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Studies of handedness suggest a relationship between hemispheric specialisation and emotional processing. Recently measures of lateralised tympanic membrane temperature (TMT) have identified similar relationships (i.e., the left hemisphere is involved in approach behaviour and the right hemisphere avoidance behaviour). In the present study we examined lateralised changes in TMT in response to social interaction in 10 Garnett's bushbabies. Additionally, we examined whether handedness could be used as a predictor of approach-avoidance tendencies. We found a positive association between temperature change and both allogrooming and affiliative approach. Social behaviour did not differ between right- and left-handed bushbabies. These findings are discussed in terms of existing theories of asymmetric emotional processing. Overall, the data suggest that there is a left hemisphere specialisation for processing approach-related behaviours, which is consistent with existing models of lateralised emotional processing. Our data also indicate that TMT is a reliable, cost-effective measure of cerebral activation that is less invasive and more practical than alternative measures such as EEG, PET, and fMRI.

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BACKGROUND: The human apolipoprotein E (APOE) gene is polymorphic, with three primary alleles (E2, E3, E4) that differ at two key non-synonymous sites. These alleles are functionally different in how they bind to lipoproteins, and this genetic variation is associated with phenotypic variation for several medical traits, including cholesterol levels, cardiovascular health, Alzheimer's disease risk, and longevity. The relative frequencies of these alleles vary across human populations, and the evolution and maintenance of this diversity is much debated. Previous studies comparing human and chimpanzee APOE sequences found that the chimpanzee sequence is most similar to the human E4 allele, although the resulting chimpanzee protein might function like the protein coded for by the human E3 allele. However, these studies have used sequence data from a single chimpanzee and do not consider whether chimpanzees, like humans, show intra-specific and subspecific variation at this locus. METHODOLOGY AND PRINCIPAL FINDINGS: To examine potential intraspecific variation, we sequenced the APOE gene of 32 chimpanzees. This sample included 20 captive individuals representing the western subspecies (P. troglodytes verus) and 12 wild individuals representing the eastern subspecies (P. t. schweinfurthii). Variation in our resulting sequences was limited to one non-coding, intronic SNP, which showed fixed differences between the two subspecies. We also compared APOE sequences for all available ape genera and fossil hominins. The bonobo APOE protein is identical to that of the chimpanzee, and the Denisovan APOE exhibits all four human-specific, non-synonymous changes and appears functionally similar to the human E4 allele. CONCLUSIONS: We found no coding variation within and between chimpanzee populations, suggesting that the maintenance of functionally diverse APOE polymorphisms is a unique feature of human evolution.

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PURPOSE: Combination estrogen + progestin therapy has been associated with increased breast cancer risk in postmenopausal women. Selective estrogen receptor modulators (SERM) are potential alternatives to progestins, although the endometrial safety of estrogen + SERM co-therapies is not known. The goal of this study was to evaluate the endometrial profile of low-dose estradiol and the SERM tamoxifen alone and in combination. EXPERIMENTAL DESIGN: Twenty-four postmenopausal female cynomolgus macaques were randomized by social group to receive placebo, low-dose micronized estradiol (E(2); 0.25 mg/1,800 kcal), the SERM tamoxifen (Tam; 20 mg/1,800 kcal), or E(2) + Tam for 4 months in a parallel-arm design. RESULTS: Tamoxifen alone resulted in overlapping but distinct effects compared with E(2). Both E(2) and Tam increased uterine weight and endometrial thickness, whereas only E(2) increased endometrial proliferation. Morphologic effects were similar for Tam and E(2) + Tam, which both induced stromal fibrosis and cystic change. Tamoxifen inhibited E(2)-induced proliferation and expression of genes related to cell cycle progression while exhibiting mixed agonist and antagonist effects on gene markers of estrogen receptor activity. The gene expression profile for E(2) + Tam was distinct from either E(2) or Tam alone but dominated by the Tam effect for estrogen-regulated genes. Tam also attenuated E(2) effects on both vaginal maturation and cervical epithelial height. CONCLUSIONS: These findings characterize a novel phenotype resulting from estrogen + SERM co-therapy. The predominance of Tam effects on endometrial proliferation, morphology, and transcriptional profiles suggests that endometrial risks for E(2) + Tam may be similar to Tam alone.

