inflammation in a nonhuman primate.

Plasma omega 3 polyunsaturated fatty acid status and monounsaturated fatty acids are altered by chronic social stress and predict endocrine responses to acute stress in titi monkeys.

Disturbances in fatty acid (FA) metabolism may link chronic psychological stress, endocrine responsiveness, and psychopathology. Therefore, lipid metabolome-wide responses and their relationships with endocrine (cortisol, insulin, and adiponectin) responsiveness to acute stress (AS) were assessed in a primate model of chronic social stress (CS). Compared to controls (not exposed to CS), CS increased (P≤0.05) circulating triacylglycerol (TG) and phosphatidylethanolamine (PE) n-6/n-3 and reduced (P≤0.05) cholesterol ester (CE) 16:1n7 and phosphatidylcholine (PC) 18:1n7, suggesting lower omega-3 FA status and stearoyl-CoA desaturase activity, respectively. Cortisol responses to AS positively correlated with TG n-6/n-3 (r=0.93; P=0.007), but only in CS monkeys. The adiponectin response to AS inversely correlated with CE n-6/n3 (r=-0.89; P=0.045) and positively with TG 16:1n7 (r=0.98; P=0.004), only in CS monkeys. Our results are consistent with previously reported FA profiles in stress-related psychopathology and suggest that compositional changes of specific lipid FAs may form new functional markers of chronic psychological stress.

Testosterone modifies the effect of APOE genotype on hippocampal volume in middle-aged men.

BACKGROUND: The APOE epsilon4 allele is an established risk factor for Alzheimer disease (AD), yet findings are mixed for how early its effects are manifest. One reason for the mixed results could be the presence of interaction effects with other AD risk factors. Increasing evidence indicates that testosterone may play a significant role in the development of AD. The aim of the present study was to examine the potential interaction of testosterone and APOE genotype with respect to hippocampal volume in middle age. METHODS: Participants were men from the Vietnam Era Twin Study of Aging (n = 375). The mean age was 55.9 years (range 51-59). Between-group comparisons were performed utilizing a hierarchical linear mixed model that adjusted for the nonindependence of twin data. RESULTS: A significant interaction was observed between testosterone and APOE genotype (epsilon4-negative vs epsilon4-positive). Those with both low testosterone (> or =1 SD below the mean) and an epsilon4-positive status had the smallest hippocampal volumes, although comparisons with normal testosterone groups were not significant. However, individuals with low testosterone and epsilon4-negative status had significantly larger hippocampal volumes relative to all other groups. A main effect of APOE genotype on hippocampal volume was observed, but only when the APOE-by-testosterone interaction was present. CONCLUSIONS: These findings demonstrate an interaction effect between testosterone and the APOE epsilon4 allele on hippocampal volume in middle-aged men, and they may suggest 2 low testosterone subgroups. Furthermore, these results allude to potential gene-gene interactions between APOE and either androgen receptor polymorphisms or genes associated with testosterone production.

Serotonin transporter expression is predicted by early life stress and is associated with disinhibited behavior in infant rhesus macaques.

Serotonin transporter (5-HTT) expression patterns may contribute to the risk for adverse psychological outcomes following early life stress. The present study investigated whether two types of early life stress, maternal and social aggression, and a serotonin transporter gene promoter polymorphism (rh5-HTTLPR) predicted lower post-stressor peripheral blood mononuclear cell (PBMC) 5-HTT expression in infant rhesus macaques. We further probed the relationships among these factors and infant behavioral disinhibition within a stressful situation. Fifty-three infants residing with mothers in large, complex social groups were observed over the first 12 postnatal weeks, during which time the rate of aggression received by the infant from their mothers and social group members was recorded. At 90-120 days of age, infants underwent a 25-h maternal separation/biobehavioral assessment, which included standardized behavioral assessments and blood sampling. Infants' rh5-HTTLPR genotypes were determined, and infant 5-HTT expression was quantified from PBMCs collected 8 h after separation. Receipt of aggression from the mother, but not from social group members, was associated with lower post-stressor 5-HTT expression. Lower post-stressor 5-HTT expression, but not receipt of aggression, was associated with disinhibited behavior during assessment. Rh5-HTTLPR genotype was unrelated to any measure. We conclude that 5-HTT regulation is linked with specific, presumably stressful early experiences in infant rhesus macaques. Further, 5-HTT expression predicted behavioral disinhibition, presumably via parallel processes that operate in the brain.

Examining cortisol rhythmicity and responsivity to stress in children with Tourette syndrome.

BACKGROUND: Tourette syndrome (TS) is characterized by motor and vocal tics, which are often exacerbated by stress. The hypothalamic-pituitary-adrenocortical (HPA) axis, a major stress response system is thus of interest for understanding TS. METHODS: Diurnal cortisol rhythms were estimated in medication-free children 7-13 years with TS (N=20) and healthy age-matched controls (N=16). Salivary samples were collected on 3 consecutive days from the home. HPA responsivity was assessed by examining cortisol in response to a mock and real MRI scan. RESULTS: The results of diurnal rhythmicity revealed a trend showing marginally lower evening cortisol for the TS group. By contrast, the TS group had higher cortisol levels in response to the stressor. There were strong, negative correlations between evening cortisol and tic severity as well as diurnal cortisol and anxiety. CONCLUSIONS: The children with TS showed increased cortisol in response to the MRI environment, supporting a model of enhanced HPA responsivity. The lower evening cortisol may be the result of chronic daily stress. Alternatively, the negative associations between cortisol and reported anxiety and tics may reflect biologically based anxiolytic properties of tic expression. Taken together, the results clearly implicate involvement of the HPA axis in the neuropathology of TS.

Dimensions of response to novelty are associated with social engagement and aggression in adult male rhesus macaques (Macaca mulatta).

In this study, the authors tested the hypothesis that behavioral response across social and nonsocial, novel and familiar conditions may be guided by the same trait(s) related to impulsivity in adult male rhesus macaques. The authors assessed 23 individuals' behavioral response to a series of nonsocial novel scenarios, as well as aggression and sociality within familiar and novel social contexts. Factor analysis of responses to nonsocial novelty identified two factors: Caution, which reflected latency to engage different novel situations, and Interest in Novelty, which consisted of duration and quality of exploration. Each dimension was associated with different social manifestations. Caution was negatively correlated with social aggression in novel and familiar social circumstances; Interest in Novelty was positively associated with social engagement in familiar, but not novel, social circumstances. The authors conclude that traits influencing impulsive response to novelty contribute to risky and normal social behavior across social contexts.

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.

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.

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.

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.

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.

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.

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.

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.