Biomedical subjects

J Dee Higley

Publications and source records attributed to J Dee Higley.

At least 19 recordsLinked to original sources

PubMed2006

Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats.

RATIONALE: Application of the Fischer-Lewis genetic model of drug abuse to the study of alcohol's motivational properties has been limited. OBJECTIVES: To assess the aversive and rewarding effects of ethanol in Fischer and Lewis rats. MATERIALS AND METHODS: Fischer and Lewis rats underwent a four-trial combined conditioned taste aversion/conditioned place preference procedure (CTA/CPP; 0, 1, 1.25, or 1.5 g/kg IP ethanol). Others received 0, 1, or 1.5 g/kg followed by tail blood sampling at 15-, 60- and 180-min post-injection. In additional groups, hypothermia to 0, 1.5, and 3 g/kg was assessed before and 30- and 60-min post-injection. RESULTS: All alcohol-treated groups except low-dose Lewis acquired CTA after one trial. Fischer rats developed stronger CTAs than Lewis at 1.25 and 1.5 g/kg. Ethanol-induced reward in taste or place conditioning was not evident in either strain. Lewis animals showed overall higher peak blood alcohol concentrations, but hypothermia did not vary by strain. CONCLUSION: Compared to Fischer, Lewis rats are less sensitive to alcohol's aversive effects as assessed in the CTA paradigm. The behavioral differences observed are not due to hypothermia, but pharmacokinetic differences may contribute. These data underscore the importance of genetic factors and the aversive effects of initial drug exposures in modeling vulnerability to abuse. In addition to its application with other drugs, the Fischer-Lewis model may be useful for investigating the biobehavioral bases of alcohol abuse.

Alcohol Drinking↗

PubMed2006

Influence of parenting style on the offspring's behaviour and CSF monoamine metabolite levels in crossfostered and noncrossfostered female rhesus macaques.

We investigated the association between variation in parenting style and the offspring's behaviour and CSF monoamine metabolite (5-HIAA, HVA, and MHPG) levels in rhesus monkeys. Study subjects were 25 two-year-old females reared by their biological mothers and 15 same-aged females that were crossfostered at birth and reared by unrelated mothers. Subjects that were rejected more by their mothers in the first 6 months of life engaged in more solitary play and had lower CSF concentrations of 5-HIAA than subjects that were rejected less. The relation between these variables was generally similar in crossfostered and noncrossfostered females. CSF levels of 5-HIAA were negatively correlated with rates of scratching, a behavioural indicator of anxiety. These results suggest that that early exposure to high rates of maternal rejection can result in higher anxiety later in life, and that this effect may be mediated by serotonergic mechanisms. Variation in maternal protectiveness did not affect offspring behaviour and neither protectiveness nor rejection affected CSF levels of HVA and MHPG. CSF levels of MHPG, however, were negatively correlated with solitary play behaviour and avoidance of other individuals, suggesting that individuals with lower CSF MHPG were more fearful and socially phobic than those with higher CSF MHPG. Taken together, these findings suggest that individual differences in anxiety and fearfulness in young rhesus monkeys are accounted for, at least in part, by variation in CSF levels of monoamine metabolites, and that the development of brain monoamine systems, particularly serotonin, can be affected by early exposure to variable maternal behaviour.

Analysis of Variance↗

PubMed2006

Effects of early life stress on [11C]DASB positron emission tomography imaging of serotonin transporters in adolescent peer- and mother-reared rhesus monkeys.

Peer-reared (PR) rhesus monkeys with early maternal separation later exhibit aggressiveness, impaired impulse control, alcohol abuse, and low CSF 5-hydroxyindoleacetic acid. This study compared regional brain serotonin transporter (SERT) binding between nine PR and seven mother-reared rhesus monkeys with [11C]DASB positron emission tomography (PET) imaging. Parametric images of binding potential (BP) (which is proportional to Bmax/KD, in which Bmax is transporter density and KD is dissociation constant) and relative blood flow (R1) were generated by the two-parameter multilinear reference tissue model. R1 images were used for coregistration and normalization of PET parametric data to the magnetic resonance imaging template space. Group BP differences were analyzed voxelwise by Student's t test in SPM2. Region of interest-based parameter values were also calculated to obtain the magnitude of regional BP differences between the two groups. For the PR group, SERT BP was decreased by 10-23% across a range of brain areas consisting of the raphe, thalamus, hypothalamus, caudate and putamen, globus pallidum, anterior cingulate gyrus, and medial temporal regions, including amygdala and hippocampus (cluster-level corrected p = 0.002). For the latter three regions, BP was decreased in the right hemisphere. These results agree with the hypothesis that early maternal deprivation affects the development of the serotonergic system and suggest that decreased serotonergic innervations in the critical brain regions may explain some of the behavioral and biochemical abnormalities in PR monkeys.