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The short-term effects on rates and durations of self-injurious behavior and self-directed stereotypies associated with various doses of fluoxetine (FLX) and venlafaxine (VEN) were examined in rhesus macaques. Adult male macaques (Macaca mulatta; n = 17; age, 7 to 15 y) with at least 1 episode of severe SIB within the past 5 y were randomized to treatment with FLX (n = 6), VEN (n = 6), or placebo (PLC, n = 5), administered by voluntary consumption of medication provided in fruit-flavored tablets. After 4-wk baseline and 4-wk placebo lead-in phases, doses were increased monthly for 4 mo (FLX: 0.5, 2.0, 4.0, and 8.0 mg/kg; VEN: 2.0, 4.0, 8.0, and 16.0 mg/kg). Animals in the PLC condition received similar nonmedicated fruit-flavored tablets. Focal behavioral observations, plasma drug levels, and neurochemical data were obtained. Results indicated that rates and percentage time spent self-biting declined at all doses of FLX, with the greatest effect seen at 2.0 mg/kg. For VEN, percentage time spent self-biting was significantly lower only at the 4.0 mg/kg dose. Treatment-induced reductions in platelet serotonin and cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5HIAA) concentrations were substantially greater in the FLX-treated condition than in the VEN-treated condition. Plasma FLX and norfluoxetine levels increased with FLX dose; plasma levels of VEN were low and not dose-related. Fluoxetine at a dose of 2.0 mg/kg daily was most efficacious in reducing SIB, and the observed reductions in platelet serotonin and CSF 5HIAA levels indicated substantial bioeffect at this dose. Treatment with VEN was marked by noncompliance, low bioeffect, and low efficacy.

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Self-injurious behavior (SIB) among captive primates is a recurring problem for those who manage such facilities. Its prevalence highlights the need for research evaluating the effectiveness of potential treatment approaches. In the present study, 4 wk of dietary supplementation with L-tryptophan (100 mg daily) was evaluated for the treatment of self-inflicted wounds in 22 small-eared bushbabies, a prosimian primate, with a history of SIB. The treatment significantly reduced stereotypy and was associated with a reduction in wound area and severity. In terms of physiologic measures, preexisting high levels of cortisol were reduced in bushbabies with SIB, whereas serotonin concentrations were increased after 4 wk of treatment. Results indicate that L-tryptophan as a dietary supplement may be a viable adjunct to standard husbandry procedures for animals exhibiting maladaptive behaviors such as stereotypy and SIB.

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Research suggests that auditory environmental enrichment might reduce abnormal behavior in certain primate species. The authors evaluated the behavioral effects of exposure to music in a prosimian primate (Garnett's bushbaby; Otolemur garnettii). They exposed bushbabies to a Mozart concerto for 15 min per day for 20 d (5 h exposure total), video-recorded them and subsequently analyzed the frequency of subjects' grooming and stereotypic behaviors. The authors compared the data with baseline behavioral data that had been recorded over a 20-d period before the experimental treatment. Neither stereotypy nor grooming behavior varied as a result of exposure to music. These results do not support the hypothesis that auditory enrichment in the form of exposure to music is an effective means of reducing stereotypic behavior in O. garnettii.

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We examined the effects of outdoor housing on self-injurious and stereotypic behavior in adult male rhesus macaques with a history of self-wounding that were previously singly housed indoors for at least 4 y prior to the study. Baseline behavioral observations were collected over 2.5 mo. In phase 1, animals were relocated outdoors in 1 of 2 experimental conditions, group-housed (n = 8) or single-housed (n = 5), for 6 wk. In phase 2, group-housed animals were observed outdoors for an additional 6 wk. Behavioral observations were done using focal sampling techniques. In phase 1, rates of self-biting and self-directed stereotypies and time spent displaying idiosyncratic self-directed stereotypies decreased significantly when group- and single-housed animals were housed outdoors. Rates of yawning and scratching were significantly decreased for group- and single-housed animals and, for group-housed animals, self-grooming decreased with outdoor housing. In phase 2, rates of self-biting, time engaging in idiosyncratic self-directed stereotypies, and yawning remained significantly lower during weeks 7 through 12 (outdoor housing) compared with those under indoor housing. Rates of scratching and time spent self-grooming decreased significantly during the first 6 wk but then returned to baseline levels. Our findings suggest that self-biting and self-directed stereotypic behavior in rhesus macaques with a history of self-injurious behavior is significantly reduced by outdoor housing regardless of whether animals are socially or individually housed.

