Melatonergic Receptors Mediate Reduction in Ethanol Consumption in Wistar Rats

Introduction: Ethanol consumption is a major global health concern associated with many disorders. Melatonin, a circadian neurohormone, also modulates dopamine signaling and drug-seeking behaviors central to addiction. Objective: To investigate the role of melatonergic receptors in reducing ethanol consumption and explore melatonin's therapeutic potential to overcome ethanol dependence in rats. Method: Male Wistar rats were acclimatized for 5 days, then divided into two groups: ethanol-naive (n = 6) and ethanol-exposed (n = 36). The ethanol group was given 10% ethanol (7 days), followed by limited access (27 days). On day 40, the ethanol group was divided into 6 sub-groups, receiving various treatments, including melatonin and receptor blockers (10 days). Ethanol and water consumption were measured daily. On day 49, the rats were sacrificed, and dopamine levels in the nucleus accumbens were quantified using an ELISA. Results: Both melatonin doses and naltrexone significantly reduced ethanol consumption (p < 0.05) compared to their pretreatment levels. Ethanol reduction was greater in the melatonin-treated groups than the control group (p = 0.004, p = 0.007). However, the melatonin's efficacy was blocked when coadministered with receptor antagonists, showing no significant ethanol reduction vs. control (p = 0.075 and p = 0.08). Conclusions: These findings suggest that melatonin reduces ethanol intake via specific receptor pathways, supporting its potential use in treating alcohol dependence.