Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala

NEUROPHARMACOLOGY

卷:99

Article

Pleil, Kristen E.^1,2  Lowery-Gionta, Emily G.^1,2  Crowley, Nicole A.^1,3  Li, Chia^1,3  Marcinkiewcz, Catherine A.^1,2  Rose, Jamie H.⁴  McCall, Nora M.^1,2  Maldonado-Devincci, Antoniette M.¹  Morrow, A. Leslie^1,2  Jones, Sara R.⁴  Kash, Thomas L.^1,2 

[1] Univ N Carolina, Sch Med, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA

[2] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA

[3] Univ N Carolina, Curriculum Neurobiol, Chapel Hill, NC 27599 USA

[4] Wake Forest Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC USA

关键词: Bed nucleus of the stria terminalis;    Central amygdala;    Chronic alcohol exposure;    Limbic system;    Neuronal excitability;    Prefrontal cortex;    Synaptic transmission;    Patch-clamp electrophysiology;   

DOI  :  10.1016/j.neuropharm.2015.06.017

来源: Elsevier

【 摘 要 】

Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions. Forty-eight hours after four cycles of CIE, mice were either assayed in the marble burying test (MBT) or their brains were harvested and whole-cell electrophysiological recordings were performed in the prelimbic and infralimbic medial prefrontal cortex (PLC and ILC), the lateral and medial central nucleus of the amygdala (1CeA and mCeA), and the dorsal and ventral bed nucleus of the stria terminalis (dBNST and vBNST). Ethanol-exposed mice displayed increased anxiety in the MBT compared to air-exposed controls, and alterations in neuronal function were observed in all brain structures examined, including several distinct differences between subregions within each structure. Chronic ethanol exposure induced hyperexcitability of the ILC, as well as a shift toward excitation in synaptic drive and hyperexcitability of vBNST neurons; in contrast, there was a net inhibition of the CeA. This study reveals extensive effects of chronic ethanol exposure on the basal function of cortico-limbic brain regions, suggests that there may be complex interactions between these regions in the regulation of ethanol-dependent alterations in anxiety state, and highlights the need for future examination of projection-specific effects of ethanol in cortico-limbic circuitry. (C) 2015 Published by Elsevier Ltd.

【 授权许可】

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