BRAIN STIMULATION MODELS OF DRUG ABUSE

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DESCRIPTION (provided by applicant): The major long-term objective of this scientist award is to conduct research comparing young and old rat's response to opiates and cocaine. Preliminary data has suggested major differences in reward mechanisms between young and old rats. As the population grows older the number of elderly individuals with drug dependence may sharply increase; the issue, however, of drug abuse in aging has, for the most part, been ignored. There is considerable evidence that with aging there are alterations in the brain systems implicated in the mediation of the hedonic effects of abused substances. A major aspect of the proposed research will examine the functional consequences of these alterations using a number of animal models of the rewarding effects of abused substances. Specifically the abuse substances studied will be morphine, heroin and cocaine as well as specific substances that alter the relevant neurotransmitter systems that are believed involved in the rewarding effects of these abused substances. The experimental animal will be the rat and the specific models used will be drug self-administration, conditioned place preference, and brain stimulation reward. In addition the specific dopamine (DA) agonist GBR 12009 will be investigated. DA within the nucleus accumbens will be measured using in vivo micro-dialysis in aged and young animals following the administration of morphine, GBR 12909 and BSR, alone and in combination. Another area or research will to experimentally investigate basal changes in the brain that are precipitated by the presentation of environmental cues that previously had been associated with alcohol during drinking bouts in rats this model will make use of the quantitative 2-deoxy-glucose ((2-DG) Auto radiographic method of determining local cerebral metabolic rate of glucose metabolism. In addition to the research experiments it is proposed to write a historical review of the behavioral methods that have been used in the study of abused substances.