title: The histone deacetylase (HDAC) inhibitor valproic acid reduces ethanol consumption and ethanol-conditioned place preference in rats.
abstract: Recent evidence suggests that epigenetic mechanisms such as chromatin modification (specifically histone acetylation) may play a crucial role in the development of addictive behavior. However, little is known about the role of epigenetic modifications in the rewarding properties of ethanol. In the current study, we studied the effects of systemic injection of the histone deacetylase (HDAC) inhibitor, valproic acid (VPA) on ethanol consumption and ethanol-elicited conditioned place preference (CPP). The effect of VPA (300 mg/kg) on voluntary ethanol intake and preference was assessed using continuous two-bottle choice procedure with escalating concentrations of alcohol (2.5-20% v/v escalating over 4 weeks). Taste sensitivity was studies using saccharin (sweet; 0.03% and 0.06%) and quinine (bitter; 20 µM and 40 µM) tastants solutions. Ethanol conditioned reward was investigated using an unbiased CPP model. Blood ethanol concentration (BEC) was also measured. Compared to vehicle, VPA-injected rats displayed significantly lower preference and consumption of ethanol in a two-bottle choice paradigm, with no significant difference observed with saccharin and quinine. More importantly, 0.5 g/kg ethanol-induced-CPP acquisition was blocked following VPA administration. Finally, vehicle- and VPA-treated mice had similar BECs. Taken together, our results implicated HDAC inhibition in the behavioral and reinforcement-related effects of alcohol and raise the question of whether specific drugs that target HDAC could potentially help to tackle alcoholism in humans.
authors.affiliation: Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE.
authors.forename: Mouza
authors.initials: M
authors.lastname: Al Ameri
authors.affiliation: Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE.
authors.forename: Shamma
authors.initials: S
authors.lastname: Al Mansouri
authors.affiliation: Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE.
authors.forename: Alyazia
authors.initials: A
authors.lastname: Al Maamari
authors.affiliation: Department of Anatomy, College of Medicine & Health Sciences, United Arab Emirates University, P.O. Box 17666, Al Ain, UAE. Electronic address: amine.bahi@uaeu.ac.ae.
authors.forename: Amine
authors.initials: A
authors.lastname: Bahi
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000097:blood; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects / Q000502:physiology; D060766:Drinking Water / Q000008:administration & dosage; D000431:Ethanol / Q000008:administration & dosage / Q000097:blood; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D011803:Quinine / Q000008:administration & dosage; D017208:Rats, Wistar; D012439:Saccharin / Q000008:administration & dosage; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D055697:Taste Perception / Q000187:drug effects / Q000502:physiology; D014635:Valproic Acid / Q000494:pharmacology*
chemical_list: D002492:Central Nervous System Depressants; D060766:Drinking Water; D056572:Histone Deacetylase Inhibitors; D000431:Ethanol; D014635:Valproic Acid; D011803:Quinine; D012439:Saccharin
keywords: CPP; Ethanol; Histone deacetylase; Two-bottle choice; Valproic acid