Aging↗

PubMed2006

Left versus right nipple preference in free-ranging infant rhesus macaques (Macaca mulatta).

The examination of nonhuman primate (NHP) lateralized behaviors may provide insight into the evolution of hemispheric specialization. This study examined nipple preference in 64 infant macaques in order to consider the ontogeny of lateralized behavior. We used a focal animal sampling method to record nipple contact during 15, 30-min observation sessions collected across each infant's first year of life. Using a lateralized behavior index (LBI) we calculated individual and population preferences (LBI=(R-L)/(R+L); "R"=mean right nipple contact, "L"=mean left nipple contact). Strength of preference was calculated as the absolute value of this score. Infants exhibited no population preference for a particular nipple, but showed a significant strength of preference that developed after 48 hr. Interestingly, successive siblings preferred the nipple not used by the previous infant. These findings suggest that nipple preference is guided by external stimuli, and that nipple preference during infancy may not be a behavioral representation of hemispheric specialization.

Age Factors↗

PubMed2006

Early maternal rejection affects the development of monoaminergic systems and adult abusive parenting in rhesus macaques (Macaca mulatta).

This study investigated the effects of early exposure to variable parenting style and infant abuse on cerebrospinal fluid (CSF) concentrations of monoamine metabolites and examined the role of monoaminergic function in the intergenerational transmission of infant abuse in rhesus monkeys (Macaca mulatta). Forty-three infants reared by their biological mothers and 15 infants that were cross-fostered at birth and reared by unrelated mothers were followed longitudinally through their first 3 years of life or longer. Approximately half of the infants were reared by abusive mothers and half by nonabusive controls. Abused infants did not differ from controls in CSF concentrations of 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), or 3-methoxy-4-hydroxyphenylgycol (MHPG). Abused infants, however, were exposed to higher rates of maternal rejection, and highly rejected infants had lower CSF 5-HIAA and HVA than low-rejection infants. The abused females who became abusive mothers in adulthood had lower CSF 5-HIAA than the abused females who did not. A similar trend was also observed among the cross-fostered females, suggesting that low serotonergic function resulting from early exposure to high rates of maternal rejection plays a role in the intergenerational transmission of infant abuse.

Age Factors↗

PubMed2006

Genetic and other contributions to alcohol intake in rhesus macaques (Macaca mulatta).

BACKGROUND: The etiology of alcoholism and alcohol abuse, like many other complex diseases, is heterogeneous and multifactorial. Numerous studies demonstrate a genetic contribution to variation in the expression of alcohol-related disorders in humans. Over the past decade, nonhuman primates have emerged as a valuable model for some aspects of human alcohol abuse because of their phylogenetic proximity to humans. Long-term, longitudinal studies of rhesus macaques (Macaca mulatta) have provided much insight into environmental influences, especially early life experiences, on alcohol consumption and behavior patterns that characterize alcohol intake later in life. It is not known, however, whether there is a genetic component as well to the variation seen in alcohol consumption in rhesus macaques. A significant genetic component to variation in alcohol consumption in rhesus macaques would show for the first time that like humans, for nonhuman primates additive genetic influences are important. Moreover, their use as a model for alcohol-related disorders in humans would have even greater relevance and utility for designing experiments incorporating the expanding molecular genetics field, and allow researchers to investigate the interaction among the known environmental influences and various genotypes. METHODS: In this study, we investigate factors contributing to variation in alcohol consumption of 156 rhesus macaques collected over 10 years when subjects were adolescent in age, belonging to a single extended pedigree, with each cohort receiving identical early rearing backgrounds and subsequent treatments. To measure alcohol consumption each animal was provided unfettered simultaneous access both to an aspartame-sweetened 8.4% (v/v) alcohol-water solution, the aspartame-sweetened vehicle, and to water for 1 hour each day during the early afternoon between 13:00 and 15:00 in their home cages for a period of 5 to 7 weeks. We use multiple regression to identify factors that significantly affect alcohol consumption among these animals and a maximum likelihood program (ASReml) that, controlling for the significant factors, estimates the genetic contribution to the variance in alcohol consumption. RESULTS: Multiple regression analysis identified test cohort and rearing environment as contributing to 57 and 2%, respectively, of the total variance in alcohol consumption. Of the remaining 41% of the variance about half (19.8%) was attributable to additive genetic effects using a maximum likelihood program. CONCLUSION: This study demonstrates that, as in humans, there are additive genetic factors that contribute to variation in alcohol consumption in rhesus macaques, with other nongenetic factors accounting for substantial portions of the variance in alcohol consumption, Our findings show the presence of an additive genetic component and suggest the potential utility of the nonhuman primate as a molecular genetics tool for understanding alcohol abuse and alcoholism.

