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 (endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1-methyl-1H-indazole-3- carboxamide hydrochloride), a selective 5-hydroxytryptamine3 (5-HT3) receptor antagonist, on the potentiation of brain stimulation reward by microinjection of 2.5 micrograms/0.25 microliters of morphine sulphate (7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol sulphate) into the ventral tegmental area. As previously reported, morphine produced a significant reduction in reward threshold without altering maximal rates of responding. Granisetron attenuated the potentiating effect of morphine at the highest dose and failed to alter reward threshold or maximal rates of responding when given alone, except at the lowest dose where a small and statistically significant increase in threshold was found. These results provide additional evidence that 5-HT3 receptor antagonists may reduce the rewarding effect of opiates and do not impair the ability to produce operant responses. The weak attenuation observed with granisetron alone suggests that 5-HT3 receptors are unlikely to constitute an important influence on the directly stimulated reward-relevant pathway(s).
Rompré
P P
PP
Centre de Biomédecine, Hôpital du Sacré-Coeur, Montréal, Québec, Canada.
Injoyan
R
R
Hagan
J J
JJ
D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D004567:Electrodes, Implanted; D017829:Granisetron / Q000008:administration & dosage / Q000494:pharmacology*; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000633:toxicity*; D051381:Rats; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013194:Staining and Labeling; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D017829:Granisetron; D009020:Morphine; D012702:Serotonin Antagonists