title: Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala.
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.
authors.affiliation: 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.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pleil
authors.affiliation: 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.
authors.forename: Emily G
authors.initials: EG
authors.lastname: Lowery-Gionta
authors.affiliation: 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.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Crowley
authors.affiliation: 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.
authors.forename: Chia
authors.initials: C
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Marcinkiewcz
authors.affiliation: Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Jamie H
authors.initials: JH
authors.lastname: Rose
authors.affiliation: 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.
authors.forename: Nora M
authors.initials: NM
authors.lastname: McCall
authors.affiliation: Bowles Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: Antoniette M
authors.initials: AM
authors.lastname: Maldonado-Devincci
authors.affiliation: 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.
authors.forename: A Leslie
authors.initials: AL
authors.lastname: Morrow
authors.affiliation: Department of Physiology & Pharmacology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Sara R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: 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.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Kash
mesh_terms: D019973:Alcohol-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D001008:Anxiety Disorders / Q000139:chemically induced / Q000503:physiopathology; D002492:Central Nervous System Depressants / Q000633:toxicity*; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000503:physiopathology; D012686:Septal Nuclei / Q000187:drug effects / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: Bed nucleus of the stria terminalis; Central amygdala; Chronic alcohol exposure; Limbic system; Neuronal excitability; Patch-clamp electrophysiology; Prefrontal cortex; Synaptic transmission