Alcohol Abuse and Alcoholism pose serious health problems world-wide. Animal models have aided in our understanding of the addiction process and the development of therapeutic strategies to treat alcoholism. Two of these animal models include selective breeding for high ethanol intakes and drug discrimination procedures. We propose to use a combination of these two models to characterize potential receptor mechanisms that may predispose individuals to seek or avoid high intakes of ethanol. Sardinian alcohol-preferring (sP) and Sardinian alcohol-non preferring (sNP) rats were selectively bred for divergent ethanol drinking behavior at the University of Cagliari, Italy. The sP rats display more behaviors indicative of anxiety compared to the sNP rats, and the voluntary ethanol intake in sP rats significantly reverses their anxiogenic state, suggesting that an anxiogenic phenotype may be linked to high ethanol preference and consumption. Because it is well accepted as an assay of receptor mediated behavioral action of a drug, we propose to use drug discrimination procedures to investigate the receptor systems that are prominent in mediating ethanol's behavioral effects associated with an """"""""anxious state"""""""" in these selected lines.
Two specific aims are proposed. One is to characterize the receptor systems that mediate the discriminative stimulus effects of ethanol associated with doses that are known to be anxiolytic. The second is to characterize the """"""""anxious state"""""""" in sP and sNP rats using a PTZ discrimination. The data gathered from the present study are expected to demonstrate that the receptors involved in mediating the effects of ethanol in sP rats are related to ethanol anxiolytic effects. Furthermore, the data will provide a receptor profiling of the behavioral effects of a genetically selected line that appears to have a strong association between ethanol consumption and the relief of anxiety.
