project proposes to continue cellular studies of the role of neurotransmitters and their receptors inalcohol drinking and dependence, and is based on behavioral findings that the central amygdala nucleus(CeA) is a key brain area involved in stress reactions and alcohol dependence. These behaviors involveseveral transmitters, including GABA, glutamate, CRF, opioids, endocannabinoids (eCBs) and neuropeptideY (NPY). With the rationale that the synapse is the most sensitive site of ethanol action, and particularlythose synapses in CeA mediated or regulated by these transmitters, we hypothesize that these sameneuropharmacological systems within the CeA are involved in excessive alcohol drinking and dependence.Therefore, we propose 3 Specific Aims to clarify the cellular underpinnings of these behaviors, using in vitroelectrophysiological recording and in vivo microdialysis in CeA neurons of 2 TSRI-ARC rat models of selfadministeredbinge drinking and chronic ethanol-induced dependence (CEID), by studying: 1) the synapticand cellular effects and interactions of opioids with CRF and acute and chronic ethanol exposure via thesebinge and dependence models. 2) the effects and interactions of cannabinoids and eCBs with CRF andacute and chronic ethanol exposure via these two models; and 3) the effects and interactions of NPY withCRF and acute ethanol in dependence, withdrawal and protracted abstinence. The electrophysiologicalstudies will use CeA brain slices and involve standard intracellular and whole-cell clamp methods and abattery of measures to assess the pre- versus postsynaptic sites of action of ethanol and ligand effects.Microdialysis will be used to verify transmitter release. This project should provide important new informationon the possible sequelae of ethanol binge drinking to dependence, at the cellular, synaptic and ion channellevels.
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