Modification of the behavioural effects of haloperidol and of dopamine receptor regulation by altered thyroid status

Abstract

Rats made hypothyroid by the chronic oral administration of 200 mg/kg propylthiouracil were less sensitive to the cataleptic effects of haloperidol (0.1 mg/kg) treatment than were euthyroid rats chronically treated with isotonic saline. However, rats made hyperthyroid by the chronic injection of 200 micrograms/kg thyroxine were not more sensitive to the cataleptic suppressant effects of haloperidol (0.1 mg/kg). Higher doses of haloperidol (1 and 5 mg/kg) produced significantly greater catalepsy in the hyperthyroid rats and significantly reduced catalepsy in the hypothyroid rats. Receptor binding studies carried out on the striata from rats sacrificed 48 h after a 6-day course of chronic haloperidol (0.1 mg/kg once daily) treatment revealed a significant upregulation (increase) of dopamine receptors in the hypothyroid rats only. These findings are consistent with the hypothesis that altered thyroid status can modify the sensitivity of dopamine receptors.