Self-inhibition by dopaminergic neurones: disruption by (+/-)-alpha-methyl-p-tyrosine pretreatment or anterior diencephalic lesions.

(+)-Amphetamine sulphate infused directly into the substantia nigra, pars compacta, at low rates and in low volumes and concentrations, produces a marked and prolonged inhibition of neuronal activity. This effect was significantly reduced or abolished following (+/-)-alphamethyl-p-tyrosine pretreatment or following electrolytic lesions in the diencephalon anterior to the substantia nigra. These results confirm previous reports of similar effects of such treatments on the depression of neuronal firing produced by systemically administered amphetamine. Further, our results suggest that (+/-)-alphamethyl-p-tyrosine and anterior diencephalic lesions are affecting an indirect dopaminergic inhibitory mechanism intrinsic to the substantia nigra. Such evidence may also be regarded as consistent with the view that amphetamine produces an inhibition of dopaminergic neuronal activity by affecting release of dopamine from dendrites of dopaminergic neurones, i.e. by affecting self-inhibition by dopaminergic neurones.