Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport

Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol-dependent mice and that pharmacologically manipulating glutamate...

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Main Authors:	Griffin, William C., Ramachandra, Vorani S., Knackstedt, Lori A., Becker, Howard C.
Format:	Online
Language:	English
Published:	Frontiers Media S.A. 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337330/

id	pubmed-4337330
recordtype	oai_dc
spelling	pubmed-43373302015-03-09 Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport Griffin, William C. Ramachandra, Vorani S. Knackstedt, Lori A. Becker, Howard C. Pharmacology Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol-dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point. Extracellular glutamate was measured using quantitative microdialysis procedures. Glutamate transport capacity was measured under Na+-dependent and Na+-independent conditions to determine whether the function of excitatory amino acid transporters (also known as system XAG) or of system Xc– (glial cysteine–glutamate exchanger) was influenced by CIE exposure. The results of the quantitative microdialysis experiment confirm increased extracellular glutamate (approximately twofold) in the NAc of CIE exposed mice (i.e., ethanol-dependent) compared to non-dependent mice in the NAc, consistent with earlier work. However, the increase in extracellular glutamate was not due to altered transporter function in the NAc of ethanol-dependent mice, because neither Na+-dependent nor Na+-independent glutamate transport was significantly altered by CIE exposure. These findings point to the possibility that hyperexcitability of cortical–striatal pathways underlies the increases in extracellular glutamate found in the ethanol-dependent mice. Frontiers Media S.A. 2015-02-23 /pmc/articles/PMC4337330/ /pubmed/25755641 http://dx.doi.org/10.3389/fphar.2015.00027 Text en Copyright © 2015 Griffin, Ramachandra, Knackstedt and Becker. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Griffin, William C. Ramachandra, Vorani S. Knackstedt, Lori A. Becker, Howard C.
spellingShingle	Griffin, William C. Ramachandra, Vorani S. Knackstedt, Lori A. Becker, Howard C. Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport
author_facet	Griffin, William C. Ramachandra, Vorani S. Knackstedt, Lori A. Becker, Howard C.
author_sort	Griffin, William C.
title	Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport
title_short	Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport
title_full	Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport
title_fullStr	Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport
title_full_unstemmed	Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport
title_sort	repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport
description	Repeated cycles of chronic intermittent ethanol (CIE) exposure increase voluntary consumption of ethanol in mice. Previous work has shown that extracellular glutamate in the nucleus accumbens (NAc) is significantly elevated in ethanol-dependent mice and that pharmacologically manipulating glutamate concentrations in the NAc will alter ethanol drinking, indicating that glutamate homeostasis plays a crucial role in ethanol drinking in this model. The present studies were designed to measure extracellular glutamate at a time point in which mice would ordinarily be allowed voluntary access to ethanol in the CIE model and, additionally, to measure glutamate transport capacity in the NAc at the same time point. Extracellular glutamate was measured using quantitative microdialysis procedures. Glutamate transport capacity was measured under Na+-dependent and Na+-independent conditions to determine whether the function of excitatory amino acid transporters (also known as system XAG) or of system Xc– (glial cysteine–glutamate exchanger) was influenced by CIE exposure. The results of the quantitative microdialysis experiment confirm increased extracellular glutamate (approximately twofold) in the NAc of CIE exposed mice (i.e., ethanol-dependent) compared to non-dependent mice in the NAc, consistent with earlier work. However, the increase in extracellular glutamate was not due to altered transporter function in the NAc of ethanol-dependent mice, because neither Na+-dependent nor Na+-independent glutamate transport was significantly altered by CIE exposure. These findings point to the possibility that hyperexcitability of cortical–striatal pathways underlies the increases in extracellular glutamate found in the ethanol-dependent mice.
publisher	Frontiers Media S.A.
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337330/
_version_	1613191460450992128

Repeated cycles of chronic intermittent ethanol exposure increases basal glutamate in the nucleus accumbens of mice without affecting glutamate transport

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