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Neuropharmacology. 2015 Dec;99:735-49. doi: 10.1016/j.neuropharm.2015.06.017. Epub 2015 Jul 16.

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

Author information

1
Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
2
Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Curriculum in Neurobiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
3
Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
4
Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
5
Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA; Department of Pharmacology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: thomas_kash@med.unc.edu.

Abstract

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 (lCeA 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.

KEYWORDS:

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

PMID:
26188147
PMCID:
PMC4781662
DOI:
10.1016/j.neuropharm.2015.06.017
[Indexed for MEDLINE]
Free PMC Article

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