The proposed experiments are directed towards an understanding of the neurobiological substrates that subserve the acute effects of ethanol administration with a particular focus on the identification of the specific substrates that are involved in the mediation of reinforcing properties of ethanol. It is these reinforcing properties that are thought to play a role in the excessive and uncontrolled intake of alcohol in some individuals. Brain imaging methods, such as the 2-[14C]deoxyglucose method for the measurement of rates of glucose utilization and the [14C]iodoantipyrene method for the measurement of local rates of cerebral blood flow allow the visualization and quantification of localized changes in brain function associated with various physiological, behavioral, and pharmacological conditions. The proposed experiments will make use of quantitative autoradiographic brain imaging methods to characterize the neuroanatomical circuits, and pathways that mediate the effects of acute administration of alcohol in conscious, freely-moving rats. Three approaches will be used in order to identify the neuroanatomical pathways and circuits involved in various aspects of the reinforcing effects of alcohol. The first approach is to distinguish the neural events that occur soon after alcohol is administered, ascending limb of the blood alcohol curve, with which the reinforcing effects of alcohol have been associated from those neural events that occur during the descending limb. Therefore, the first goal is to map the distribution of alterations in brain activity accompanying acute ethanol treatment as a function of time since ingestion, dose, and route of administration, and to relate these changes to concentrations of ethanol in blood. The second approach is identify the differences in brain functional activity of rats genetically selected for their preference for alcohol and comparing these levels to those in non-preferring rats. The functional consequences of ethanol administration will also be examined in these genetically selected rat lines. The third approach is to investigate the reinforcing effects of ethanol directly by examining the effects of self-administered alcohol on brain functional activity. Therefore, the third goal is to visualize potential qualitative and/or quantitative differences in the effects of self-administered and passively administered alcohol on brain functional activity. These experiments will determine whether the neuroanatomical substrates that mediate the effects of voluntarily consumed ethanol are different from those that mediate the effects of passively administered alcohol. Experiments will be conducted in outbred as well as in rat lines genetically bred for alcohol preference.
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