Involvement of Serotonin Receptor Mechanisms in the Discriminative Stimulus Effects of Ketamine in Rats

We have demonstrated previously that the ketamine-induced discriminative stimulus effect is likely to reflect the phencyclidine-like psychotomimetic effects. Therefore, the present study was designed to investigate the effects of the antipsychotics and 5-HT2 receptor antagonist on the discriminative stimulus effects of ketamine in rats. While sulpiride did not attenuate the discriminative stimulus effects of ketamine, both clozapine and ketanserin attenuated those of ketamine, suggesting that the discriminative stimulus effects of ketamine are mediated by multiple receptors, especially the 5-HT2 receptor, but not the D2 receptor. Furthermore, our findings imply that atypical antipsychotics could be useful for the treatment of psychotomimetic effects induced by ketamine.