Abstract

The effects of amphetamine, various phenothiazines and haloperidol on dopaminergic neurons in the substantia nigra and ventral tegmental area of the rat midbrain were studied in anesthetized and gallamine-paralyzed animals using a single unit recording technique. d-Amphetamine administered intravenously markedly decreased the spontaneous activity of dopaminergic neurons in the substantia nigra and ventral tegmental area. Antipsychotic phenothiazines and haloperidol increased the firing rate of these cells and reversed the d-amphetamine depression. Promethazin. a phenothiazine lacking antipsychotic efficacy, had no effect. In an experiment designed to correlate changes in firing rate with dopamine metabolism, neostriatal 3,4-dihydroxyphenylacetic acid concentrations were determined before and after administration of chlorpromazine (1.25 mg/kg), amphetamine (1.25 mg/kg) and promethazine (10 mg/kg). Neostriatal 3,4-dihydroxyphenylacetic acid was inceased by chlorpromazine,decreaed by amphetamine and unchanged by promethazine, thus paralleling the effects of these drugs on dopaminergic unit activity. These findings, together with our single unit recording results, are compatible with the neuronal feedback hypothesis orignally suggested as a mechanism by which these drugs might alter dopamine metabolism.