This proposal seeks funds from the small grant program (R03) for a comprehensive autoradiographic study of the alterations in neuroamine receptor subtypes in a primate model of alcoholism. We propose to conduct these studies in animals taken from an experimental colony of Vervet monkeys (Cercopithecus aethiops) that have been previously characterized for their descriptive behaviors and alcohol preference. The Vervet or African green monkeys, which are housed in stable social groups, are drawn from a large isolated and non-endangered Caribbean population on the island of St. Kitts, W.I. Interestingly, the feral population from which these animals came has lived for 300 years in an environment of sugar cane, burned cane and fermented cane. Population screening studies indicate that 17% of the Vervet monkeys will select alcohol over vehicle alone. The Vervet monkeys which spontaneously select alcohol and drink to intoxication have advantages for the proposed chemoanatomical studies and complement the more established animal models of alcoholism. We propose to characterize baseline neurochemical markers in alcohol-selecting and control Vervets. We will utilize in vitro autoradiography to quantify the regional density of dopaminergic and serotonergic receptor subtypes. Dopaminergic and serotonergic innervation densities will be visualized by labelling dopamine and serotonin transporters in slide-mounted brain sections. The baseline neurochemical status will be compared to altered neuroreceptor regulation during the induction and alcohol withdrawal periods. Adjacent sagittal brain sections will be processed for in vitro autoradiography to demonstrate potential alterations in the affinity .and number of dopaminergic, serotonergic and beta adrenergic subtypes during the intoxication/withdrawal phase. We will attempt to correlate the neurochemical findings with blood alcohol levels and with measures of amine-aldehyde adducts in urine and brain. The proposed preclinical studies in primates which voluntarily select alcohol are designed to provide a basis for identifying the interrelated neurochemical correlates of alcohol abuse in man.
|Mash, D C; Staley, J K; Doepel, F M et al. (1996) Altered dopamine transporter densities in alcohol-preferring vervet monkeys. Neuroreport 7:457-62|