The proposed experiments build on previous work that found that a few high doses of morphine (MS) administered within a 24 to 36 hour period in the rat will result in marked oral stereotypy that can be reexpressed up to 6 months later. The experiments will determine if this MS sensitizing treatment will increase the rewarding effects of MS as measured by intracranial rewarding electrical stimulation, MS self-administration or conditioned place preference. Because changes in basal rates of glucose metabolism in the brain have been found 6 days after the high dose MS treatment, some experiments will focus on determining the duration of this effect and the role that conditioning plays in the observed changes. By the use of various antagonists, the contribution of the excitatory amino acids in the development and expression of sensitization to oral stereotypy will be determined. Parallel experiments will be carried out with cocaine. Additionally, the extent to which cross-sensitization between morphine and cocaine occurs will be studied. If these effects are related to the brain reward system, then these experiments have the potential to increase our understanding of the long- term effects of abused substances, and possibly contribute to the understanding of the neurobiology of craving. A final question regarding long-term effects will be addressed by an experiment comparing the effects of self-administered cocaine to experimenter-administered cocaine on rewarding brain stimulation. The experimental techniques to be used are brain-stimulation reward, drug self-administration, conditioned place preference, observational ratings, and the quantitative 2-deoxy-D[14C] glucose method for determining local cerebral metabolic rates for glucose.
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