The objective of the proposed studies is to investigate the influence of chronic EtOH treatment on the CRF system and the involvement of this system in the EtOH withdrawal syndrome and EtOH reward. CRF regulates hormones of the HPA axis, which aid in the preservation of homeostasis. Disruption of their normal secretion via EtOH self-administration could produce severe consequences for the organism's survival. Experiments proposed under Specific Aim 1 would advance the understanding of the neurobiological changes in the function of the extrahypothalamic CRF systems and the HPA axis resulting from chronic EtOH exposure by exploring the specific neural substrates underlying CRF regulation of the HPA axis. A major characteristic of the EtOH withdrawal syndrome is the anxiogenic-like response produced by withdrawal. Experiments proposed under Specific Aim 2 will examine the attenuation of the anxiogenic-like response to single and repeated episodes of EtOH withdrawal via antagonism of the CRF system. In addition, dependence appears to be an important factor in maintaining alcohol-seeking behavior. Since anxiety has been found to have a major influence on relapse of alcohol drinking in alcoholics, experiments outlined under Specific Aim 3 will further examine the role of CRF in mediating the rewarding properties of EtOH subsequent to dependence.
