Synergistic interactions between mirtazapine and prazosin prevent the induction and expression of behavioral sensitization to cocaine in rats

Cocaine abuse and dependence are a global public health problem. To date, no effective therapy has been established to treat cocaine dependence but mirtazapine—as well as prazosin used in preclinical and clinical trials—has been shown to decrease cocaine behavioral effects. Therefore, our hypothesis...

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Bibliographic Details
Published in:Physiology & behavior 2017-10, Vol.180, p.137-145
Main Authors: Barbosa-Méndez, Susana, Matus-Ortega, Maura, Salazar-Juárez, Alberto
Format: Article
Language:English
Subjects:
5-HT receptors
Adrenergic alpha-1 Receptor Antagonists - administration & dosage
Alpha receptors
Analysis of Variance
Anesthetics, Local - toxicity
Animals
Cocaine
Cocaine - toxicity
Cocaine-Related Disorders - etiology
Cocaine-Related Disorders - prevention & control
Cocaine-Related Disorders - psychology
Dose-Response Relationship, Drug
Drug Combinations
Drug Synergism
Drug-addiction
Locomotion - drug effects
Locomotor sensitization
Male
Mianserin - administration & dosage
Mianserin - analogs & derivatives
Mirtazapine
Pharmacotherapy
Prazosin - administration & dosage
Rats
Rats, Wistar
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Summary:Cocaine abuse and dependence are a global public health problem. To date, no effective therapy has been established to treat cocaine dependence but mirtazapine—as well as prazosin used in preclinical and clinical trials—has been shown to decrease cocaine behavioral effects. Therefore, our hypothesis was that the effectiveness of mirtazapine might improve when used in combination with prazosin. This study investigated the combined effect of mirtazapine and prazosin on cocaine-induced locomotor activity impairment in rats subjected to locomotor sensitization testing. We found that chronic treatment with the mirtazapine-prazosin combination significantly improved the effect of single mirtazapine dosing on cocaine-induced locomotor activity and on the induction and expression of cocaine sensitization. These results suggest that the combined use of mirtazapine and prazosin may be a potentially effective treatment to attenuate induction and expression of locomotor sensitization to cocaine. •Daily treatment with cocaine increases the locomotor activity of rats.•The daily dosage of mirtazapine decreases cocaine-induced locomotor activity in rats.•Chronic treatment with the mirtazapine-prazosin decreases the induction and expression of cocaine sensitization.
ISSN:0031-9384
1873-507X
DOI:10.1016/j.physbeh.2017.08.017