The objectives of this project are to study the effects of currently abused drugs on enzymes involved in the regulation of biogenic amines and to determine the mechanism(s) by which the alteration of enzyme activity occurs. Methamphetamine in large, repeated doses depressed tyrosine hydroxylase activity in the corpus striatum, substantia nigra, and nucleus accumbens. Neuroleptic agents administered currently with the methamphetamine prevented this depression. The mechanism by which the effects of these drugs occur in these dopaminergic areas of the brain is currently under investigation.