Increased dopamine metabolism in the rat neostriatum after toxic doses of d-methylamphetamine

Abstract

Rats were given repeated large doses of d-methylamphetamine ( d-MA which have been shown to destroy a fraction of nigrostriatal dopamine (DA) nerve terminals. Two to three weeks later, the synthesis of DA in the remaining neostriatal DA terminals was examined by measuring the rate of accumulation of 3,4-dihydroxyphenylalanine (DOPA) after inhibition of L-aromatic amino acid decarboxylase by 3-dihydroxybenzylhydrazine (NSD 1015). The release of DA from surviving DA terminals was also examined by measuring the steady-state level of 3,4-dihydroxyphenylacetic acid (DOPAC). Both the rate constant of the synthesis of DA and the DOPAC/DA ratio were increased in the neostriatum of rats with large depletions of neostriatal DA. These findings suggest that both synthesis and release of neostriatal DA are enhanced in rats in which d-methylamphetamine destroyed a large number of nigrostriatal DA terminals.