Models for examining selective effects of pharmacotherapy on reinforced behaviors

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DESCRIPTION (provided by applicant): Drugs that alter behaviors maintained by ethanol to a greater extent than behaviors maintained by an alternative reinforcer are considered selective. Such selective drugs are thought to target neurobiological systems involved in ethanol reinforcement and may prdict clinical efficacy in alcoholics. However, such selective effects may instead depend more on the schedule of reinforcement than on any direct, pharmacological effect of the drug on ethanol reinforcement per se. Acamprosate, naltrexone, and ondansetron selectively reduce several measures of ethanol reinforcement in animal studies and provide long-term benefits to alcoholics. By testing the acute effects of each drug on ethanol and food maintained behaviors under several different schedules of reinforcement, the generality of selective effects on ethanol self-administration will be assessed. Effects of each drug (expressed in ED50) on responding for either food or ethanol will be assessed in terms of response rate, reinforcerment rate, and context (independent or concurrent access). These experiments will aid our interpretation of reports of selective drug treatment effects on ethanol self- administration. Results will provide information about whether selective effects of treatments on ethanol self-administration are predictive of clinical efficacy. Further, results will address whether such selective effects are due to the pharmacology of the treatments or are due to other determinants of drug effects on behavior such as baseline response rate, reinforcement rate, or context of ethanol availability. (Relevance) By testing how different drugs alter the way animals work for alcohol, scientists can better understand how alcohol works in the brain and develop better treatments for alcoholism. Yet, the degree to which the circumstances chosen for such experiments impact these results is still poorly understood. This project will use several particularly sensitive procedures to study the effects of three promising treatments for alcoholism that also seems to decrease the amount of alcohol animals work for and drink under different conditions. This project will clarify important factors involved in studies of alcohol effects and potential medications for alcoholics.