Stress may influence the intake of ethanol in humans and animals. Stress appears to predispose rodents to ingest greater amounts of ethanol. However, the relationships between the effects of stress and alcohol on the brain are not fully known. One common neural consequence of both stress and alcohol is the activation of the dopamine system in several brain areas. The areas to be examined in this proposal include the nucleus accumbens (NAc), basolateral amygdala (BLA) and ventral tegmental area (VTA). The NPc and BLA are terminal fields for dopamine neurons that mainly originate in the VTA. We will document the impact of an acutely stressful event, intermittent footshock, on the dopamine system of genetically defined mice. Then we will document the impact of chronic exposure to alcohol on the same parameters. Finally, we will administer both stress and alcohol to the mice and see how the two events interact at the level of the dopamine system We will use microdialysis in freely moving mice and cyclic voltammctry in brain slices to examine the function and dynamics of the dopamine system in detail. These experiments will be performed first on inbred """"""""alcohol-preferring"""""""" C57BL/6J mice and """"""""alcohol-avoiding"""""""" DBA/2J mice. Not only are there differences between these two strains in preference for drinking oral alcohol, but stress/anxiety measures are also different In addition, dopamine parameters will be measured in mice created by genetic mutation or recombination that have extreme phenotypic responses to stress or ethanol exposure. One known mutation that results in a high-anxiety phenotype is the knockout of the 5-HTIA receptor. We are interested in how the dopamine system in 5-HTIA knockout mice is affected by stress, ethanol, or a combination of the two by investigating several genetically different mouse strains. We hope to establish specific molecular relationships between stress and alcohol on dopamine systems in the brain.
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