Research Project
6167634
APPLICANT'S ABSTRACT: Humans voluntarily self-administer alcohol without prior induction of physical dependence and will initiate and sustain self- administration of ethanol. It is also well documented that non-dependent and nonfluid or non-food deprived rats will readily self-administer ethanol over water in limited access situations and will lever press to ingest sufficient quantities to produce meaningful blood ethanol levels. In addition to the primary reinforcing effects of ethanol, environmental factors may play an important role in the establishment and continued abuse of alcohol. More specifically, stimuli (cues) in the environment can become associated with the various effects of ethanol (birth positive and negative aspects). conditioned cues have been shown to affect the strength or weakness of alcohol-seeking behavior, physiological responses, and subjective states. Typically, these studies are in investigated in post-dependent individuals. However, it is possible that the associations formed prior to dependence play an important role on future intake patterns of alcohol. The study of the motivational effects of cues associated with ethanol is therefore critical to our understanding of the factors that mediate the transition from moderate to excessive alcohol consumption. To permit such analysis, the development of sensitive and reliable animal models is required. Initial experiments will be conducted to examine the effects of cues associated with ethanol (positive reinforcement) in dependent animals. Additional studies will examine the effect of cues associated with ethanol withdrawal (i.e., conditioned withdrawal) on the development and effectiveness of these cues to mediate ethanol-seeking behavior as well as other behaviors. Finally, the stimulus specificity if the cues will be assessed to determine the "affective" status and degree of stimulus control that these conditioned stimuli exert on behavior. These studies will go far towards understanding the role of conditioning in mediating the use and abuse of alcohol. The results of these experiments will also provide a framework for future studies aimed at the neurobiological basis of the conditioned effects of ethanol. This is important given that although the neural pathways responsible for the primary reinforcing effect of ethanol overlap with those involved its conditioned effects, it is also quite likely that separate and dissociable neural mechanisms will be identified in each independent (primary vs. secondary) process.