Alcohol Drinking↗

PubMed2005

Increased viral replication in simian immunodeficiency virus/simian-HIV-infected macaques with self-administering model of chronic alcohol consumption.

Alcohol abuse constitutes a major cohort among HIV-infected individuals. The precise effect of alcohol addiction on HIV pathogenesis remains inconclusive, however. This study was designed to determine the effect of alcohol dependence on virus replication and CD4 profiles in simian immunodeficiency virus/simian-HIV-infected rhesus macaques. A group of 3 male Indian rhesus macaques was adapted to a self-drinking model of alcohol consumption, whereas another group of 3 macaques was provided a Nutrasweet solution. After 7 weeks of alcohol consumption, the alcohol-dependent animals along with controls were intravenously inoculated with a mixture of SHIV(KU), SHIV(89.6)P, and SIV/17E-Fr. These animals were followed for a period of 24 weeks for complete blood cell counts, CD4 cell profiles, and viral loads in the blood and cerebral compartments. The alcohol and control groups showed comparable peak viral loads in the blood. The plasma viral load in the alcohol group was 31- to 85-fold higher than that in the control group at weeks 18 through 24 after infection, however. The pattern of cerebrospinal fluid viral replication was also comparable during the acute phase; however, the virus continued to replicate in the brain of alcohol-dependent animals, whereas it became undetectable in the controls. The extent of CD4 cell loss in the alcohol group was significantly higher than that in the control animals at week 1 after infection.

Alcoholism↗

PubMed2005

Monoamine oxidase A gene promoter variation and rearing experience influences aggressive behavior in rhesus monkeys.

BACKGROUND: Allelic variation of the monoamine oxidase A (MAOA) gene has been implicated in conduct disorder and antisocial, aggressive behavior in humans when associated with early adverse experiences. We tested the hypothesis that a repeat polymorphism in the rhesus macaque MAOA gene promoter region influences aggressive behavior in male subjects. METHODS: Forty-five unrelated male monkeys raised with or without their mothers were tested for competitive and social group aggression. Functional activity of the MAOA gene promoter polymorphism was determined and genotypes scored for assessing genetic and environmental influences on aggression. RESULTS: Transcription of the MAOA gene in rhesus monkeys is modulated by an orthologous polymorphism (rhMAOA-LPR) in its upstream regulatory region. High- and low-activity alleles of the rhMAOA-LPR show a genotype x environment interaction effect on aggressive behavior, such that mother-reared male monkeys with the low-activity-associated allele had higher aggression scores. CONCLUSIONS: These results suggest that the behavioral expression of allelic variation in MAOA activity is sensitive to social experiences early in development and that its functional outcome might depend on social context.

Aggression↗

PubMed2005

Social withdrawal behaviors in nonhuman primates and changes in neuroendocrine and monoamine concentrations during a separation paradigm.

