NEUROBIOLOGY OF TROPANE ANALOG

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Project 11 is a coordinated drug discover program that involves the full range of analytical capabilities represented within the Center. It is a continuation of the collaborative efforts of many laboratories that were previously grouped under a general core structure. The novel tropane analogs produced by the vinylcarbenoid chemistry of Dr. Huw Davies will be screened for their neurochemical potency, specificity and behavioral actions in an effort to identify compounds with scientifically interesting properties and/or therapeutic value. Compounds will be screened for their specificity and efficacy at monoamine transporters and for their lipophilicity by Drs. Childers and Bennett. Selected compounds will be characterized for their effects on regional glucose metabolism in Dr. Porrino's laboratory; she will also assess the locomotor stimulant effects on these tropanes and determine their time course. Dr. Smith will examine the effects of selected tropanes on extracellular dopamine and serotonin levels through microdialysis studies. Self-administration studies conducted by Dr. Roberts will examine the relative reinforcing efficacy of specific tropane analogues that will be useful for the analysis of basic neurobiological questions concerning psychostimulant reinforcement and as potential therapeutic targets.