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The unanticipated underutilization of chimpanzees (Pan troglodytes) by the National Institutes of Health (NIH) for current NIH-supported research has prompted the application of a variety of contraceptive forms. Among the many methods attempted, the intrauterine device (IUD) has been described as having an efficacy similar to that described for humans. In addition, the device is both a financially sound and practical solution to prevention of overpopulation, while minimizing disruption of normal cyclic hormonal fluctuations. However, variations in the size and shape of the sexual skin of the female chimpanzee and the depth of the vaginal vault have posed physical constraints on the use of instrumentation developed for humans for assisting with insertion of the device. In addition the literature is lacking in specific methodology for pelvic examination in chimpanzees. Previously, the University of Louisiana at Lafayette New Iberia Research Center used a 3-ml plastic syringe case as a vaginal speculum to accommodate requirements of an approved research protocol in African green monkeys (Chlorocebus aethiops). Similarly, a simple and effective disposable vaginal speculum was developed for the chimpanzee. The closed tip of a plastic syringe case of appropriate size (20 to 60 ml) was removed to provide an open tube; momentary heating smoothed the cut edge. This simple speculum allowed for sufficient visualization of the cervix for assessment and assistance in the insertion of the IUD. Variously sized speculums were prepared to accommodate differences in animal size. This simple and effective speculum was clean, disposable, and inexpensive.

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The effects of two serotonergic agents--fluoxetine, a serotonin (5-HT) reuptake inhibitor, and buspirone, a 5-HT 1a agonist--on rates of self-injurious and stereotypic behavior were examined in 15 adult male Macaca mulatta. All animals received a placebo for 2 weeks followed by either buspirone or fluoxetine for 12 weeks. Behavior was monitored using a focal sampling technique throughout the study and for 2 weeks post-study. Cerebrospinal fluid (CSF) samples and body weights were obtained pre-study, at the ends of placebo and treatment phases, and post-study. Fluoxetine and buspirone were significantly effective in reducing rates of self-biting during treatment weeks 1 to 8 and self-directed stereotypic behavior during weeks 5 to 12 and post-treatment. No significant effect of either treatment on hair-plucking, stereotypic pacing, saluting, or head tossing was identified. The duration of neutral behavior increased, and rates of scratching and yawning decreased in the buspirone-treated condition. In the fluoxetine-treated condition, rates of yawning, scratching, and self-directed grooming were higher overall compared with those of buspirone-treated animals, and rates of scratching increased significantly (P < 0.05) in weeks 9 to 12; these findings suggest that animals in the fluoxetine-treated condition experienced higher levels of anxiety throughout the study. In both treatment conditions, concentrations of CSF 5-HIAA (5-HT metabolite) were significantly lower (P < 0.05) than placebo concentrations. Fluoxetine and buspirone may be efficacious for treatment of self-injurious and self-directed stereotypic behavior in macaques. Further studies are required to determine the optimal dosages and treatment length.

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We developed procedures to foster orphaned African green monkey infants to females with natural infants of a similar age to the foster infant (< 1 month). Our purpose was to assess the feasibility of fostering additional infants to females with natural infants. The subjects were 4 infants (age 1 to 5 days) that were removed from the natural mother because of neglect or trauma. The recipient females varied in parity (0 to 7 previous infants). Within 24 h of removal from the natural mother, the foster infants were presented to a group of potential recipient females by placing the foster infant directly into the cage of the female that demonstrated positive behavior toward the foster infant (reaching toward the infant and lip-smacking). Analysis of the behavioral data collected when the infants were 3 to 6 months of age indicated that foster mothers spent significantly more time nursing the natural infant alone, but the percentage time spent nursing both infants simultaneously was not significantly different than the time spent nursing either infant individually. No significant differences between weaning weight of the natural and foster infants or single infants were observed at 6 months of age. Overall our success rate at weaning (75%) suggests that fostering additional infants on females with a natural infant may be a viable strategy for raising orphaned African green monkeys and may prevent the development of abnormal behaviors that typically are manifested by nursery-reared infants.