This study investigated relationships between withdrawal behaviors in rhesus macaques and changes in monoamine metabolite and endocrine concentrations during repeated psychosocial stress. Rhesus monkeys (N = 71) experienced maternal separation in which four separations took place during four consecutive weeks. Behavioral observations were made, as well as plasma concentrations of cortisol and cerebrospinal fluid concentrations of the serotonin, dopamine, and norepinephrine metabolites were obtained. Animals were assigned to high, moderate, and low withdrawal groups, defined using baseline durations of withdrawal behaviors. Highly withdrawn animals showed less reduction than nonwithdrawn animals in serotonin metabolite concentrations over repeated separations. Highly withdrawn macaques also failed to significantly reduce cortisol concentrations across separation weeks. More adaptation in central serotonin functioning and cortisol concentrations was seen in nonwithdrawn primates than in highly withdrawn primates; these findings have implications for increased risk of developing anxiety disorders in highly inhibited children.

Animals↗

PubMed2005

The effects of fluoxetine and buspirone on self-injurious and stereotypic behavior in adult male rhesus macaques.

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.

Animals↗

PubMed2004

Neurobiological characteristics of rhesus macaque abusive mothers and their relation to social and maternal behavior.

Previous studies have reported hyperactivation of catecholaminergic systems and elevated concentrations of corticotropin-releasing-hormone (CRH) in the cerebrospinal fluid (CSF) of child maltreatment victims or combat veterans with post-traumatic stress disorder (PTSD). This study investigated the CSF concentrations of CRH and monoamine metabolites in rhesus macaque mothers that physically abused their infants and had themselves been abused as infants. Ten abusive mothers and 10 controls served as study subjects. All animals were sampled for CSF during pregnancy and the postpartum period. Focal observations of social and maternal behavior were also made. Abusive mothers had significantly higher CSF concentrations of CRH and 5-HIAA than controls. Across both subjects and controls, higher CRH, 5-HIAA and MHPG concentrations were associated with anti-social behavior patterns including a high frequency of maternal aggression, infant rejection, and a low frequency of contacts received from other individuals. These findings are consistent with those of previous primate and human studies and suggest that the neurobiological alterations associated with infant abuse may play an important role in the occurrence of maladaptive behavior in adulthood, including the perpetuation of infant abuse across generations.

Aggression↗

PubMed2004

Time course of the effects of the serotonin-selective reuptake inhibitor sertraline on central and peripheral serotonin neurochemistry in the rhesus monkey.

RATIONALE: Fundamental questions remain regarding the actions of the selective serotonin reuptake inhibitors (SSRIs). OBJECTIVES: To examine the time course of central and peripheral neurochemical effects of sertraline (SER) in non-human primates. METHODS: SER (20 mg/kg, p.o.) or placebo were administered daily for 4 weeks to two groups of six young adult male rhesus monkeys. Both groups received placebo during a 3-week baseline lead-in period and for 6 weeks after discontinuation. Blood and cisternal cerebrospinal fluid (cCSF) samples were obtained on days -21, -14, -7, 0, +3, +7, +14, +21, +28, +35 and +70. RESULTS: In animals receiving SER, mean (+/-SD) levels of cCSF serotonin (5-HT) increased from 38.6+/-9.0 pg/ml at baseline to 128+/-46.4 pg/ml during treatment (paired t=4.17, P=0.014). Concentrations of cCSF 5-HT were 290% of baseline on day 0 (+3 h), ranged from 260% to 436% of baseline during treatment, and returned to baseline 7 days after discontinuation. Levels of cCSF 5-hydroxyindoleacetic acid declined to 51+/-2.0% of baseline by day +3 and remained at similarly reduced levels during treatment. Plasma drug levels and decrements in platelet 5-HT were similar to those seen in patients. CONCLUSIONS: SER rapidly and substantially increases cCSF levels of 5-HT in primates, the extent of elevation is relatively constant during prolonged administration, and values return to baseline shortly after discontinuation. The results suggest that response latency for SSRIs in depression is not due to gradually increasing brain extracellular fluid 5-HT levels and tend not to support theories that posit SSRI response latency as being due to autoreceptor desensitization, transporter downregulation, or drug accumulation.

Animals↗

PubMed2004

Sexual dichotomy of an interaction between early adversity and the serotonin transporter gene promoter variant in rhesus macaques.

