Antipsychotic-like effect of the combined treatment with escitalopram and a 5-HT1A antagonist.

Abstract

The treatment with the combination of citalopram and the 5-HT_1A antagonist, WAY-100635 has previously been reported to display antipsychotic-like effect in the conditioned avoidance response (CAR) model probably mediated through the 5-HT_2C receptor.

In the present work the antipsychotic-like effect of the combined treatment with escitalopram, the pharmacologically active enantiomer of citalopram, and WAY-100635 was further elucidated by using the CAR model, dexamphetamine-induced locomotor activity and microdialysis. 

The treatment with the combination of escitalopram (1.25 and 5.0 mg/kg s.c.) and WAY-100635 (0.2 mg/kg s.c.) was found to decrease avoidance response behaviour without affecting escape failures, decrease dexamphetamine-induced hyperactivity, and decrease both basal and dexamphetamine-induced dopamine levels in the nucleus accumbens acutely, without affecting the dopamine levels in the striatum. These effects were reversible by pre-treatment with the selective 5-HT_2C receptor antagonist SB242084. Moreover, the effects were similar to those demonstrated with WAY-163909, a selective 5-HT_2C receptor agonist. This suggests that the effects are mediated by stimulation of the 5-HT_2C receptor.

The combined treatment with escitalopram and WAY-100635 may produce an antipsychotic-like effect exhibiting fast onset and mesolimbic selectivity. The latter suggests that the extrapyramidal symptoms liability is low.