EFFECTS OF GRANISETRON, A 5-HT3 RECEPTOR ANTAGONIST, ON MORPHINE-INDUCED POTENTIATION OF BRAIN-STIMULATION REWARD

Using the curve-shift method, we studied the effects of four doses (0. 003, 0.03, 0.3 and 3 mg/kg, s.c.) of granisetron .3.1]non-3-yl)-1-meth yl-1-H-indazole-3-carboxamide hydrochloride), a selective 5-hydroxytry ptamine(3) (5-HT3) receptor antagonist, on the potentiation of brain s timulation reward by microinjection of 2.5 mu g/0.25 mu l of morphine sulphate (7,8-didehydro-4,5-epoxy-17-methylmorphinan sulphate) into th e ventral tegmental area. As previously reported, morphine produced a significant reduction in reward threshold without altering maximal rat es of responding. Granisetron attenuated the potentiating effect of mo rphine at the highest dose and failed to alter reward threshold or max imal rates of responding when given alone, except at the lowest dose w here a small and statistically significant increase in threshold was f ound. These results provide additional evidence that 5-HT3 receptor an tagonists may reduce the rewarding effect of opiates and do not impair the ability to produce operant responses. The weak attenuation observ ed with granisetron alone suggests that 5-HT3 receptors are unlikely t o constitute an important influence on the directly stimulated reward- relevant pathway(s).