Ingested alcohol produces a constellation of discernible subjective effects that are believed to be the result of ethanol's actions on multiple receptor systems at a variety of neuroanatomical sites in the central nervous system. Although the behavioral paradigm of drug discrimination has been used extensively to characterize the neuropharmacological mechanisms that mediate the interoceptive cues produced by ethanol, the neuroanatomical substrates responsible for these cues have received little attention. The goal of these experiments is to identify the network of neural activity that is responsible for the perceptible interoceptive cues that are used by the animal to distinguish ethanol from water in the drug discrimination paradigm. We will first establish the pattern of functional activity in the CNS associated with the discrimination of a low dose (1 g/kg) of ethanol. The purpose of the second set of experiments is to characterize the patterns of activity produced by the administration of higher and lower doses of ethanol that produce varying degrees of ethanol-appropriate responding. Finally, we will determine the neuroanatomical substrates of the effects of drugs with actions at the GABAA receptor complex that reliably produce ethanol-like cues, as well as determine the substrates of the effects of antagonist drugs with actions at the NMDA receptor complex that reliably produce ethanol-like cues. These experiments will provide a more complete understanding of neurobiological basis of the stimulus effects of ethanol responsible for the perceptible interoceptive cues that are used by the animal to distinguish ethanol from water in the drug discrimination paradigm.
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