Neurobehavioral Assessment of Ethanol Seeking and Intake

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DESCRIPTION (provided by applicant): This project adopts a multidisciplinary approach, combining behavioral analyses and neuroscience techniques, to determine factors that regulate alcohol consumption and to prepare the applicant for a research career that integrates different fields of study. Alcohol consumption can be conceptualized as involving two phases of behavior. First, some level of motivation or "Craving" is reached that makes it likely that a person will seek out alcohol. Second, once the drinking has begun, added factors determine how much will be consumed in that drinking bout. Both phases of behavior contribute to the overall regulation of alcohol intake: the first determines the timing and frequency of consumption and the second determines the amount of alcohol intake at each time. Animal models currently in use primarily focus on the second phase of behavior. The proposed research makes use of a newly developed behavioral paradigm that separates alcohol seeking from self-administration. The first specific Aim of this project is to continue to characterize these two behaviors in this model. First, the effects of solution composition on the two types of behavior will be assessed by manipulating the concentrations of the ethanol and sucrose solutions that are presented. Second, the importance of the current motivational state of the animal in terms of the amount of solution already ingested will be measured by varying the amount of sucrose or ethanol administered prior to an opportunity to seek and consume additional solution. Aim 1 will employ a behavioral approach to understanding ethanol self-administration behavior and builds upon the current skills of the applicant. Aim 2 of the project is to assess the role of serotonin in the mesocorticolimbic circuitry as it affects the two phases of drinking behavior in this model. It is hypothesized that alterations in serotonin activity affect ethanol-directed behaviors via projections from the dorsal raphe, the location of the main serotonin-containing cell bodies, to the ventral tegmental area (VTA) and the nucleus accumbens. Aim 2 uses site-specific microinjections into the dorsal raphe, the VTA and the nucleus accumbens and the administration of serotonin IA and IB agonists to determine the role of this serotonin input in the control of ethanol drinking. This series of experiments makes up the majority of the project, and will involve extensive training for the applicant in the pharmacology and neuroscience of alcohol self-administration. The project as a whole will allow for an integrated approach to the analysis of alcohol consumption: the comparison of behaviors that result from manipulations of solution composition, the motivational state of the subjects and underlying neural mechanisms.