Mirtazapine-induced decrease in cocaine sensitization is enhanced by environmental enrichment in rats

Several studies have reported that mirtazapine attenuated the induction and expression of cocaine-induced locomotor sensitization. Animals placed in enriched housing environments have shown a decrease in cocaine-induced locomotor activity and sensitization. In addition, it has been suggested that a pharmacological treatment combined with a behavioral intervention increases the efficacy of the former. Thus, the objective of this study was to determine if dosing of mirtazapine in an enriched housing environment enhanced the mirtazapine-induced decrease on the induction and expression of cocaine-induced locomotor sensitization. Wistar male rats were dosed with cocaine (10 mg/kg, i.p.). During the drug-withdrawal phase, mirtazapine (30 mg/kg, i.p.) was administered under standard and enriched housing environmental conditions. The environmental enrichment consisted of housing the animals in enclosures with plastic toys, tunnels, and running wheels. After each administration, locomotor activity for each animal was recorded for 30 min. The study found that treatment with mirtazapine in an enriched housing environment produced an enhanced and persistent attenuation of the induction and expression of cocaine-induced locomotor sensitization. Additionally, it reduced the duration of cocaine-induced locomotor activity in the expression phase of locomotor sensitization. Dosing of mirtazapine in an enriched housing environment enhanced the effectiveness of mirtazapine to decrease cocaine-induced locomotor sensitization. This suggests the potential use of enriched environments to enhance the effect of mirtazapine. •Mirtazapine decreases the induction and expression of cocaine-induced locomotor sensitization in male rats.•EE decreases the expression of cocaine locomotor sensitization in rats.•Mirtazapine + EE enhance the decreases the expression of cocaine locomotor sensitization in rats.