F. Nava et al., Permissive role of dopamine D-2 receptors in the hypothermia induced by Delta(9)-tetrahydrocannabinol in rats, PHARM BIO B, 66(1), 2000, pp. 183-187
Cannabinoids produce analgesia, hypomotility, catalepsy, cognitive deficits
and positive reinforcement. Moreover, Delta(9)-tetrahydrocannabinol ((9)-T
HC) 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 De
lta(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 cannab
inoid 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 hypothermi
c effect of Delta(9)-tetrahydrocannabinol was potentiated by the D-2 dopami
ne receptor agonists (-)-quinpirole (0.025 and 0.500 mg/kg, SC) and (+)-bro
mocriptine (0.5 and 1 mg/kg, IP). In contrast, the Delta(9)-THC-induced hyp
othermic 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 permissiv
e role in the hypothermic action of cannabinoids. (C) 2000 Elsevier Science
Inc.