Effect of chronic amphetamine administration on central dopaminergic mechanisms in the vervet

A biochemical study of central dopaminergic mechanisms was carried out in brain tissue from vervet monkeys who had been subjected to chronic amphetamine administration. The brain concentrations of dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) were markedly reduced. Significant reductions were also observed in the activities of dopa-decarboxylase (DDC) and tyrosine hydroxylase (TH). A kinetic study of TH revealed a 60% reduction in maximum reaction velocity, consistent with destruction of DA neurones. However, homovanillic acid (HVA) concentrations were only moderately reduced, suggesting a nearly normal production of DA. Hence despite the large depletions in DA concentrations, high affinity binding of 3H-spiperone binding to striatal DA receptors was no different from controls. The results are discussed in relation to the amphetamine psychosis in humans.