A polymorphism in the human serotonin transporter gene promoter (5-HTTLPR) is associated with anxiety and increased risk for developing depression in the face of adversity. Here, we report that among infant rhesus macaques, an orthologous polymorphism (rh5-HTTLPR) interacts with adversity in the form of peer rearing to influence adrenocorticotropic hormone (ACTH) response to stress and, further, that this interaction is sexually dichotomous. ACTH responses to separation are higher in l/s than in l/l males. In females, however, it is only among those with a history of adversity that the s allele is associated with increased ACTH responses to stress. Of interest, peer-reared animals, in particular females carrying the s allele, also exhibit lower cortisol responses to stress, a pattern that has been recognized in association with certain stress-related neuropsychiatric disorders. By extension, our findings suggest the intriguing possibility that human females carrying the 5-HTTLPR s allele could be more vulnerable to the effects of early adversity. This interactive effect may underlie the increased incidence of certain stress-related disorders in women.

Adrenocorticotropic Hormone↗

PubMed2004

Rearing condition and rh5-HTTLPR interact to influence limbic-hypothalamic-pituitary-adrenal axis response to stress in infant macaques.

BACKGROUND: In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety. Serotonin transporter gene disruption in rodents produces anxious animals with exaggerated limbic-hypothalamic-pituitary-adrenal (LHPA) responses to stress. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence endocrine responses to stress in infant rhesus macaques. METHODS: Animals were reared with their mothers (MR, n = 141) or in peer-only groups (PR, n = 67). At 6 months of age, adrenocorticotropic hormone (ACTH) and cortisol levels were determined at baseline and during separation stress. Serotonin transporter genotype (l/l and l/s) was determined with polymerase chain reaction followed by gel electrophoresis. RESULTS: Cortisol levels increased during separation, and there was a main effect of rearing condition, with decreased cortisol levels among PR macaques. Animals with l/s rh5-HTTLPR genotypes had higher ACTH levels than did l/l animals. Adrenocorticotropic hormone levels increased during separation, and there was a separation x rearing x rh5-HTTLPR interaction, such that PR-l/s animals had higher ACTH levels during separation than did other animals studied. CONCLUSIONS: These data demonstrate that serotonin transporter gene variation affects LHPA axis activity and that the influence of rh5-HTTLPR on hormonal responses during stress is modulated by early experience.

Animals↗

PubMed2004

Characterization of the rhesus monkey ghrelin gene and factors influencing ghrelin gene expression and fasting plasma levels.

Ghrelin stimulates release of GH from the pituitary, stimulates appetite, and may influence metabolic processes in other tissues expressing the GH secretagogue receptor. Ghrelin can thus influence behaviors and endocrine pathways contributing to weight gain. In this study we characterized the ghrelin gene from the rhesus monkey and analyzed the association of plasma ghrelin levels with metabolic and endocrine markers. Rhesus ghrelin is 97, 91, and 96% homologous to the human cDNA, gene, and peptide, respectively. Ghrelin expression was highest in the stomach with lower levels found in muscle and duodenum. In these tissues, ghrelin expression in calorie-restricted and obese animals was about 40-99% lower than in lean animals. In addition, ghrelin expression in muscle was fairly high and may allow this tissue to contribute significantly to plasma levels. Fasting plasma ghrelin concentrations were also inversely correlated with body mass index and exhibited a nonlinear association with age with increased levels in younger and older monkeys and lower levels in middle-aged monkeys. Although a significant inverse correlation between fasting plasma ghrelin and fasting insulin levels were found, iv glucose and insulin administration did not significantly alter ghrelin levels. These studies demonstrate that ghrelin levels are influenced by age-related factors and adiposity in the rhesus monkey. These similarities between the rhesus monkey and human ghrelin genes and plasma ghrelin responses suggest a unique opportunity to study the mechanisms regulating ghrelin secretion and gene expression in different tissues in normal and disease states using this model system.

Aging↗

PubMed2004

Interaction between serotonin transporter gene variation and rearing condition in alcohol preference and consumption in female primates.

