CHANGES IN DOPAMINE-MEDIATED BEHAVIOR DURING ONE YEARS NEUROLEPTIC ADMINISTRATION

Trifluoperazine (2.5-3.5 mg/kg per day) or thioridazine (30-40 mg/kg per day) were given in the drinking water to male Wistar rats for 12 mo. Initial catalepsy and inhibition of spontaneous locomotion disappeared by 3 mo. and thereafter. Initial inhibition of stereotypy induced by s.c. apomorphine also disappeared by 3 mo. to be replaced by an enhanced stereotypy response after 6 and 12 mo. drug intake. Drug-treated animals exhibited a greatly increased incidence of spontaneous mouth movements after 12 mo. intake compared with control animals. Lower doses of both drugs (trifluoperazine 0.7-0.9 mg/kg per day; thioridazine 6-8 mg/kg per day) also initially suppressed behavioral responses but by 1 mo. and thereafter these animals were indistinguishable from controls. At 12 mo. these animals also exhibited an increased incidence of spontaneous mouth movements. The data apparently demonstrates a reversal of the initial dopamine receptor-blocking properties of trifluoperazine or thioridazine to be replaced by an enhanced response of cerebral dopamine systems while animals were still continuously receiving the drug.