Dopamine nerve terminal degeneration produced by high doses of methylamphetamine in the rat brain

Abstract

Numerous recent studies indicate that when amphetamines are administered continuously or in high doses, they exert long-lasting toxic effects on dopamine (DA) neurons in the central nervous system (CNS). Specifically, it has been shown that amphetamines can decrease the content of brain DA, reduce the number of synaptosomal DA uptake sites and selectively depress the in vitro activity of neostriatal tyrosine hydroxylase (TH). To date, however, anatomical evidence of DA neuronal destruction following amphetamines has not been reported. In this study, chemical methods were used in conjunction with the Fink-Heimer method which allows for the selective silver impregnation of degenerating nerve fibers, in order to determine whether methylamphetamine, a potent psychomotor stimulant often abused by man, causes actual DA neural degeneration. It has been found that methylamphetamine induces terminal degeneration along with correlative DA neurochemical deficits in the neostriatum and nucleus accumbens; furthermore, that in cresyl violet-stained sections of the substantia nigra (SN), pars compacta, and ventral tegmental area (VTA), there is no evidence of cell body loss in rats in which 50-60% of neostriatal DA terminals have been destroyed.