Seasonal variation in CSF 5-HIAA concentrations in male rhesus macaques.

Seasonal changes in cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations were assessed on multiple occasions in 103 free-ranging male rhesus macaques (Macaca mulatta). At the time of sampling subjects ranged between the ages of 2 and 6 years. CSF samples were collected between the hours of 0900 and 1600 throughout the Fall, Winter, and Spring from 1990 through 1994. Data were analyzed in a general linear mixed model with random intercepts. Results indicated that CSF 5-HIAA concentrations decreased with age. CSF 5-HIAA concentrations were significantly increased in the Fall (October and November), which is the height of the breeding season, with no evidence of differences between Winter and Spring. There was also some evidence that the seasonal variation in CSF 5-HIAA concentrations was blunted in younger, more immature subjects.

CSF 5-HIAA and nighttime activity in free-ranging primates.

Men with low CNS serotonin turnover, as measured by cerebrospinal fluid 5-hydroxyindoleacetic acid (CSF 5-HIAA) concentrations, exhibit aberrant circadian activity patterns characterized by disrupted sleep rhythms and daytime hyperactivity. To assess whether similar patterns are found in nonhuman primates we examined the relationships between CSF 5-HIAA and nighttime activity in free-ranging monkeys. CSF samples were obtained from 16 adult male rhesus macaques living on a 475 acre, heavily forested sea island. Each subject was captured, fitted with a radio-telemetry motion-detector collar, and then released back into its group. A receiver placed near the sleeping trees of the study subjects recorded activity between 2100 hrs and 0600 hrs. Trained observers recorded behavioral data during the day. The animals followed a typical diurnal activity pattern, as they were active 74% of the sampled time during the day and 37% of the sampled time during the night. CSF 5-HIAA concentrations were inversely correlated with total duration of nighttime activity as well as mean duration of all active events. Nighttime activity was inversely correlated with daytime activity. CSF 3-methoxy-hydroxyphenylglycol (MHPG) concentrations were positively correlated with total nighttime activity, and inversely correlated with daytime sleep frequency. We conclude that male rhesus with low CSF 5-HIAA concentrations have higher total nighttime activity, longer mean periods of nighttime activity, and sleep more during the day than do males with high CSF 5-HIAA concentrations. This suggests that low serotonergic neurotransmission is associated with aberrant diurnal activity, as evidenced by a disruption of nighttime sleep patterns and a compensatory higher rate of inactivity during the day.

CSF 5-HIAA and aggression in female macaque monkeys: species and interindividual differences.

RATIONALE: While the relationship among CSF 5-HIAA, impulsivity, and aggression is well characterized in males, its investigation in females is limited, and no studies have assessed its generalizability across primates by making simultaneous comparisons between and within closely-related species. OBJECTIVES: We tested three hypotheses. First, that female rhesus macaques would have lower CSF 5-HIAA concentrations and be more aggressive than would female pigtailed macaques. Second, that females of both macaque species would exhibit an inverse relationship between interindividual differences in CSF 5-HIAA concentrations and rates of severe aggression. Third, that subjects with high CSF 5-HIAA concentrations would be higher in social dominance within their respective groups than would subjects with low CSF 5-HIAA concentrations. METHODS: We obtained CSF samples from 61 individually housed female primates of two closely related species: rhesus macaques (Macaca mulatta) and pigtailed macaques (Macaca nemestrina). We later placed subjects in unisex social groups, and correlated interindividual differences in CSF 5-HIAA with aggression, wounding, and acquisition of social dominance rank. RESULTS: Between-species analyses indicated higher CSF 5-HIAA concentrations in pigtailed macaques, and higher rates of high-intensity aggression, escalated aggression, and wounds requiring medical treatment in rhesus macaques. Within-species analyses indicated that interindividual differences in CSF 5-HIAA concentrations were inversely correlated with escalated aggression and positively correlated with social dominance rank. CONCLUSIONS: These findings show that agonistic and social differences between closely-related species are correlated with CNS serotonin activity, as species that show relatively high rates of severe aggression also tend to have low concentrations of CSF 5-HIAA. We conclude that serotonergic functioning plays an important role in controlling impulses that regulate severe aggression and social dominance relationships in both male and female primates, and that between-species differences in agonistic temperament can be predicted by species typical CNS serotonin functioning.

