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The 5 -HT3 receptor antagonists, granisetron and ondansetron, do not affect cocaine-induced shifts in intra-cranial self-stimulation thresholds

Psychiatry Research Department, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK

P. Boyland

Psychiatry Research Department, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK

J.J. Hagan

Psychiatry Research Department, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK

The effects of the 5-HT ₃ receptor antagonists, granisetron and ondansetron, were investigated on behaviour maintained by intracranial self-stimulation (ICSS). Rats, implanted with bipolar electrodes in the lateral hypothalamus, were trained to lever press on a continuous reinforcement schedule for positively reinforcing trains of electrical stimulation. The frequency at which responding reached 50% of maximum (M50) and the maximum rate of responding (asymptote) were used to measure drug effects. Granisetron (0.01-0.1 mg/kg i.p ) and ondansetron (0.03-0.3 mg/kg i.p ) had no effect on either parameter. In contrast, cocaine (20 mg/kg i.p ) potentiated rewarded responding, reducing M50 values, but neither granisetron (0.01-3.0 mg/kg i.p ) nor ondansetron (0.03-0.3 mg/kg i.p ) blocked this effect. Neither did granisetron (0.1-10.0 mg/kg i.p ) alter the effect of lower doses of cocaine (10 mg/kg i.p.). These data suggest that 5 -HT ₃ receptors do not play a significant role in mediating responding maintained by ICSS in the rat through hypothalamic electrodes. Neither do they modulate cocaine-induced potentiation of the behaviour.

Key Words: intra-cranial self-stimulation • granisetron • ondansetron • cocaine • lateral hypothalamus • rat • reward; reinforcement

Journal of Psychopharmacology, Vol. 9, No. 4, 342-347 (1995)
DOI: 10.1177/026988119500900409


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