Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol-preferring (P) rats

Zheng Ming Ding, Zachary Rodd, Eric Engleman, Jason A. Bailey, Debomoy Lahiri, William J. McBride

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The present study determined the effects of voluntary ethanol drinking and deprivation on basal extracellular glutamate concentrations and clearance in the mesolimbic system and tested the hypothesis that chronic ethanol drinking would persistently increase basal glutamate neurotransmission. Three groups of alcohol-preferring (P) rats were used: 'water group (WG),' 'ethanol maintenance group (MG; 24-hour free choice water versus 15% ethanol)' and 'ethanol deprivation group (DG; 2 weeks of deprivation).' Quantitative microdialysis and Western blots were conducted to measure basal extracellular glutamate concentrations, clearance and proteins associated with glutamate clearance. Chronic alcohol drinking produced a 70-100% increase of basal extracellular glutamate concentrations in the posterior ventral tegmental area (4.0 versus 7.0 μM) and nucleus accumbens shell (3.0 versus 6.0 μM). Glutamate clearances were reduced by 30-40% in both regions of MG rats compared with WG rats. In addition, Western blots revealed a 40-45% decrease of excitatory amino transporter 1 (EAAT1) protein, but no significant changes in the levels of EAAT2 or cystine-glutamate antiporter in these regions of MG versus WG rats. The enhanced glutamate concentrations returned to control levels, accompanied by a recovery of glutamate clearance following deprivation. These results indicated that chronic alcohol drinking enhanced extracellular glutamate concentrations in the mesolimbic system, as a result, in part, of reduced clearance, suggesting that enhanced glutamate neurotransmission may contribute to the maintenance of alcohol drinking. However, because the increased glutamate levels returned to normal after deprivation, elevated glutamate neurotransmission may not contribute to the initiation of relapse drinking.

Original languageEnglish
Pages (from-to)297-306
Number of pages10
JournalAddiction Biology
Volume18
Issue number2
DOIs
StatePublished - Mar 2013

Fingerprint

Alcohol Drinking
Glutamic Acid
Alcohols
Ethanol
Synaptic Transmission
Drinking
Water
Western Blotting
Maintenance
Antiporters
Ventral Tegmental Area
Cystine
Microdialysis
Nucleus Accumbens
Proteins
Recurrence

Keywords

  • Alcohol deprivation
  • alcohol drinking
  • alcohol-preferring (P) rats
  • glutamate neurotransmission
  • glutamate transporter
  • nucleus accumbens
  • ventral tegmental area

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health
  • Pharmacology

Cite this

Alcohol drinking and deprivation alter basal extracellular glutamate concentrations and clearance in the mesolimbic system of alcohol-preferring (P) rats. / Ding, Zheng Ming; Rodd, Zachary; Engleman, Eric; Bailey, Jason A.; Lahiri, Debomoy; McBride, William J.

In: Addiction Biology, Vol. 18, No. 2, 03.2013, p. 297-306.

Research output: Contribution to journalArticle

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