Trait-like immunological and hematological measures in female rhesus across varied environmental conditions.

In this 2-year longitudinal study, 45 2-year-old female rhesus were observed as they were captured and removed from a free-ranging setting (Phase I), single caged for 1 year (Phase II), and housed in small, stable social groups for an additional year (Phase III). During the study, eight blood samples were taken, and hematological, immunological, and hormonal variables were assayed to determine whether 1) any of the measures would exhibit trait-like, inter-individual longitudinal stability, despite fluctuations in population means induced by Phases I, II, and III; 2) plasma concentrations of cortisol, prolactin, and norepinephrine would be lowest in Phase III, and elevated during the periods of acute and chronic stress associated with Phases I and II; and 3) there would be any evidence of immunosuppression associated with Phases I and II. The results suggest that the majority of hematological/immunological variables were trait-like throughout the study in contrast to plasma cortisol, prolactin, and norepinephrine concentrations. Thus, red blood cells, hemoglobin, hematocrit, platelets, mean corpuscular volume and hemoglobin, as well as white blood cells, the absolute number of CD4+ (T-helper/inducer) cells, the absolute number of CD8+ (T-suppressor/cytotoxic) cells, total T cells (CD2+%), total B cells (CD20+%), and the ratio of CD4+/CD8+ cells were trait-like. The hematological measures were changed dramatically by capture and the subsequent single caging, with most not recovering to presumed baselines until after 12-28 weeks. The immune measures were depressed at capture (excepting B cells), and during 7 months of single caging failed to return to normal levels associated with social housing. We thus conclude that single housing can produce significant, long-term features of immunosuppression. Capture produced significant increases in plasma cortisol, prolactin, and norepinephrine concentrations. Long periods of single caging produced significant increases in plasma prolactin concentrations, indicative of stress-induced anxiety, and may also have been associated with down-regulation of plasma norepinephrine and cortisol concentrations.

Immunization against natural Helicobacter pylori infection in nonhuman primates.

Helicobacter pylori infection is widespread in some breeding groups of a rhesus monkey colony (71% H. pylori positive by 1 year), and the rate of seroconversion is also high. As a result, these groups can be used to test the safety and efficacy of an anti-H. pylori vaccine. Nine-month-old female animals were randomized to receive either 8 mg of recombinant urease (rUre) plus 25 microg of Escherichia coli heat-labile enterotoxin (LT) (n = 26) or placebo plus LT (n = 29), given four times at 1-week intervals followed by a booster 1 month later. Ten months after the start of the immunization, the animals were subjected to endoscopy and biopsy samples were obtained. H. pylori negativity was defined as no H. pylori growth by culture and no H. pylori observed at histology. By this criterion, 2 (7%) of 29 animals receiving placebo and 8 (31%) of 26 immunized animals were H. pylori negative (P < 0.035). In addition, antral gastritis score was significantly less in H. pylori-negative immunized monkeys than in H. pylori-positive animals, whether they were given rUre plus LT or placebo plus LT (P < 0.02 or P < 0.01, respectively). Interestingly, antral gastritis was also significantly less in H. pylori-positive animals given rUre plus LT than in H. pylori-positive animals given placebo plus LT (P < 0.02). However, quantitative cultures did not demonstrate significant differences between the two latter groups. It is concluded that oral administration of rUre vaccine plus LT significantly protects nonhuman primates against H. pylori infection while not causing undesirable side effects.

Evolution of RPS4Y.

Sequence variation within RPS4Y, a ribosomal protein gene located in the nonpseudoautosomal region of the Y chromosome, was used to elucidate the origin of this gene in primates. Complete coding and additional flanking sequences (949 bp) of the RPS4Y locus were determined in four nonhuman primate species. Phylogenetic reconstruction of RPS4 sequence evolution supports the monophyly of mammalian RPS4 and RPS4Y. Molecular evolutionary rate estimation reveals significantly elevated rates of DNA and protein evolution in RPS4Y compared with its X-chromosome homologs. These rates enable us to estimate the timing of the transposition of RPS4X to the Y chromosome (95% confidence interval, 32 MYA-74 MYA), and this estimate was verified by Southern hybridization analysis of prosimian and simian genomic DNA. These data support a transposition event of ancestral primate RPS4X to the Y chromosome prior to the divergence of Prosimii.

