Dopamine Receptor Mediated Hypothermic Action of B-HT 920 in Rats

Abstract

Abstract The hypothermic action of the thiazoloazepine derivative B-HT 920, an α2-adrenoceptor agonist has been investigated in rats. B-HT 920 (6-allyl-2-amino-5,6,7,8-tetrahydro-4H-thiazolo-(4,5-d)-azepine dihydrochloride) (0·25–10 mg kg−1 i.p.) induced a dose-dependent hypothermia. The peak effect was seen within 60·90 min and lasted up to 120 min. Its action was potentiated by the selective D1-dopamine agonist SKF 38393 and inhibited by the D2-anatagonists haloperidol (1 mg kg−1) and sulpiride (100 mg kg−1). The hypothermic action of B-HT 920 was centrally mediated; i.c.v. administration of 10 μg produced a significant fall in rectal temperature which was sensitive to blockade by haloperidol. B-HT 920 also potentiated the hypothermic action of apomorphine (0·1 and 0·5 mg kg−1) in a haloperidol sensitive manner. Reserpine (5 mg kg−1 i.p.) pretreatment reduced the hypothermic response of B-HT 920 (0·5 mg kg−1) but sensitized the response due to the combination of B-HT 920 (0·5 mg kg−1) and apomorphine (0·1 mg kg−1). Neither the selective α2-adrenoceptor antagonists, yohimbine (1 mg kg−1) or idazoxan (1 mg kg−1), the histamine antagonist mepyramine (10 mg kg−1) nor the 5-HT antagonist cyproheptadine (5 mg kg−1) inhibited B-HT 920-induced hypothermia. Similarly, the selective α1-antagonist prazosin (1 mg kg−1) and the β-antagonist propranolol (10 mg kg−1) failed to modify the hypothermic action of B-HT 920. These observations demonstrated hypothermia induced by B-HT 920 is mediated by postsynaptic D2-receptors and D1- and D2-receptor interplay is essential for the full expression of hypothermia in rats.