Changes in dopamine-mediated behaviour during one year's neuroleptic administration.
Trifluoperazine (2.5--3.5 mg/kg/day) or thioridazine (30--40 mg/kg/day) were given in the drinking water to male Wistar rats for 12 months. Initial catalepsy and inhibition of spontaneous locomotion disappeared by 3 months and thereafter. Initial inhibition of stereotypy induced by s.c. apomorphine also disappeared by 3 months to be replaced by an enhanc-d stereotypy response after 6 and 12 months' drug intake. Drug-treated animals exhibited a greatly increased incidence of spontaneous mouth movements after 12 months' intake compared with control animals. Lower doses of both drugs (trifluoperazine 0.7--0.9 mg/kg/day; thioridazine 6--8 mg/kg/day) also initially suppressed behavioural responses but by 1 month and thereafter these animals were indistinguishable from controls. At 12 months, however, these animals also exhibited an increased incidence of spontaneous mouth movements. The data demonstrate 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.
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002375:Catalepsy / Q000139:chemically induced; D004298:Dopamine / Q000502:physiology*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology; D006801:Humans; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009055:Mouth / Q000187:drug effects; D051381:Rats; D011954:Receptors, Dopamine / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D013881:Thioridazine / Q000494:pharmacology; D013997:Time Factors; D014268:Trifluoperazine / Q000494:pharmacology
D014150:Antipsychotic Agents; D011954:Receptors, Dopamine; D014268:Trifluoperazine; D013881:Thioridazine; D004298:Dopamine