BACKGROUND: Serotonin neurotransmission and limbic-hypothalamic-pituitary-adrenal (LHPA) axis hormones are thought to be involved in the reinforcement of alcohol intake and contribute to the risk for alcoholism. In humans and macaques, a promoter polymorphism that decreases transcription of the serotonin transporter gene is associated with anxiety and altered LHPA-axis responses to stress, and in female macaques, exposure to early-life stress alters LHPA-axis activation in response to alcohol. We wanted to determine whether serotonin transporter gene promoter variation (rh-5HTTLPR) and rearing condition would interact to influence alcohol preference in female rhesus macaques. Because of the involvement of stress and LHPA-axis activity in symptoms of withdrawal and relapse, we also wanted to determine whether serotonin transporter gene variation and rearing condition would influence changes in the patterns of alcohol consumption across a 6-week alcohol consumption paradigm. METHODS: Female macaques were reared with their mothers in social groups (n = 18) or in peer-only groups (n = 14). As young adults, they were given access to an aspartame-sweetened 8.4% alcohol solution and vehicle for 1 hour per day, and volumes of consumption of alcoholic and nonalcoholic solutions were recorded. Serotonin transporter genotype (l/l and l/s) was determined using polymerase chain reaction followed by gel electrophoresis. RESULTS: We found interactions between rearing condition and serotonin transporter genotype, such that l/s peer-reared females demonstrated higher levels of ethanol preference. We also found an effect of rearing condition on the percentage change in alcohol consumed during the 6 weeks as well as a phase by rearing interaction, such that peer-reared animals progressively increased their levels of consumption across the course of the study. This was especially evident for peer-reared females with the l/s rh5-HTTLPR genotype. CONCLUSION: These data suggest a potential interaction between serotonin transporter gene variation and early experience in vulnerability to alcoholism.

Alcohol Drinking↗

PubMed2004

Physiological predictors of reproductive outcome and mother-infant behaviors in captive rhesus macaque females (Macaca mulatta).

Previous research has shown that offspring of females with low cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) concentrations are less likely to survive the first year of life than are offspring of females with high CSF 5-HIAA concentrations. In addition, studies of free-ranging rhesus macaque males have suggested that individuals with low CSF 5-HIAA concentrations suffer reduced reproductive success relative to their high serotonin counterparts. We examined CSF concentrations of the monoamine metabolites 5-HIAA and homovanillic acid (HVA), and plasma cortisol concentrations as predictors of first-time adult reproductive potential, maternal behavior, and overall social interactions in two groups of captive female rhesus macaques and their first offspring. Repeated CSF and blood samples were obtained from adult females in two social groups, and focal observations were performed for both new mothers and infants during the first month following parturition. We found that the reproductively aged nulliparous females who failed to give birth to their first offspring showed significantly lower CSF 5-HIAA concentrations than those females who gave birth. Among those females that gave birth to offspring, females with low CSF 5-HIAA concentrations and females with high plasma cortisol concentrations were overly protective and restrictive with their infants. CSF HVA concentration was not associated with reproductive output, social behavior, aggression, or mother-infant interactions in this sample of rhesus macaque females. We conclude that low CNS serotonin activity and high stress, measured by high plasma cortisol, are correlated with reduced reproductive success and patterns of high maternal restrictiveness in young adult female rhesus macaques.

Aggression↗

PubMed2004

The use of adolescent nonhuman primates to model human alcohol intake: neurobiological, genetic, and psychological variables.

Traits characteristic of type I and type II alcoholism are thought to relate to dysregulated central nervous system serotonin functioning. In this review, we discuss variables associated with high adolescent alcohol consumption and other risk-taking behaviors in a nonhuman primate model. Adolescent primates with low CSF concentrations of the serotonin metabolite 5-HIAA are more impulsive and exhibit increased levels of alcohol consumption. Both genetic and environmental factors contribute to alcohol-seeking behavior in adolescent macaques. Sequence variation within serotonin system genes, for example, a repeat polymorphism in the transcriptional control region of the monoamine oxidase gene (MAOA-LPR), increases the propensity for adolescent males to consume alcohol. Environmental factors, such as early life stress in the form of peer-rearing or early age of exposure to alcohol, are also associated with increased alcohol consumption. Peer-reared females, especially those exposed to alcohol during early adolescence, exhibit increased rates of alcohol consumption compared to those exposed to alcohol later in development. When genetic variables are also considered, there is an interaction between the low activity serotonin transporter gene promoter s allele (rh5-HTTLPR) and rearing condition on alcohol preference in females but not males, suggesting that the interactions between genes and the environment may be sexually dichotomous. By learning more about the interactions between genes, early experience, and alcohol intake in the adolescent nonhuman primate, we may be able to identify factors that contribute to the susceptibility, pathogenesis, and progression of impulse control disorders, such as alcoholism.

Adolescent↗