Cocaine abuse is a major health problem worldwide. Treatment based on both 5-HT 2A/C and 5-HT 3 receptor antagonists attenuate not only the effects of cocaine abuse but also the incentive/motivational effect related to cocaine-paired cues.

Mirtazapine, an antagonist of postsynaptic α 2 -adrenergic, 5-HT 2A/C and 5HT 3 receptors and inverse agonist of the 5-HT 2C receptor, has been shown to effectively modify, at the preclinical and clinical levels, various behavioral alterations induced by drugs abuse. Therefore, it is important to assess whether chronic dosing of mirtazapine alters locomotor effects of cocaine as well as induction and expression of cocaine sensitization.

Our results reveal that a daily mirtazapine regimen administered for 30 days effectively induces a significant attenuation of cocaine-dependent locomotor activity and as well as the induction and expression of behavioral sensitization. These results suggest that mirtazapine may be used as a potentially effective therapy to attenuate induction and expression of cocaine-induced locomotor sensitization.