title: Deciphering the relationship between vulnerability to ethanol-induced behavioral sensitization and ethanol consumption in outbred mice.
abstract: Ethanol (EtOH)-induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of alcohol dependence, but its impact on alcohol abuse is not clear. EIBS development is dependent upon animal species, strain and also individual factors. We proposed here to decipher the co-expression of EIBS and EtOH intake in individual animals among outbred Swiss mice, which exhibit heterogeneity that parallels what may occur in humans. To do so, mice were exposed to a two-bottle choice with free access to water or 10% EtOH for 6 days just before and immediately after chronic intraperitoneal 2.5 g/kg ethanol injections once a day for 10 consecutive days. Based on their sensitization scores, mice were split into resistant and sensitized animals. First, we showed that individual susceptibility to EIBS is inversely correlated with voluntary EtOH consumption. Exposure to repeated EtOH during EIBS development increased subsequent EtOH intake among the entire population. Very interestingly, subsequent analyses suggested that the less the mice are sensitized the more they increase their EtOH intake; however, resistant mice were sensitive to EtOH adulteration with quinine, whereas sensitized ones maintained their EtOH intake levels, therefore exhibiting a compulsive-like drinking pattern. In addition, we showed that resistant mice do not exhibit a weaker sensitivity to the aversive properties of EtOH that may contribute to their higher level of EtOH intake compared to sensitized mice. This study confirms and extends previous data showing a deep relationship between propensity for EtOH consumption and susceptibility to EIBS in Swiss mice.
authors.affiliation: Université de Picardie Jules Verne, UFR Pharmacie, INSERM Unit ERi 24 GRAP, France.
authors.forename: Rémi
authors.initials: R
authors.lastname: Legastelois
authors.forename: Béatrice
authors.initials: B
authors.lastname: Botia
authors.forename: Fabien
authors.initials: F
authors.lastname: Coune
authors.forename: Jérôme
authors.initials: J
authors.lastname: Jeanblanc
authors.forename: Mickaël
authors.initials: M
authors.lastname: Naassila
mesh_terms: D000428:Alcohol Drinking / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D021461:Animals, Outbred Strains; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects; D003192:Compulsive Behavior; D003213:Conditioning, Psychological; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005518:Food Preferences; D007274:Injections, Intraperitoneal; D016014:Linear Models; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011803:Quinine / Q000008:administration & dosage; D012646:Self Administration; D012965:Sodium Chloride / Q000008:administration & dosage; D013045:Species Specificity
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D012965:Sodium Chloride; D011803:Quinine
keywords: Behavioral sensitization; conditioned taste aversion; ethanol; inter-individual differences; quinine adulteration; voluntary consumption