The hypothyroid rat as a model of increased sensitivity to dopamine receptor agonists

Control and hypothyroid rats were challenged with a range of doses (0.5-4 mumol/kg) of either the nonselective dopamine agonist, apomorphine, or the selective D2 receptor agonist. LY 171555, and their stereotyped head-down sniffing (SHDS) responses measured. The dose-response curves for both agonists were shifted to the left in the hypothyroid rats compared to water-treated controls. Increasing doses of the selective D2 antagonist, raclopride, caused a parallel shift to the right in the LY 171555-induced SHDS dose-response curve. Schild analysis revealed a decreased sensitivity to raclopride in the hypothyroid animals. The selective D1 antagonist SCH 23390 was observed to decrease the maximal response elicited by LY 171555 in a dose-dependent manner and the hypothyroid rats were more sensitive to this effect. It was concluded that hypothyroid rats showed an apparent increased sensitivity to D2 receptor agonists and a decreased sensitivity to D2 antagonists. In addition, the facilitation effect of the D1 receptor on the D2 receptor appeared less tightly coupled in the hypothyroid rats.