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

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Abstract

Anxiety and depression, key symptoms of the cocaine withdrawal syndrome in human addicts, are considered the main factors that precipitate relapse in chronic cocaine addiction. Pharmacological therapeutic strategies should 1) decrease the cocaine-reinforcing effects and 2) decrease the adverse symptoms of cocaine withdrawal. Therefore, it requires improving the effect of effective therapy (mirtazapine) through combination with other (s) effective therapies (prazosin). 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 in Wistar 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.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

This study was carried out with the support of grants INP-2040.

Funding

National Institute of Psychiatry: INP-2040.

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  1. Subdirección de Investigaciones Clínicas, Laboratorio de Neurofarmacología Conductual, Microcirugía y Terapéutica Experimental, Instituto Nacional de Psiquiatría, Ciudad de México, 14370, México

    Susana Barbosa-Méndez & Alberto Salazar-Juárez

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  1. Susana Barbosa-Méndez
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  2. Alberto Salazar-Juárez
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Participated in research design: Alberto Salazar-Juárez.

Conducted experiments: Alberto Salazar-Juárez, Susana Barbosa Méndez. Performed data analysis: Alberto Salazar-Juárez.

Wrote or contributed to the writing of the manuscript: Alberto Salazar-Juárez.

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Correspondence to Alberto Salazar-Juárez.

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Barbosa-Méndez, S., Salazar-Juárez, A. Prazosin Enhances the Effectiveness of Mirtazapine on Anxiety- and Depression-Like Behaviors in Rats during Cocaine Withdrawal. Int J Ment Health Addiction (2024). https://doi.org/10.1007/s11469-024-01247-7

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