The function of the neurotransmitter serotonin is thought to be reduced in alcoholism. Drugs such as fluvoxamine enhance synaptic serotonin levels. Thus, these drugs were thought to be potentially useful in treating alcoholism. We have conducted studies examining whether fluvoxamine can selectively suppress ethanol-maintained behavior. We found that fluvoxamine could indeed in many circumstances selectively suppress ethanol-maintained behavior (Lamb &Jarbe, 2001;Ginsburg et al 2005). However, fluvoxamine as well as other similar drugs have not proven to be effective in treating alcoholism. In part, this is likely due to the rapid tolerance that develops to these selective effects (Ginsburg &Lamb, In Press a). However, other factors also limit the utility of fluvoxamine as well as the current utility of the procedures available for identifying new alcoholism treatment medications. This is that while fluvoxamine can selectively suppress ethanol-maintained behavior in some contexts, under other contexts this selectivity is reversed (Ginsburg &Lamb, submitted). A key to developing new effective anti-alcoholism medications is the identification of compounds that suppress ethanol-maintained behavior while leaving other important behaviors intact. Thus, it is important to understand how the experimental context can change the selectivity of potential anti-alcoholism medications and how general this context-dependent selectivity is. The two specific aims of this proposal address these questions: I) Examining the behavioral mechanisms of contextual selectivity of fluvoxamine;II) Examining the pharmacological generality of contextual selectivity. Lay Summary: Identifying the behavioral mechanisms that control pharmacological selectivity for suppressing alcohol-maintained behavior and the pharmacological generality of this effect will allow us to develop better ways of seeking new treatment medications for alcoholism, new ways of better studying alcoholism in animals, and perhaps lead to better behavioral therapies for alcoholism.
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