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Abstract

Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol dependent patients and alcohol drinking rats [1,2]. In this study, we investigated whether the melatonergic system can be used to treat alcohol addiction. Male rats were subjected to long-term voluntary alcohol consumption with repeated abstinence phases. Circadian drinking rhythmicity and patterns were registered with high temporal resolution by a drinkometer system and analysed by Fourier analysis.We examined potential anti-relapse effect of the antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist we also tested the effect of melatonin itself. Agomelatine and melatonin administered just before the dark phase led to very similar changes on all measures of the post-abstinence drinking behaviour, suggesting that effects of agomelatine on relapse-like behaviour are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern compared to vehicle-treated rats and a reduced frequency of approaches to alcohol bottles. Melatonin given at the onset of the light phase had no effect on the circadian phase and very small effect on alcohol consumption [3]. We conclude that targeting the melatonergic system in alcohol dependent individuals can induce a circadian phase advance, which may restore normal sleep architecture and reduce relapse behaviour. This effect of melatonin may not be restricted to alcohol-related behaviours.We also showed that administration of melatonin lowered cue-induced cocaineseeking behaviour and motivation to self-administer cocaine [4].