The prevention of the decrease in neostriatal tryptophan hydroxylase (TPH) activity with a single dose of methamphetamine (MA) was attempted by lesioning the nigrostriatal dopaminergic projections with bilateral nigral injections of 6-hydroxydopamine (6-OHDA). The rats were injected with MA (10 mg/kg) 11 days later, and killed 3 h after the injection. The 6-OHDA lesions prevented the decrease of TPH activity in the neostriatum, while the decrease of enzyme activity was slightly attenuated in the hippocampus and unaffected in the frontal cortex. This study demonstrates: that the attenuation of TPH activity can be prevented in a selected brain area by destroying its dopaminergic afferents, and implicates central dopamine (DA), or its metabolite, in the decrease in central TPH activity observed after a single injection of MA.