THE 5-HT3 RECEPTOR ANTAGONISTS, GRANISETRON AND ONDANSETRON, DO NOT AFFECT COCAINE-INDUCED SHIFTS IN INTRACRANIAL SELF-STIMULATION THRESHOLDS

The effects of the 5-HT3 receptor antagonists, granisetron and ondanse tron, were investigated on behaviour maintained by intracranial self-s timulation (ICSS). Rats, implanted with bipolar electrodes in the late ral hypothalamus, were trained to lever press on a continuous reinforc ement schedule for positively reinforcing trains of electrical stimula tion. The frequency at which responding reached 50% of maximum (M50) a nd the maximum rate of responding (asymptote) were used to measure dru g 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, b ut 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-HT3 receptors do not play a significant role in mediating responding maintained by ICSS in the rat through hypotha lamic electrodes. Neither do they modulate cocaine-induced potentiatio n of the behaviour.