Gene expression/CNS reinforcing actions of ethanol

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The long-range goals of this project are to better understand the neural circuitry underlying the reinforcing actions of ethanol (E) which may be linked to excessive alcohol drinking and contribute to alcohol relapse. The overall hypothesis to be tested in this proposal is that repeated self- administration of ethanol into the VTA produces alterations in gene expression within major components of the extended amygdala. Previous studies and preliminary data indicate that the VTA plays a key role in mediating reinforcement processes, different neuronal systems may be supporting reinforcement processes in the posterior compared to the anterior VTA, and the posterior VTA supports E reinforcement. The objectives of this proposal are to characterize neuronal alterations within the extended amygdala as a result of the self-administration of E into the posterior VTA. Specific Aim 1 will determine the effects of intra-cranial self-administration (ICSA) of 150 mg % E into the posterior VTA on gene expression in the nucleus accumbens shell (ACB-sh), central nucleus of the amygdala (CeA), and medial prefrontal cortex (mPFC) of inbred alcohol-preferring (iP) rats, 2 and 6 hr after completing 8 self- administration sessions. Specific Aim 2 will determine the effects of ICSA of 150 mg% E into the posterior VTA on gene expression in the ACB-sh, CeA, and mPFC of alcohol-preferring (P) rats (a) following two sessions of extinction and (b) after reinstatement of ethanol self- infusion. Specific Aim 3 will confirm key findings observed in specific aims 1 and 2 obtained with the microchip array procedure with in situ hybridization and real time PCR techniques. The results of the proposed project will provide valuable information on neuronal systems and receptors within the extended amygdala involved in mediating the rewarding properties of alcohol.