Neurobehavioral Assessment of Ethanol Seeking and Intake in the Rat

Indiana University Indianapolis, Indianapolis IN

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Alcohol acts as a potent reinforcer in humans and in rats, and the behaviors directly involved in alcohol use can be thought of as "goal-directed", involving two distinct phases: 1) the seeking or procurement of a particular resource (appetitive behaviors), and 2) the actual direct interactions with that resource (consummatory behaviors). This project utilizes an innovative behavioral model developed to separate the initial behavior required to obtain access to alcohol from the actual alcohol self-administration. Using this model, rats drink alcohol in the 1.0 g/kg range in <6 minutes, producing pharmacologically relevant blood alcohol concentrations (40-90mg%). Moreover, we have demonstrated that this model can identify drugs that specifically affect either the seeking or the drinking component of behavior while having little to no effect on the other component of alcohol-motivated responding. Thus, this approach provides a unique opportunity to examine the factors that independently and/or cooperatively affect the seeking and consumption of alcoholic beverages. The proposed studies systematically inactivate extremely localized neuroanatomical structures postulated to be involved in alcohol-seeking and intake, and then manipulate specific neurochemical function within these regions to dissect the neurocircuitry and neurochemistry underlying alcohol-motivated behavior. Overall, the project will: 1) assess alcohol-motivated behaviors where the preponderance of research on drug-seeking has been on other drugs of abuse; 2) focus on relatively discrete brain structures where many approaches necessitate less anatomical specificity; 3) examine alcohol vs. sucrose-reinforced responding to account for the regulation of behavior that is common to palatable, caloric goal substances; 4) lay the groundwork for the extension of the examination of binge drinking to the study of alcohol dependence; and 5) procedurally separate alcohol-seeking from drinking to attempt to identify the neuroanatomical and neurochemical substrates specific and common to these behaviors. The findings from this project will inform our basic understanding of the neural circuitry underlying alcohol-motivated behavior and determine whether or not this is a common reinforcement/addiction circuit or distinct to alcohol reinforcement. Importantly, these findings will also lay the groundwork for future pharmacotherapy development that can target an individual's specific dysregulation of seeking/initiation of drinking and/or failure to control drinking once begun. [unreadable] [unreadable] [unreadable]