Development of efficacious pharmacologic treatments for alcoholism and alcohol abuse will be facilitated by the identification of the neuropharmacological basis of ethanol's motivational effects. The central research goal of this new FIRST award application is to characterize the role of central serotonin systems in mediating the rewarding and aversive effects of ethanol. Three behavioral indices of ethanol's motivational effects will be used to determine the specific motivational effects of ethanol in combination with fluoxetine, a serotonin uptake inhibitor, quipazine, a mixed serotonin agonist, 8-OHDPAT, a serotonin 5-HT1A agonist and LY 278,584, a serotonin 5-HT3 antagonist. Serotonergic agents of these types appear to reduce ethanol drinking, yet the precise motivational mechanism underlying this action is unknown. Place conditioning will be used to characterize the influence of the serotonergic agents listed above on ethanol's direct rewarding effect and on the expression of conditioned reward to ethanol paired cues. Taste conditioning will be used to determine the influence of serotonergic agents on ethanol's aversive effect Further, the influence of serotonergic agents on acquisition and expression of ethanol discrimination will be assessed in order to determine the nature of serotonin's role in the discriminative stimulus properties of ethanol. Additional place and taste conditioning studies will determine the specificity of serotonergic modulation of ethanol's motivational effects by comparing the acquisition and expression of placed preference and taste aversion using non-drug conditioning stimuli. These experiments offer systematic characterizations of selected serotonergic agents on the motivational (rewarding and aversive) properties of ethanol. Using well developed behavioral procedures we will be able to specifically determine the rewarding and aversive efficacy of ethanol in combination with serotonergic agents that have been proposed as potential treatments for alcoholism. These experiments will provide important new information on the mechanism of ethanol's motivational effects which are often seen as critical for the development of alcoholism and alcohol abuse.
| Risinger, F O; Quick, E; Belknap, J K (2000) Quantitative trait loci for acute behavioral sensitivity to paraoxon. Neurotoxicol Teratol 22:667-74 |
