The proposed research is committed to the further understanding of the neuronal bases of dependence to the abused opiates and cocaine. Previous work has indicated that there are protracted effects weeks after the last of a few high doses of morphine, therefore focus will be on the elucidation of these changes with cocaine as well as opiates using the quantitative 2-deoxy-D-[l-14C]glucose (2-DG) for the determination of local cerebral metabolic utilization of glucose. Because these effects were enhanced by conditioned drug cues the proposed experiments will explore in detail the effects of these conditioned cues on the protracted effects. In addition, experiments will be carried out to determine the role of the excitatory amino acids on the expression of these protracted drug effects as well as the role of GABA, adenosine, dopamine Dl receptor, and cyclic AMP systems in modulating the rewarding effects and intake of both cocaine and heroin. The experiments, taken together, will allow for the further understanding of the role of the brain reward system in mediating both the acute and protracted effects of abused substances. These protracted effects, present long after cessation of drug administration, have major importance for the understanding of the phenomenon of craving. With this knowledge effective therapies may be rationally developed. In addition to the 2-DG procedure the experiments will employ drug self- administration, brain-stimulation reward, and conditioned place preference, all models used to study the rewarding effects of abused substances. The experimental animal will be the rat.
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