Priority CommunicationNociceptin/Orphanin FQ Blockade of Corticotropin-Releasing Factor-Induced Gamma-Aminobutyric Acid Release in Central Amygdala Is Enhanced After Chronic Ethanol Exposure
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Slice Preparation
As previously described (18, 21), we prepared CeA slices from male Sprague-Dawley rats (150–300 g; 7–9 weeks old) that were anesthetized with halothane (3%) and decapitated.
Chronic Ethanol Treatment
We used the standard ethanol inhalation method of The Scripps Research Institute Alcohol Research Center to induce ethanol dependence (Supplement 1) (20, 27). On experiment days, the chronic ethanol-treated rats were maintained in the ethanol vapor chamber until preparation of slices (under ethanol-free conditions). We
Nociceptin Reverses CRF-Induced Enhancement of GABAergic Synaptic Transmission
We recorded intracellularly from 104 CeA neurons by stimulating locally within the CeA. The mean resting membrane potential of these CeA neurons was −76.7 ± 1.3 mV with input resistance of 131.5 ± 5.8 MΩ.
In CeA neurons of naive rats, nociceptin dose-dependently reduced the mean amplitude of evoked IPSPs (Figures 1A and 1B). The lowest concentration of nociceptin tested (100 nmol/mL) produced a slight decrease in evoked IPSPs that was not statistically significant (p > .05; df = 6; t = 2.22),
Discussion
To our knowledge, there are no previous electrophysiologic studies on the interaction between the nociceptin and CRF systems on GABAergic synapses in the CeA and the influence of alcohol dependence on this interaction. Here, we find that nociceptin pretreatment blocks CRF-stimulated GABA release. Additionally, when applied subsequent to CRF, nociceptin reverses the action of CRF. The ability of nociceptin to oppose the CRF effect was stronger in ethanol-dependent rats. Our data also indicate
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