Effect of Chronic Administration of Melatonin on Ethanol Drinking in Rat Models of Chronic Voluntary Ethanol Consumption

Objective: This study is planned to examine the possible beneficial effect of chronic administration of melatonin on ethanol drinking in rat models chronic voluntary ethanol consumption. Methods: Intermittent access 10% ethanol two-bottle-choice drinking paradigm was employed in 4 groups of rats where the rats had access to ethanol on alternate days in a week and a free access to water on all day. The ethanol and water intake was recorded on each ethanol day. All rats received drug treatment (Distilled water, naltrexone, melatonin 50 mg/kg and melatonin 100 mg/kg) for 6 days continuously once they attain stable ethanol drinking pattern. The ethanol consumption on the last drinking session before the drug administration was noted as pretreatment baseline ethanol drinking value. The ethanol consumption on the first drinking session after the last dose of drug administration was noted as the post treatment value. Results: There was no change in the amount of ethanol consumption by rats in groups receiving distilled water and melatonin 50 mg/kg body weight. There was significant reduction in the ethanol consumption in rats receiving melatonin 100 mg/kg body weight and naltrexone. Comparison among different groups showed statistically significant difference between melatonin 100 mg/kg and distilled water as well as between naltrexone and distilled water. Conclusion: Melatonin at a higher dose and naltrexone has significantly reduced ethanol consumption in rats drinking high ethanol, indicating its potential use in the management of ethanol dependence. Rather ZA, Chowta MN, Bolumbu G, Ullal S, Shenoy A (2016) Effect of Chronic Administration of Melatonin on Ethanol Drinking in Rat Models of Chronic Voluntary Ethanol Consumption. Int J Drug Dev & Res 8: 018-020 Volume 8(2): 018-020 (2016)-019 Int J Drug Dev & Res ISSN: 0975-9344 available for the next 24 hours. This pattern was repeated on the 3rd day and 5th day (i.e., Wednesdays and Fridays). The placement of the ethanol bottle is alternated daily to control for place preferences. All other days the rats had unlimited access to water. The weight of each rat was measured daily to calculate the ethanol consumption in gram per kilogram of body weight of the rat. The ethanol and water intake was documented on each ethanol day. In addition, the intake of water was recorded on the water days to enable comparison of the total fluid intake between the ethanol days (ethanol+water) and the water days. Drug administrations began after the rats maintain stable baseline ethanol drinking levels. Once the stable drinking pattern is established, rats were divided into four groups (six rats in each group) randomly matching for baseline ethanol consumption. Drug administration schedule for these groups of rats is as shown in Table 1. All rats received drug treatment for 6 days continuously. During these days, the rats had three ethanol-drinking sessions. All drugs were given 1 hour before the rats are given access to ethanol and water. The ethanol consumed was measured on days 1, 3 and 5 in each group of rats. The ethanol consumption on the last drinking session before the drug administration was noted as pretreatment ethanol drinking value (baseline). The ethanol consumption on the first drinking session after the last dose of drug administration was noted as the post treatment value. Ethanol consumption was measured in g/kg body weight. The ratio of ethanol to total fluid intake (preference to ethanol over water) was calculated. Statistical Analysis Comparison of amount of ethanol consumed after the administration of the drugs with baseline value was done by using Wilcoxon signed rank test. Comparison of ethanol consumption between drug groups was done by using Mann Whitney U test. A p value less than 0.05 was considered significant.