Mirtazapine decreased induction and expression of cocaine + nicotine-induced locomotor sensitisation in rats

Abstract

Objectives: Concurrent abuse of cocaine and nicotine is considered a public health problem. To date, no effective therapy has been known to reduce the reinforcing effects of concurrent use of cocaine and nicotine. Mirtazapine, an antagonist of the α₂-adrenoceptor and the 5-HT_2A/C and the 5-HT₃ receptors has proven effective in reducing the cocaine, nicotine and methamphetamine behavioural effects in humans and animals. Our study evaluated the effect of mirtazapine on enhancing locomotor activity during the induction and expression of locomotor sensitisation induced by a cocaine + nicotine mixture.

Methods: Wistar rats were dosed with cocaine, nicotine or cocaine + nicotine combination. Mirtazapine (30 mg/kg, i.p.) was administered during the extinction phase.

Results: Mirtazapine decreased cocaine + nicotine-induced locomotor activity and induction and expression of locomotor sensitisation. In addition, we found that co-administration of mecamylamine and mirtazapine significantly enhanced the effect of mirtazapine on cocaine + nicotine-induced locomotor activity during induction and expression of behavioural sensitisation.

Conclusions: Our results suggest that mirtazapine demonstrated efficacy in decreasing the psycho-stimulant effects of concurrent use of cocaine and nicotine.

Keywords:

• Nicotine
• cocaine
• locomotor sensitisation
• mirtazapine
• mecamylamine

Acknowledgements

None.

Statement of interest

The authors declare that there are no conflicts of interest.

Additional information

Funding

This study was carried out with the support of grants INP-2040, and those awarded by CONADIC, the Gonzalo Ríos Arronte Foundation, Merck, Sharp & Dohme/Schering-Plough Mexico and SANFER México.