Neurochemical basis of neurotoxicity

The neurotoxic properties of 6-hydroxydopamine and 5,7-dihydroxytryptamine are reviewed. The neurochemical responses of the dopaminergic and serotonergic systems after methamphetamine (METH) are reported. METH decreased activities of tyrosine hydroxylase and tryptophan hydroxylase; concentrations of dopamine (DA) and 5-hydroxytryptamine (5HT) and their respective metabolites were decreased in parallel with the decline in activity of the enzymes. When a variety of pharmacologic or surgical procedures were used to decrease DA content prior to administration of METH, the effects of METH were attenuated. From these data it is inferred that DA is essential for the METH-induced response. 3,4-Methylenedioxymethamphetamine (MDMA) produced similar effects which were also DA-dependent. Evidence for a role of glutamate and oxidative stress in the neurotoxicity of the amphetamines is presented.