Journal article
Functional alterations in the dorsal raphe nucleus following acute and chronic ethanol exposure
Neuropsychopharmacology (New York, N.Y.), Vol.40(3), pp.590-600
02/2015
DOI: 10.1038/npp.2014.205
PMCID: PMC4289946
PMID: 25120075
Abstract
Alcoholism is a pervasive disorder perpetuated in part to relieve negative mood states like anxiety experienced during alcohol withdrawal. Emerging evidence demonstrates a role for the serotonin-rich dorsal raphe (DR) in anxiety following ethanol withdrawal. The current study examined the effects of chronic ethanol vapor exposure on the DR using slice electrophysiology in male DBA2/J mice. We found that chronic ethanol exposure resulted in deficits in social approach indicative of increased anxiety-like behavior at both 24 h and 7 days post-ethanol exposure. At 24 h post-ethanol exposure, we observed increased excitability and decreased spontaneous inhibitory transmission (inhibitory postsynaptic currents, IPSCs) in the DR. At 7 days post-ethanol exposure, we observed increased spontaneous and miniature excitatory transmission (excitatory postsynaptic currents, EPSCs). Because acute ethanol alters GABA transmission in other brain regions, we assessed the effects of ex vivo ethanol (50 mM) on miniature IPSCs (mIPSCs) in the DR 24-h post-ethanol exposure. Bath application of ethanol enhanced the amplitude of mIPSCs in cells from ethanol-naive and chronic intermittent ethanol-exposed (CIE) mice, but significantly enhanced the frequency of mIPSCs only in cells from CIE mice, suggesting that DR neurons are more sensitive to the inhibitory effects of acute ethanol following CIE. On the basis of these findings, we hypothesize that net excitation of DR neurons following chronic ethanol exposure contributes to enhanced anxiety during ethanol withdrawal, and that increased sensitivity of DR neurons to subsequent ethanol exposure may mediate acute ethanol's ability to relieve anxiety during ethanol withdrawal.
Details
- Title: Subtitle
- Functional alterations in the dorsal raphe nucleus following acute and chronic ethanol exposure
- Creators
- Emily G Lowery-Gionta - Laboratory of Molecular Neurophysiology, Department of Pharmacology, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USACatherine A Marcinkiewcz - Laboratory of Molecular Neurophysiology, Department of Pharmacology, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USAThomas L Kash - Laboratory of Molecular Neurophysiology, Department of Pharmacology, Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Resource Type
- Journal article
- Publication Details
- Neuropsychopharmacology (New York, N.Y.), Vol.40(3), pp.590-600
- Publisher
- England
- DOI
- 10.1038/npp.2014.205
- PMID
- 25120075
- PMCID
- PMC4289946
- ISSN
- 0893-133X
- eISSN
- 1740-634X
- Grant note
- P60-AA011605 / NIAAA NIH HHS U01-AA020911 / NIAAA NIH HHS R01-AA019454 / NIAAA NIH HHS F32-AA022549 / NIAAA NIH HHS R01 AA019454 / NIAAA NIH HHS T32-AA007573 / NIAAA NIH HHS F32-AA021319 / NIAAA NIH HHS P60 AA011605 / NIAAA NIH HHS F32 AA022549 / NIAAA NIH HHS
- Language
- English
- Date published
- 02/2015
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9984040282302771
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