Antipsychotic-like effect by combined treatment with citalopram and WAY 100635: involvement of the 5-HT 2C receptor

Abstract Catalepsy occurs following high dopamine (DA) D 2 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-HT 1A 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-HT 2C receptor antagonist, SB 242084, completely prevented the citalopram/WAY 100635-induced suppression of CAR indicating an involvement of the 5-HT 2C receptor. In summary, treatment with an SSRI/5-HT 1A antagonist combination might prove beneficial in psychiatric disorders with psychotic/depressive symptoms