The goal of this proposal is to investigate developmental differences in ethanol responsiveness and in the biological substrates that underlie ethanol's effects. Specifically, the proposed experiments will examine the role of GABA-A receptor activity in ethanol-induced changes in anxiety in adolescent and adult BALB/cByJ and C57BL/6J mice. Initial experiments will characterize the anxiety-reducing (i.e., anxiolytic) effects of acute ethanol exposure (0, 1, 2 or 3 g/kg) in adolescent and aduit mice on three tests of anxiety-like behavior, the elevated zero-maze, the light/dark choice test, and novel object exploration (i.e., cork gnawing). After examining the behavioral effects of the GABA-A receptor antagonist, picrotoxin (0, 0.75, or 2.5 mg/kg), on the above tests, the ability of picrotoxin to attenuate or block ethanol's anxiolytic effects in adolescent and adult mice will be determined. A second series of experiments will characterize the anxiety-increasing (i.e., anxiogenic) effects of ethanol withdrawal (0 or 4 g/kg) in adolescent and adult BALB/cByJ and C57BL/6J mice (following determination of blood ethanol clearance rates). Because drugs that enhance GABA-A receptor activity, such as benzodiazepines, have been shown to attenuate withdrawal-induced increases in anxiety in adults, we will examine the ability of the benzodiazepine, diazepam (0, 1 or 2 mg/kg) to attenuate the anxiogenic effects of ethanol withdrawal in adolescent and adult mice. These experiments will provide data on anxiety-like behavior and ethanol responsiveness in adolescent animals as well as determine if behavioral differences in adolescent animals are mediated by developmental alterations in GABA-A receptor activity. Comparisons of inbred strains will permit a preliminary examination into the manner in which genetic influences on ethanol responses vary over ontogeny. It is hoped that a better understanding of ethanol's effects in adolescence will aid in the development of more effective prevention strategies or treatment for human adolescents.
Showing the most recent 10 out of 18 publications
