title: Activation of Melatonin Receptors Reduces Relapse-Like Alcohol Consumption.
abstract: Melatonin is an endogenous synchronizer of biological rhythms and a modulator of physiological functions and behaviors of all mammals. Reduced levels of melatonin and a delay of its nocturnal peak concentration have been found in alcohol-dependent patients and rats. Here we investigated whether the melatonergic system is a novel target to treat alcohol addiction. Male Wistar 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 analyzed by Fourier analysis. We examined potential antirelapse effect of the novel antidepressant drug agomelatine. Given that agomelatine is a potent MT1 and MT2 receptor agonist and a 5-HT2C antagonist we also tested the effects of melatonin itself and the 5-HT2C antagonist SB242084. All drugs reduced relapse-like drinking. Agomelatine and melatonin administered at the end of the light phase led to very similar changes on all measures of the post-abstinence drinking behavior, suggesting that effects of agomelatine on relapse-like behavior are mostly driven by its melatonergic activity. Both drugs caused a clear phase advance in the diurnal drinking pattern when compared with the control vehicle-treated group 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 effects on alcohol consumption. 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 behavior.
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vengeliene
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Hamid R
authors.initials: HR
authors.lastname: Noori
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, University of Heidelberg, Mannheim, Germany.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
mesh_terms: D000081:Acetamides / Q000494:pharmacology; D000427:Alcohol Deterrents / Q000494:pharmacology; D000428:Alcohol Drinking / Q000188:drug therapy / Q000378:metabolism*; D019973:Alcohol-Related Disorders / Q000188:drug therapy / Q000378:metabolism*; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D044122:Receptor, Melatonin, MT1 / Q000819:agonists / Q000378:metabolism*; D044123:Receptor, Melatonin, MT2 / Q000819:agonists / Q000378:metabolism*; D012008:Recurrence; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D009281:Naphthalenes
chemical_list: D000081:Acetamides; D000427:Alcohol Deterrents; D000631:Aminopyridines; D007211:Indoles; D008550:Melatonin; D044122:Receptor, Melatonin, MT1; D044123:Receptor, Melatonin, MT2; D058830:Serotonin 5-HT2 Receptor Antagonists; C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; C084711:agomelatine; D009281:Naphthalenes