Permissive role of dopamine D2 receptors in the hypothermia induced by Δ9-tetrahydrocannabinol in rats

Cannabinoids produce analgesia, hypomotility, catalepsy, cognitive deficits and positive reinforcement. Moreover, Delta(9)-tetrahydrocannabinol ((9)-THC) and synthetic cannabinoids stimulate dopaminergic neurons and increase dopamine release in different brain areas. In order to clarify the role of endogenously released dopamine in the hypothermic response to cannabinoids, the effect of D-1 and D-2 dopamine receptor agonists and antagonists on Delta(9)-THC-induced hypothermia was studied in rats, Delta(9)-THC (2.5 and 5 mg/kg intraperitoneally [IP]) decreased body temperature in a dose-related manner. This effect was antagonized not only as expected by the CB1 cannabinoid receptor antagonist SR 141716A (0.5 mg/kg, IP) but also, unexpectedly, by the dopaminergic D-2 receptor antagonists S(-)-sulpiride (5 and 10 mg/kg, IP) and S(-)-raclopride (1 and 3 mg/kg, IP). Conversely, the hypothermic effect of Delta(9)-tetrahydrocannabinol was potentiated by the D-2 dopamine receptor agonists (-)-quinpirole (0.025 and 0.500 mg/kg, SC) and (+)-bromocriptine (0.5 and 1 mg/kg, IP). In contrast, the Delta(9)-THC-induced hypothermic effect was not modified by either by the D-1 dopamine agonist SKF 38393 (10 mg/kg SC) or by the D-1 dopamine antagonist SCH 23390 (0.5 mg/kg SC). These results suggest that the D-2 dopamine receptors have a permissive role in the hypothermic action of cannabinoids. (C) 2000 Elsevier Science Inc.