Prazosin Enhances the Effectiveness of Mirtazapine on Anxiety- and Depression-Like Behaviors in Rats during Cocaine Withdrawal

This study sought to determine whether chronic dosing of mirtazapine plus prazosin during cocaine withdrawal reduced depression- and anxiety-like behaviors that characterize cocaine withdrawal inWistar rats. Cocaine-pre-treated Wistar rats were subjected to a 60-day cocaine withdrawal period during which depression- and anxiety-like behaviors were evaluated in open field tests (OFT), the elevated plus-maze (EPM), the light –dark box test (LDT), the forced swimming test (FST), and spontaneous locomotor activity (SLA). We found 1) that chronic dosing of mirtazapine (30 mg/kg) + prazosin (1 mg/kg) decreased depression- and anxiety-like behaviors induced by 10 mg/kg of cocaine during the 60-day cocaine withdrawal . 2) prazosin enhanced the effect of mirtazapine on depression- and anxiety-like behaviors and 3) oxymetazoline blocked the prazosin-induced effect. Our results suggest that the pharmacological effect of mirtazapine on its target sites of action (α2-adrenergic and 5-HT1, 5-HT2A and 5-HT3 receptors) and of prazosin ( α1-adrenergic) within the brain may improve depression- and anxiety-like behaviors for long periods. Therefore, the findings support the use of a combination of mirtazapine  + prazosin as a potentially effective therapy to reduce anxiety and depressive-like behavior during cocaine withdrawal.
Source: International Journal of Mental Health and Addiction - Category: Addiction Source Type: research