CSF 5-HIAA, testosterone, and sociosexual behaviors in free-ranging male rhesus macaques in the mating season.

This study examines sexual behavior, serotonin turnover in the central nervous system, and testosterone in free-ranging non-human primates. Study subjects were 33 young adult male rhesus macaques (Macaca mulatta) living in naturalistic social groups on a 475-acre South Carolina barrier island. Blood and cerebrospinal fluid (CSF) samples were obtained during random trappings, and the subjects were located for observation by radio telemetry. Quantitative behavioral samples totaling 203 observation hours were taken during two mating seasons (September through January) in 1994 and 1995. Control observations (65 h) on 13 subjects were also taken during the non-mating seasons in 1994 and 1995. The results indicate that CSF 5-hydroxyindoleacetic acid (5-HIAA), CSF testosterone, and plasma testosterone concentrations increase significantly during the mating season. During the mating season, there were significant increases in high intensity aggression, low intensity aggression, grooming behavior, and heterosexual mounting. In the mating season, CSF 5-HIAA was significantly correlated with several sociosexual behaviors: consorts per hour, heterosexual mounts per hour, and inseminations per hour. In contrast to previous findings from the non-mating season, CSF 5-HIAA was not correlated with any measures of aggression or sociality, although during consorting, CSF 5-HIAA was positively correlated with grooming. From these findings, we conclude that the lack of correlation between intense and severe aggression and CSF 5-HIAA in the mating season may reflect the use of high intensity aggression in 'normative' male-male competition over access to reproductively active females. We also conclude that CNS serotonin turnover is positively correlated with sexual competence, i.e. males with low CSF 5-HIAA concentrations are less sexually competent than males with higher concentrations.

CSF testosterone and 5-HIAA correlate with different types of aggressive behaviors.

We studied the potential roles of testosterone and serotonin in various forms of aggressive and violent behaviors by measuring each biochemical and behaviour in free-ranging adolescent male nonhuman primates. Our results showed that (1) CSF free testosterone concentrations were positively correlated with overall aggressiveness, but not with measures of impulsivity. (2) CSF 5-HIAA concentrations were negatively correlated with impulsive behavior, and severe, unrestrained aggression, but not with overall rates of aggression. High rates of impulsive behavior were positively correlated with severe, unrestrained aggression, but not overall rates of aggression. (3) Dimensional analyses showed that while subjects with low CSF 5-HIAA exhibited high rates of aggression, high CSF testosterone further augmented rates and intensity of aggression in subjects with low CSF 5-HIAA. We conclude that high CSF free testosterone concentrations are associated with competitive aggression, while low CSF 5-HIAA concentrations are associated with severe aggression which results from impaired impulse control, and perseverance.

Excessive mortality in young free-ranging male nonhuman primates with low cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations.

BACKGROUND: The purpose of this study was to assess the impact of central serotonin turnover rate on survival to adulthood among nonhuman primates living in a large, free-ranging colony. METHODS: The rate of mortality was ascertained over a 4-year period after obtaining blood and cisternal cerebrospinal fluid (CSF) samples from 49 free-ranging, 2-year-old prepubertal male rhesus monkeys. Cerebrospinal fluid was assayed for 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, 3-methoxy-4-hydroxyphenylgycol, and homovanillic acid. Blood plasma was assayed for adrenocorticotropic hormone, cortisol, and testosterone. Following the sampling of body fluids, records of scars and wounds and aggressive encounters were used to rank the subjects from low to high in aggressiveness. Direct observations of aggressive behavior were collected from 27 of the subjects over a 3-month period. RESULTS: Four years later, 6 of the 49 subjects were known to be dead and an additional 5 had been missing for more than 2 years and were presumed dead. The CSF 5-HIAA concentrations were predictive of which subjects died, with 46% of the subjects with low CSF 5-HIAA concentrations dead or presumed dead. None of the subjects from the highest CSF 5-HIAA concentration quartile were dead or missing. Indeed, 91% of the dead subjects came from the 2 lowest quartiles of CSF 5-HIAA concentrations. Direct observations of aggressive behavior showed that dead or missing subjects had initiated escalated aggression, a measure of unrestrained aggression that has a high probability of trauma or injury, at a higher rate than subjects that were known to be alive. The cause of death could be ascertained for 6 of the 11 missing subjects. The 4 subjects that were known to die as a consequence of aggressive encounters came from the lowest quartile of CSF 5-HIAA concentrations and had been rated as more aggressive during their initial capture. Subjects captured more than once possessed lower CSF 5-HIAA concentrations, were rated as more aggressive, and were more likely to suffer early death than those captured only once. CONCLUSION: These findings suggest that low CSF 5-HIAA concentrations quantified early in life is a powerful biological predictor of future excessive aggression, risk taking, and premature death among nonhuman primate males.

