Agomelatine decreases cocaine-induced locomotor sensitisation and dopamine release in rats

Abstract

Background

Agomelatine is a melatoninergic antidepressant approved to treat the major depressive disorder. Agomelatine exerts its behavioural, pharmacological, and physiological effects through the activation of MT₁ and MT₂ melatonin receptors and the blockade of 5-HT_2B and 5-HT_2C serotonin receptors. Some studies have reported that the activation of the MT₁ and MT₂ melatonin receptors decreased cocaine-induced locomotor activity and cocaine self-administration. These findings from another study showed that agomelatine decreased alcohol consumption. This study aimed to evaluate the effects of agomelatine administration on cocaine-induced behavioural (cocaine-induced locomotor activity and cocaine-induced locomotor sensitisation) and neurochemical (dopamine levels) effects.

Methods

Male Wistar rats (250–280 g) received cocaine (10 mg/kg) during the induction and expression of locomotor sensitisation. Agomelatine (10 mg/kg) was administered 30 minutes before cocaine. After each treatment, locomotor activity was recorded for 30 minutes. Dopamine levels were determined in the ventral striatum, the prefrontal cortex (PFC), and the ventral tegmental area (VTA) by high-performance liquid chromatographic (HPLC) in animals treated with agomelatine and cocaine. Luzindole (30 mg/kg) was administered to block the agomelatine effect.

Results

In this study, we found that agomelatine decreased cocaine-induced locomotor activity and the induction and expression of locomotor sensitisation. In addition, agomelatine decreased cocaine-induced dopamine levels. Luzindole blocked the agomelatine-induced decrease in the expression of locomotor sensitisation in rats.

Conclusion

Our results suggest (1) that agomelatine showed efficacy in decreasing cocaine psychostimulant effects and (2) that agomelatine can be a useful therapeutic agent to reduce cocaine abuse.

Keywords:

• Agomelatine
• cocaine
• locomotor activity
• locomotor sensitisation
• MT1 receptor

Acknowledgments

None.

Author contributions

Took part in the research design: Alberto Salazar-Juárez.

Conducted experiments: Alberto Salazar-Juárez, Susana Barbosa Méndez, and Gilberto Perez-Sánchez.

Performed data analysis: Alberto Salazar-Juárez.

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

Disclosure statement

The authors declare that there are no conflicts of interest.

Additional information

Funding

We carried out this study thanks to CONADIC from grants INP-2000-2040 and CI-IC092020.2 and support the Gonzalo Ríos Arronte Foundation.