Ethanol priming and its effects on consumption and accumbal plasticity

Alcohol abuse and dependence are major concerns in the United States because of their chronic, detrimental health effects and societal costs. The mesocorticolimbic pathway and the nucleus accumbens (NAc), in particular, play critical roles in the formation of drug dependence and expression of drug related behaviors. The NAc contains two subregions, the core and shell, which encode different aspects of drug responding and have distinct dopamine responses. The accumbens can be further divided into two subpopulations of D1-dopamine receptor (D1) or D2-dopamine receptor (D2) expressing medium spiny neurons (MSNs) that precipitate different intracellular cascades and actions upon the reward circuitry. Alterations in the expression N-methyl-D-aspartate receptor (NMDAR)-dependent long-term depression (LTD) in the D1 MSNs of the NAc shell are seen following chronic intermittent ethanol (CIE) exposure and sustained operant responding. To our knowledge, however, LTD induction has not been extensively studied in volitional self-administration. Prior to operant training, pre-exposure of ethanol, or ethanol priming, is necessary to develop the association of the positive effects of ethanol, but it has not been shown if similar changes in LTD induction occur during this brief ethanol exposure. The purpose of this thesis is to review the current research studying alcohol and its effects on accumbal plasticity, a preview of my work depicting an ethanol-only operant self-administration protocol, and the future directions of alcohol research.