Adolescent alcohol abuse has now reached epidemic proportions, carrying with it a toll of lost opportunity, suffering and death. There is growing realization that, because of its very nature, adolescence is a period of increased risk for abusive behaviors of all kinds, and at the same time, a concern that the adolescent brain may be particularly vulnerable to the toxic insults of ethanol and other drugs of abuse. It is not clear what the precise nature of these neurobiological risks is, and for ethical reasons, it is not possible to address this question directly in man. We propose here a pilot study of the feasibility of addressing this question experimentally, capitalizing upon an animal model of spontaneous alcohol abuse. C. aethiops, a non-endangered African primate, is highly homologous with man, lives in social groups, has a distinct adolescent period in its ontogeny, and contains individuals who differ from one another with respect to alcohol consumption and to behavioral traits (sociability, excitability, etc.) We have recently developed a relatively simple test which probes the neurochemical correlates of acute response to an ethanol challenge in this species, and have obtained preliminary data suggesting that this response is correlated with later voluntary consumption of beverage alcohol. In the present project, we will document the developmental stability of this measure in a cross-section of the juvenile population, and explore the further neurochemical and behavioral correlates of this response. Particular attention will be given to markers of dopaminergic neurotransmission (dopamine transporter, D1 and D3 receptors), which have previously been shown to discriminate alcohol-preferring from alcohol-avoiding adult vervet monkeys. The extent to which sensitivity to ethanol is correlated with other neurotransmitter markers (serotonin, GABA, glutamate) known to regulate dopamine neurotransmission or dopamine availability will also be explored. In an unbiased microarray study, we will also seek to identify novel candidate genes which are significantly elevated or reduced in vervets with high and low sensitivity to the neurochemical effects of beverage alcohol. These studies should provide information directly relevant to the identification of susceptibility genes and/or therapeutic targets for alcohol abuse and alcoholism in man.
