Ethanol Sensitization, Reward, and Aversion

Lessov-Schlaggar, Christina

Abstract

Repeated administration of low ethanol (EtOH) doses may lead to a progressive increase in the motor stimulant effects of EtOH, or behavioral sensitization. The lasting nature of EtOH sensitization points to neural alterations in sensitivity which may effectively maintain EtOH taking behavior leading to EtOH abuse. This proposal aims at investigating the nature of the neural adaptations through molecular and behavioral genetic approaches. First, four quantitative trait loci (QTLs) for EtOH sensitization, identified in a panel of BXDRI strains, will be verified in an F2 intercross of C57BL/6J(B6) and DBA/2J(D2) inbred strains. Four hundred F2 mice will be phenotyped for EtOH sensitization. The most and least sensitized 46 mice will be genotyped for B6 or D2 alleles at each of the four QTLs. Significant associations between the genotype and the phenotype will be statistically identified. Second, the influence of EtOH sensitization on sensitivity to EtOH reinforcement as measured by EtOH two-bottle preference will be examined in 3 mouse genotypes. A difference in EtOH consumption between sensitized mice and nonsensitized controls would imply an effect of EtOH sensitization on EtOH reinforcement efficacy. Third, the influence of EtOH sensitization on sensitivity to EtOH aversion will be examined in a genetically heterogeneous population of mice. EtOH aversion will be assessed using the conditioned taste aversion paradigm. Paring the presentation of 0.2M NaCl flavored solution with one of 3 EtOH or 3 LiCl doses will condition an aversion to the taste of the previously palatable NaC1 solution. Aversion will be evident as a decrease in NaC1 consumption over conditioning trials. This measure will be compared between sensitized and nonsensitized groups. These studies will set the groundwork for future investigation into the utility of EtOH sensitization as an important phenotype in EtOH abuse.