NEUROCHEMICAL ACTIONS OF PSYCHOTROPIC DRUGS

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This grant is addressed toward several projects relating to neurotransmitter receptors, enzymes involved in neurotransmitter disposition and drug interactions. Three areas are described in detail. One deals with phorbol ester receptors which appear to be identical with protein kinase C. Experimental approaches are proposed to identify a role of protein kinase C in synaptic transmission. Phorbol esters will be used as probes to modify the effects of neurotransmitters upon smooth muscle and to examine the role of lithium. Effects of phorbol esters will be explored upon neurotransmitter release. Autoradiographic and immunocytochemical localization of phorbol ester receptors will also be carried out. A second project deals with the actions of the neurotoxin MPTP (1-mythyl-4-phenyl-1,2,3,6,tetrayhydropyridine). MPTP induces an experimental form of Parkinson's Disease. Detailed autoradiographic maps of MPTP receptor binding sites will be obtained. Strain differences in MPTP disposition will be explored to look for correlations with strain differences in the neurotoxicity of MPTP. The relationship of MPTP binding sites to monoamine oxidase will be examined. A third project deals with calcium antagonist receptors. Different receptor binding sites for diltiazem, verapamil-like drugs and dihydropyridines will be characterized and their inter-relationships explored. Effects of calcium antagonists on synaptosomal calcium flux will be examined and interactions among calcium antagonists of different classes upon calcium flux will be evaluated. A relationship of adenylate cyclase to synaptosomal calcium flux will also be examined.