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SFN 2005 Abstracts
THE SCRIPPS RESEARCH INSTITUTE, LA JOLLA
ETHANOL-NEUROPEPTIDES INTERACTIONS AT GABA-ERGIC SYNAPSES IN RAT CENTRAL AMYGDALA
Roberto M., Schweitzer P., Madamba S.G. and Siggins G.R.
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA
Behavioral studies show that the GABAergic system in the central nucleus of the amygdala (CeA) plays a major role in the reinforcing effects of ethanol and in the anxiogenic response to ethanol withdrawal. Corticotrophin releasing factor (CRF) and nociceptin/orphanin FQ (N/OFQ) within the CeA are also implicated in regulating voluntary ethanol consumption and in the anxiogenic response to ethanol withdrawal. We have shown that 44 mM ethanol increases GABAA receptor-mediated inhibitory currents (IPSCs) in CeA neurons from both naïve and chronic ethanol treated (CET) rats, suggesting lack of tolerance for the acute effect of ethanol. Here we compared the effects of CRF and N/OFQ on IPSCs in CeA neurons from naïve and CET rats. We found that 200 nM CRF, like ethanol, significantly enhanced evoked IPSC amplitudes (to 140%, n = 9) in CeA of naïve rats, in part via presynaptic CRF1 receptors. N/OFQ (500 nM) moderately decreased IPSC amplitudes and prevented the ethanol- and CRF-induced increase of IPSCs. N/OFQ at least in part acts presynaptically because it decreases mIPSC frequencies. Interestingly, in CeA of CET rats the ability of CRF to increase IPSCs was enhanced (to 165%, n = 9) compared to naïve rats. Similarly, the N/OFQ-induced inhibition of IPSCs was increased in neurons of CET rats, indicating an enhanced sensitivity to N/OFQ. Our data support the hypothesis that chronic ethanol enhances the sensitivity of GABAergic systems in CeA to these two neuropeptides. Supported by grants from the NIAAA (AA013517-INIA Project, AA013498-INIA Project and AA-06420) and NIDA DA13658.
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