Effects of long-term administration of haloperidol on electrophysiologic properties of rat mesencephalic neurons.

Haloperidol (1.5-1.7 mg/kg/day) was administered to rats via their drinking water for periods of either 4 weeks or 13 to 14 months, after which the animals were withdrawn from the neuroleptic for 1 or 2 weeks, respectively. Rats given haloperidol for 13 to 14 months exhibited significantly more perioral dyskinesias than controls. Single-unit extracellular recordings were obtained from the substantia nigra and ventral tegmental area in subjects under urethane anesthesia. After 1 month and after 1 year of treatment, a significant decrease in the mean firing rate of substantia nigra pars reticulata neurons was found. Subtle changes in the response of pars reticulata neurons to striatal stimulation were seen after extended haloperidol intake. No consistent effects of haloperidol administration for 4 weeks or 13 to 14 months were found for either the number of spontaneously active dopamine neurons or their firing rates. Histopathologic assessment of tissue from dorsomedial, dorsolateral and ventrolateral sectors of the striatum revealed no significant effect of long-term haloperidol treatment on neuronal cell counts. The results are discussed with reference to neuroleptic-induced tardive dyskinesias.