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Pharmacol Rep. 2012;64(6):1391-9.

Effect of co-treatment with fluoxetine or mirtazapine and risperidone on the active behaviors and plasma corticosterone concentration in rats subjected to the forced swim test.

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Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland.



Several clinical reports have postulated a beneficial effect of the addition of a low dose of risperidone to the ongoing treatment with antidepressants in treatment-resistant depression.


The present study aimed to examine the effect of treatment with fluoxetine or mirtazapine, given separately or jointly with risperidone, on active behavior and plasma corticosterone level in male Wistar rats subjected to the forced swim test (FST).


The obtained results showed that fluoxetine (5 mg/kg), mirtazapine (5 and 10 mg/kg) or risperidone (0.05 and 0.1 mg/kg) did not change the active behavior of rats in the FST. However, co-treatment with fluoxetine (10 mg/kg) and risperidone (0.1 mg/kg) induced an antidepressant-like effect in that test because it significantly increased the swimming time and decreased the immobility time, while combined treatment with mirtazapine at 5 and 10 mg/kg and risperidone at 0.05 and 0.1 mg/kg evoked a significant increase in the swimming time and also climbing, and decreased the immobility time. WAY 100635 (a 5-HT(1A) receptor antagonist) at a dose of 0.1 mg/kg inhibited the antidepressant-like effect induced by co-administration of fluoxetine or mirtazapine and risperidone. Active behavior in that test did not reflect an increase in general activity, since combined treatment with fluoxetine or mirtazapine and risperidone failed to enhance the exploratory activity of rats. Co-treatment with fluoxetine or mirtazapine and risperidone did not reduce the stress-induced increase in plasma corticosterone concentration in animals subjected to the FST.


The obtained results indicate that risperidone applied in a low dose enhances the antidepressant-like activity of fluoxetine and mirtazapine in the FST (but does not normalize the stress-induced increase in corticosterone level in these rats), and that 5-HT(1A) receptors may play some role in these effects.

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