Because drug abuse continues to be a major public health problem in the United States and throughout the world, it is important that research be performed to identify the factors that may predispose an individual to abuse drugs so that effective preventative or protective strategies can be developed. It is recognized that both animals and humans display striking individual differences in their addictive liability. In order to understand the factors that influence vulnerability to addiction it is necessary to develop animal models that relate biological as well as behavioral characteristics to this phenomenon. Although traditional approaches have expanded our knowledge about the addictive properties of drugs, these studies have, by their very nature, precluded the investigation of vulnerability to addiction. The proposed research is aimed at identifying neurochemical and behavioral components that are related to an individual's propensity to self-administer drugs of abuse. Specifically, three series of experiments are proposed. Because an individual's locomotor response to novelty is predictive of high rates of drug self-administration in rats (Piazza et al., 1989), experiments in Series 1 will examine this relationship using a novel self-administration choice paradigm and in vivo neurochemical measurement techniques to provide information about individual differences in the acquisition of self-administration during exposure to a range of doses of abused drugs. Experiments in Series 2 will address the generality of individual differences in predisposition toward self-administration and specifically investigate whether differences in addictive liability are simply one facet of a more general behavioral profile. These experiments will relate an animal's performance on a serial reversal task, and a sustained attention task to a subject's sensitivity to drug-self-administration. The experiments in Series 3 are aimed at investigating prenatal factors which alter dopamine receptor populations and their subsequent effects on drug self-administration. Thus, subjects will be exposed in utero to haloperidol and nicotine, and tested for their sensitivity to self-administer drugs in adulthood.
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