Antipsychotic-like effect by combined treatment with citalopram and WAY 100635: involvement of the 5-HT2C receptor.

Catalepsy occurs following high dopamine (DA) D2 blockade by typical antipsychotic drugs (APDs). We showed that a combination of a high dose of citalopram, a selective serotonin reuptake inhibitor (SSRI) and the selective 5-HT1A receptor antagonist WAY 100635 produces significant catalepsy in rats, similar to APDs. Here, we investigated the potential antipsychotic activity of lower doses of citalopram+WAY 100635, using the conditioned avoidance response (CAR) test. Cataleptogenic liability of the combination was evaluated with the catalepsy test. Citalopram and WAY 100635 in combination, but not when given alone, produced a significant antipsychotic action in CAR without significant catalepsy, similar to the effect of a low dose of the typical APD haloperidol. Pretreatment with a selective 5-HT2C receptor antagonist, SB 242084, completely prevented the citalopram/WAY 100635-induced suppression of CAR indicating an involvement of the 5-HT2C receptor. In summary, treatment with an SSRI/5-HT1A antagonist combination might prove beneficial in psychiatric disorders with psychotic/depressive symptoms.