Early experience and low 5-HT markers in alcohol abuse

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DESCRIPTION (provided by applicant): Adolescents of middle school and high school age are at high risk for alcohol consumption. Nonhuman primates living in social groups provide an excellent model for the study of social influences on biobehavioral development in general and alcohol abuse problem more specifically. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) is interested in encouraging investigators with expertise in primate developmental biology and behavior to seek collaborations with established alcohol researchers to elucidate the neurobiological mechanisms of adolescent alcohol abuse and alcoholism. Herein we submit a revision of a model of biobehavioral development that focuses on the origins of individual differences in voluntary alcohol consumption in young socially housed bonnet macaque monkeys. Differences in early maternal care are suggested as one basis for differences in relative risk for consuming higher quantities of ethanol. Biomarkers of the activity of the serotonergic system (CSF 5HIAA and the prolactin response to fenfluramine) will be evaluated. Subjects will be selected on the basis of a polymorphism in the promoter region of the serotonin transporter protein gene that modulates serotonergic activity. Maternal care will be determined through observation of mother infant interactions during early development in social group reared macaque monkeys. We hypothesize that monkeys experiencing poor quality maternal care during development will demonstrate increased risk for the expression of aggressive and impulsive behavior patterns as adolescents. We hypothesize that these behavior patterns will be present in monkeys that voluntarily consume greater quantities of ethanol. Low serotonin will have an additive effect with low quality maternal care on levels of aggression, impulsivity, and alcohol consumption. We predict that adolescent monkeys evidencing higher aggressive and impulsive behavior patterns and low serotonin will show 1) increased rates of ethanol consumption under social conditions, 2) a greater increase in ethanol intake in response to a stressor, 3) higher probability that ethanol consumption will be associated with increased aggression when housed socially, and 4) attenuated soporific effects. Finally, involvement of the HPA axis in these relationships will be investigated as an exploratory goal.