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Repeated Cycles of Chronic Intermittent Ethanol Exposure Leads to the Development of Tolerance to Aversive Effects of Ethanol in C 57 BL /6 J Mice
Author(s) -
Lopez Marcelo F.,
Griffin William C.,
Melendez Roberto I.,
Becker Howard C.
Publication year - 2012
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.2011.01717.x
Subject(s) - ctl* , ethanol , taste aversion , saccharin , chemistry , medicine , endocrinology , biochemistry , taste , in vitro , cytotoxic t cell
Background Repeated cycles of chronic intermittent ethanol ( CIE ) exposure lead to increased voluntary ethanol ( E t OH ) intake in C 57 BL /6 J mice. This study evaluates the development of tolerance to E t OH 's aversive effects in CIE exposure. Methods Adult male C 57 BL /6 J mice were trained to drink 15% E t OH (vs. water) in a limited access procedure and then exposed to CIE ( E t OH mice) or air (control [CTL] mice) for 5 cycles alternating with weekly access to E t OH drinking. Following the 4th CIE cycle, the aversive effects of E t OH were evaluated using a conditioned taste aversion ( CTA ) paradigm with 1% saccharin as the conditioned stimulus. Several doses of E t OH (0, 1, 2, and 3 g/kg) and L i Cl (0.4 M, 0.02 ml/g) served as unconditioned stimuli. Finally, mice underwent a 5th CIE cycle to measure blood and brain concentrations following a 2 g/kg E t OH dose. Results CIE exposure increased E t OH drinking in E t OH mice while drinking in CTL mice remained stable. The lowest E t OH dose (1 g/kg) did not induce CTA in either group, but the highest dose (3 g/kg) produced CTA in both groups (49% reduction for CTL vs. 25% reduction for E t OH ) although the group differences were not statistically significant. However, the 2 g/kg E t OH dose induced a significant aversion in CTL mice (27% reduction) but not in E t OH mice (20% increase), indicating tolerance to E t OH 's aversive effects. L i Cl caused a similar aversion in CTL and E t OH mice (50% reduction). Finally, blood and brain ethanol concentrations were not different between CTL and E t OH mice following a 2 g/kg E t OH dose. Conclusions The data indicate that CIE exposure produces tolerance to the aversive effects of 2 g/kg E t OH . This effect does not appear to be related to a learning deficit or altered E t OH pharmacokinetics. These data support the notion that tolerance to E t OH 's aversive effects may contribute to excessive E t OH drinking in E t OH ‐dependent mice.