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Social dominance is a fundamental component of both human and nonhuman primate sociality. However, its neurobiological correlates remain incompletely understood. We evaluated the association between dominance status and monoamine metabolite concentrations in cisternal cerebrospinal fluid (CSF) in adult male (n = 25) and female (n = 21) cynomolgus macaques (Macaca fascicularis) housed in unisexual social groups. Concentrations of the metabolites of dopamine (homovanillic acid [HVA]), norepinephrine (3-methoxy-4-hydroxyphenylglycol [MHPG]) and serotonin (5-hydroxyindoleacetic acid [5-HIAA]) were assayed. Dominant monkeys, both males and females, had significantly higher CSF HVA concentrations than did subordinates (p values <.05). Among males, but not females, dominants also had lower CSF 5-HIAA than subordinates (p <.05). The Dominance-HVA association observed here is consistent with recent speculation that social extraversion, a dominance-related personality trait in humans, may also reflect heightened central nervous system dopaminergic activity.

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The current study evaluates the hypothesis, derived from previous investigations, that alterations in dietary fat and cholesterol influence the social behavior of monkeys. Subjects were 62 adult male, cynomolgus macaques (Macaca fascicularis) assigned originally to an investigation of atherosclerosis regression. This study thus involves a secondary analysis of data derived from an investigation conducted for another purpose. Animals were housed for 14 months' in social groups of five individuals each and initially fed a diet very high in saturated fat and cholesterol to induce coronary artery atherosclerosis. Monkeys were then exposed for 28 months to one of three conditions; (1) a moderately high-fat, high-cholesterol diet and an unstable social environment (in which monkeys were switched among groups monthly); (2) a low-fat, low-cholesterol diet and an unstable social environment; and (3) a low-fat, low-cholesterol diet and a stable social environment. A comparison of animals living in unstable groups revealed that those consuming the low-fat diet exhibited more overt aggression (P < 0.001) and overt submission (P < 0.01) than did monkeys eating the high-fat diet. A second comparison involved only those animals living in stable social units. These monkeys, while consuming the low-fat diet, engaged in more aggression and submission (Ps < 0.05), spent less time in passive body contact or within touching distance (Ps < 0.001), and spent more time alone (P < 0.001) than they had initially while consuming a very high-fat diet. The current investigation is the first on this topic to include measures of social behavior in animals both before and after a reduction in dietary fat. The findings that such a reduction is associated with increased agonism and decreased affiliation may help explain the epidemiologic association in human beings between low or reduced plasma cholesterol concentrations and a high incidence of violence-related mortality. More generally, the data are consistent with the hypothesis that there is a negative feedback adaptation providing for appropriate changes in behavior in response to periodic dietary privation. © 1996 Wiley-Liss, Inc.

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Male rhesus monkeys typically disperse from their groups of birth when they are between 3 and 5 years of age. Some males, however, delay dispersal from their natal groups until after they are 5 years old. The current study evaluated central monoaminergic neurotransmitter activity as a potential correlate of such "delayed" dispersal among 54 randomly selected adolescent and adult male rhesus monkeys (Macaca mulatta) captured on Cayo Santiago during an annual trapping season. Specifically, cerebrospinal fluid (CSF) concentrations of 5-hydroxyindoleacetic acid (5-HIAA, a serotonin metabolite), 3-methoxy-4-hydroxyphenylglycol (MHPG, a norepinephrine metabolite), and homovanillic acid (HVA, a dopamine metabolite) were compared in monkeys 60 months of age or more that had either dispersed (n = 33) or were still in their natal groups (n = 5). The monkeys still in their natal groups had higher CSF concentrations of both 5-HIAA and HVA (but not MHPG) than did the animals that had emigrated (Ps < 0.05). Subsequent analysis indicated that only 5-HIAA independently differentiated dispersing monkeys from delayed dispensers. Of monkeys less than 60 months of age (n = 16), only two had dispersed from their natal groups; in this age class, there were no significant differences between dispersing and natal individuals in any CSF monoaminergic metabolite (all Ps = NS). Finally, there was no difference in the CSF 5-HIAA concentrations of the five delayed dispersers and those of younger animals (P = NS), suggesting a failure to experience the frequently reported adolescent decline in serotonergic activity. In contrast, the CSF 5-HIAA concentrations of the dispersing animals were lower than those of the younger animals (P < 0.05), consistent with either an agerelated decline or an effect of dispersal per se. © 1995 Wiley-Liss, Inc.