Effect of the 5-HT3 receptor antagonist ondansetron on hypothalamic self-stimulation in rats and its interaction with the CCK analogue caerulein

It is unclear whether behavioral depression and suppression of food intake by cholecystokinin (CCK) is contributed to by aversive gastrointestinal effects such as nausea. In the present study we examined the effect of a new antiemetic agent, ondansetron, a specific antagonist of 5-HT3 receptors, on suppression of variable-interval self-stimulation by the CCK analogue caerulein. Responding by rats for brain-stimulation reward is especially sensitive to CCK, and provides a convenient means of investigating this question. Caerulein (30 micrograms/kg, s.c.), injected alone, was followed by a profound (ca. 80%) reduction in the rate of self-stimulation, lasting about 30 min. Ondansetron (1.0-1000 micrograms/kg, s.c.) injected on its own had no effect on self-stimulation rate, and a 100-micrograms/kg dose did not lessen the depressant action of caerulein. The behavioural depressant effects of CCK are thus unlikely to depend on brain mechanisms for nausea and vomiting involving 5-HT3 receptors.