Correlation of CSF 5-HIAA concentration with sociality and the timing of emigration in free-ranging primates.

OBJECTIVE: The purpose of this study was to examine the relationship between behavior and serotonin in nonhuman primates. METHOD: During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Blood samples (N = 23) and CSF samples (N = 22) were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. RESULTS: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentration was positively correlated with three measures of sociality: 1) total time spent grooming others, 2) total time spent in close proximity to other group members, and 3) mean number of neighbors within a 5-m radius. In addition, CSF 5-HIAA concentration was positively correlated with age at emigration from the natal group (in months). CONCLUSIONS: In adolescent male rhesus macaques living in naturalistic settings, CSF 5-HIAA concentration is positively correlated with affiliative sociality. Rhesus males with low CSF 5-HIAA concentrations exhibit less social competence and emigrate from their social groups at a younger age than do males with higher concentrations of CSF 5-HIAA.

Seroepizootiology of Helicobacter pylori gastric infection in nonhuman primates housed in social environments.

We determined the seroepizootiology of Helicobacter pylori infection in rhesus monkeys. Plasma was obtained from 196 animals (age range, 1 to 22 years) that were housed in social environments, either in indoor gang cages, in outdoor corrals, or in free-ranging forested conditions. Plasma immunoglobulin G levels were determined with a specific enzyme-linked immunosorbent assay, and the cutoff immunoglobulin G value for H. pylori seropositivity was determined from a study of 25 monkeys whose infection status was assessed by light microscopy and culture. One-year-old animals of both genders in all housing conditions had the lowest rate of positivity (60% in monkeys 1 year old versus 81% in monkeys 2 to 10 years old, P = 0.026). In addition, females tended to have higher rates of positivity than males. Seroconversion during a 1-year observation period occurred in 7 (28%) of 25 seronegative animals. Seroreversion occurred in 3 (4%) of the 78 positive animals; all 3 of these animals had received antimicrobial agents during the year. These observations demonstrate that the epizootiology of H. pylori infection in rhesus monkeys may serve as a model for human infection.

Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates.

OBJECTIVE: The purpose of this study was to examine the relationship between behavior and serotonin by using a nonhuman primate model of aggression and impulse control. METHOD: During a routine capture and medical examination, 26 adolescent male rhesus macaques (Macaca mulatta) were selected as subjects from a free-ranging population of 4,500 rhesus monkeys inhabiting a 475-acre sea island. Physiological data were obtained from 22-23 of the subjects. Blood and CSF samples were obtained, and each subject was fitted with a radio transmitter collar for rapid location. The subjects were released into their social groups, and quantitative behavioral observations were made over a 3-month period. RESULTS: CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were inversely correlated with "escalated" aggression, i.e., a measure of more intense or severe aggression as defined by the ratio of chases and physical assaults to all aggressive acts. CSF 5-HIAA concentrations were significantly lower in those subjects who showed evidence of physical wounding than in subjects with no wounds. Low CSF 5-HIAA concentrations were also correlated with greater risk-taking as determined by an analysis of leaping behaviors in the forest canopy. The ratio of long leaps (leaps that traversed the longest distances at dangerous heights) to all leaps was negatively correlated with CSF 5-HIAA concentrations. CONCLUSIONS: Adolescent male rhesus macaques with low CSF 5-HIAA concentrations are at risk for 1) exhibiting more violent forms of aggressive behavior and 2) loss of impulse control as evidenced by greater risk taking during movement through the forest canopy.

