EFFECT OF 5-HT(3) RECEPTOR ANTAGONISTS ON THE DISCRIMINATIVE STIMULUSPROPERTIES OF MORPHINE IN RATS

5-HT3 receptor antagonists, e.g. MDL72222, ondansetron and ICS205-930, have been previously reported to block a morphine (1.5 mg/kg)-induced conditioned place preference in rats. This finding suggests that thes e drugs may modify the morphine discriminative stimulus which underlie s place conditioning. To study this further we have examined the effec ts of MDL72222, ondansetron and ICS205-930 against a morphine discrimi native stimulus using a two-choice, food reinforced, operant paradigm. In an attempt to provide consistency with previous place conditioning studies, a morphine training dose of 1.5 mg/kg was used in addition t o a higher 3 mg/kg dose which was studied in separate animals. Stimulu s control of behaviour was attained at both morphine training doses, t he characteristics of each being consistent with an effect at the mu o pioid receptor. Ondansetron (0.001-1 mg/kg), MDL72222 (0.1-3 mg/kg), a nd ICS205-930 (0.001-1 mg/kg) all failed to consistently antagonise th e morphine cue at both training doses, although a mild attenuation was seen in the 1.5 mg/kg group following pretreatment with an intermedia te dose of ondansetron and ICS205-930 (both 0.01 mg/kg). The present r esults therefore suggest hat 5-HT3 antagonists do not block a morphine discriminative state, at least in rats.