CRF modulates glutamate transmission in the central amygdala of naive and ethanol-dependent rats

NEUROPHARMACOLOGY

卷:125

Article

Varodayan, Florence P.¹  Correia, Diego^1,2  Kirson, Dean¹  Khom, Sophia¹  Oleata, Christopher S.¹  Luu, George¹  Schweitzer, Paul¹  Roberto, Marisa¹ 

[1] Scripps Res Inst, Dept Neurosci, SP30-1150,10550 North Torrey Pines Rd, La Jolla, CA 92037 USA

[2] Univ Fed Parana, Dept Pharmacol, BR-81531990 Curitiba, Parana, Brazil

关键词: Amygdala;    Glutamate;    Alcohol/ethanol;    CRF;    CRF receptor;    Electrophysiology;   

DOI  :  10.1016/j.neuropharm.2017.08.009

来源: Elsevier

【 摘 要 】

Corticotropin-releasing factor (CRF) signaling in the central nucleus of the amygdala (CeA) is hypothesized to drive the development of alcohol dependence, as it regulates ethanol intake and several anxiogenic behaviors linked to withdrawal. Excitatory glutamatergic neurotransmission contributes to alcohol reinforcement, tolerance and dependence. Therefore, in this study we used in vitro slice electrophysiology to investigate the effects of CRF and its receptor subtype (CRF1 and CRF2) antagonists on both evoked and spontaneous action potential-independent glutamatergic transmission in the CeA of naive and ethanol-dependent Sprague-Dawley rats. We found that CRF (25-200 nM) concentration dependently diminished evoked compound excitatory postsynaptic potentials (EPSPs), but increased miniature excitatory postsynaptic current (mEPSC) frequencies similarly in CeA neurons of both na ve and ethanol-dependent rats, indicating reduced evoked glutamatergic responses and enhanced vesicular glutamate release, respectively. This CRF-induced vesicular glutamate release was prevented by the CRN (2) antagonist (Astressin B) and the CRF1 antagonist (R121919), but not by the CRF2 antagonist (Astressin 2B). Similarly, CRF's effects on evoked glutamatergic responses were completely blocked by CRF1 antagonism, but only slightly decreased in the presence of the CRF2 antagonist. Moreover, CRF1 antagonism reveals a tonic facilitation of vesicular glutamate, whereas the CRF2 antagonism revealed a tonic inhibition of vesicular glutamate release. Collectively our data show that CRF primarily acts at presynaptic CRF1 to produce opposite effects on CeA evoked and spontaneous glutamate release and that the CRF system modulates CeA glutamatergic synapses throughout the development of alcohol dependence. (C) 2017 Elsevier Ltd. All rights reserved.

【 授权许可】

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