Rationale: In 1990, Blum and associates reported an allelic association between the D2 dopamine receptor gene and alcoholism. A Taq I restriction fragment length polymorphism (RFLP) located in the 3' flanking region of the gene was found to be more common among alcoholics (69%) than nonalcoholics (20%) [Blum et al., 1990]. This same allele (A1) has now been associated with other types of substance use [Smith et al.,1992], while another variant of the D2 receptor gene (B1 allele), located more towards the 5' region of the gene, has also been associated with alcoholism and other drug abuse [Blum, 1992]. To further clarify the role of these allelic associations in susceptibility to addiction, parameters will be developed that distinguish individuals who differ in expression of D2 alleles. Since dopamine D2 agonists have been shown to cause changes in neuroendocrine in humans [Ben-Jonathan, 1985] and to improve motor functioning and abnormalities in visual evoked potentials (VEP) in patients with Parkinson's disease [Wachtel, 1991; Bodis-Wollner et al., 1986; Onofri et al. 1986], these will be examined as possible indicators of differences in dopamine D2 allelic status. This protocol will serve two purposes. First, it will allow us to characterize changes in neuroendocrine response profile, visual evoked potential, and motor response in non-addicted individuals after administration of the dopamine D2 agonist pergolide. Second, it will allow us to test the hypothesis that individuals who differ in D2 alleles will have different patterns of responses after pergolide challenge. In the protocol, pergolide will be administered orally in low doses to normals without a history of drug dependence or recent illicit drug use, and will not be given in combination with any other drug.
