The use and abuse of cocaine and other drugs has increased in recent years. The use has been tied to the ability of this class of drugs to produce positively reinforcing effect ie. euphoria. These properties exhibit marked across subject variability. That is, not all individuals find the drug rewarding. The reasons for this heterogeneity are not well understood but it has been suggested that some antecedent conditions exists that cause some individuals to be more sensitive than others. The identification of these antecedent conditions seems imperative if we are to institute effective programs aimed at prevention. Environmental conditions can markedly influence the propensity of rats to self-administer cocaine but not amphetamine. Thus, it was suggested that environmental conditions influence the development of specific neurochemical systems which then determine the response to specific classes of abused drugs. The present proposal extends from these initial findings. It will attempt to establish the means by which the enviromental conditions can effect the sensitivity of adult rats to the reinforcing properties of cocaine. The first section will investigate the neurochemical bases for the acquisition and maintenance of cocaine self-administration through the usage of the intravenous self-administration paradigm. The second section will address more specifically the interaction between central dopaminergic substrates and environmental conditions that predispose rats to the reinforcing properties of cocaine. The third section will test the notion that environmentally determined changes in sensitivity to cocaine can be reversed through an alternate form of environmental manipulation. The results of these studies may point to etiological and therapeutic directions for cocaine abuse.