Cerebrospinal fluid monoamine and adrenal correlates of aggression in free-ranging rhesus monkeys.

Clinical and preclinical studies involving several different mammalian species and research paradigms suggest a negative correlation between aggression and central serotonin activity. To test the generalizability of laboratory findings in rhesus monkeys that show a negative correlation between cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations and aggression, we obtained cisternal cerebrospinal fluid and blood plasma samples from monkeys living in naturalistic conditions. During a semiannual trapping, 28 juvenile and adolescent male rhesus monkeys were chosen from a population of 4200 provisioned, free-ranging rhesus monkeys living on Morgan Island, a sea island located off the coast of South Carolina. Based on direct observations of participation or avoidance of aggressive behavior and examinations of apparent fight wounds, 18 monkeys were selected for cerebrospinal fluid taps and blood samples. The remaining 10 monkeys were selected at random. Descriptions of aggressive behavior and the number of old scars and recent wounds were carefully transcribed, and a photograph showing wounds and scars was obtained for each animal. Using the transcriptions and photographs, researchers experienced in rhesus monkey behavior, but blind to the subjects' monoamine and hormone concentrations, were asked to rank the monkeys from the most to the least aggressive. The results showed a significant negative correlation between high rankings for aggression and cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations. There was evidence that aggression was associated with stress, in that cerebrospinal fluid, norepinephrine, and plasma corticotropin and cortisol concentrations were positively correlated with high rankings of aggression.

Development of the Morgan Island rhesus monkey colony.

During the summer of 1979, the rhesus monkey breeding colony of the La Parguera facility of the Caribbean Primate Research Center was shipped to Morgan Island, South Carolina. During six shipments in 1979, and three more in 1980, over 1400 animals were translocated. Mortality from shipping, primarily in infants, was approximately 0.65%. Although the monkeys were not shipped in intact social groups, they restablished their groups shortly after subunits were released onto Morgan Island (MI). Since 1979 the colony has grown almost four-fold and now numbers almost 4000 animals. There has always been a strong female bias in the colony and today females comprise 75% of the total population. That portion of the colony comprising the aged animals, especially females, has grown steadily and today is 13% of the total. Except for the first year, when the colony was translocated during its mating season, reproduction at MI has been good, with a pooled average pregnancy rate of almost 80% and live birth rate of 71%. Juvenile females have also reproduced well, averaging 76% pregnancy and 70% live birth rates. This experience demonstrates that with proper planning and execution, a large, free-ranging colony can be moved long distances with minimal stress, trauma, mortality or disruption of social structure and reproduction.

Intergroup interactions in wild Barbary macaques (Macaca sylvanus), Ghomaran Rif mountains, Morocco.

Data are presented on intergroup interactions between six groups of Macaca sylvanus in the Ghomaran region of the Moroccan Rif mountains. Intergroup encounters (0.026/observation hour) were defined as two groups being near each other (< 150 m). Encounters were further classified into: 1) neutral (indeterminate) encounters, in which very little intergroup interaction took place, with the exception of male monitoring (N = 7); 2) approach-retreat encounters with intergroup displacement, in which, without any overt agonism, members of one group slowly approached another and caused it to retreat (N = 3); and 3) agonistic encounters with intergroup displacement (N = 3). These results are compared to the only other study of intergroup interactions in wild Barbary macaques, and it is concluded that 1) observations of intergroup unification and/or coordination of movement in Barbary macaques ("herding") probably resulted from observer error, or if these phenomena do occur, they are rare throughout the range of this species; 2) approximately half of all intergroup encounters in both studies resulted in intergroup displacement and/or intergroup agonism, evidence of intergroup competition; and 3) current data on intergroup interactions in Barbary macaques conform to the predictions of Wrangham's model of mutually competitive female-bonded, multimale groups.