Journal article
Surface expression of GABA(A) receptors in the rat nucleus accumbens is increased in early but not late withdrawal from extended-access cocaine self-administration
Brain research, Vol.1642, pp.336-343
07/01/2016
DOI: 10.1016/j.brainres.2016.04.014
PMCID: PMC4899143
PMID: 27060767
Abstract
It is well established that cocaine-induced changes in glutamate receptor expression in the nucleus accumbens (NAc) play a significant role in animal models of cocaine addiction. Far less is known about cocaine-induced changes in GABA transmission, despite its importance in regulating NAc output via local interneurons and medium spiny neuron (MSN) axon collaterals (GABA 'microcircuit'). Here we investigated whether GABA(A) receptor surface or total expression is altered following an extended-access cocaine self-administration regimen that produces a time-dependent intensification (incubation) of cue induced cocaine craving in association with strengthening of AMPA receptor (AMPAR) transmission onto MSN. Rats self-administered cocaine or saline (control condition) 6 h/day for 10 days. NAc tissue was obtained and surface proteins biotinylated on three withdrawal days (WD) chosen to span incubation of craving and associated AMPAR plasticity: WD2, WD25 and WD48. Immunoblotting was used to measure total and surface expression of three GABA(A) receptor subunits (alpha 1, alpha 2, and alpha 4) that are strongly expressed in the NAc. We found a transient increase in surface, but not total, expression of the alpha 2 subunit on WD2 from cocaine self-administration, an effect that was no longer observed by WD25. The expression of alpha 1 and alpha 4 subunits was not altered at these withdrawal times. On WD48, when AMPAR transmission is significantly potentiated, we did not find any alteration in GABA(A) receptor surface or total expression. Our findings suggest that the strengthening of AMPAR-mediated glutamate transmission in the NAc is not accompanied by compensatory strengthening of GABAergic transmission through insertion of additional GABA(A) receptors. (C) 2016 Elsevier B.V. All rights reserved.
Details
- Title: Subtitle
- Surface expression of GABA(A) receptors in the rat nucleus accumbens is increased in early but not late withdrawal from extended-access cocaine self-administration
- Creators
- Anthony Purgianto - Rosalind Franklin University of Medicine and ScienceJessica A. Loweth - Rosalind Franklin University of Medicine and ScienceJulia J. Miao - Rosalind Franklin University of Medicine and ScienceMike Milovanovic - Rosalind Franklin University of Medicine and ScienceMarina E. Wolf - Rosalind Franklin University of Medicine and Science
- Resource Type
- Journal article
- Publication Details
- Brain research, Vol.1642, pp.336-343
- DOI
- 10.1016/j.brainres.2016.04.014
- PMID
- 27060767
- PMCID
- PMC4899143
- NLM abbreviation
- Brain Res
- ISSN
- 0006-8993
- eISSN
- 1872-6240
- Publisher
- Elsevier
- Number of pages
- 8
- Grant note
- K99DA038110 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission DA009621; DA029099; K99 DA038110 / USPHS; United States Department of Health & Human Services; United States Public Health Service
- Language
- English
- Date published
- 07/01/2016
- Academic Unit
- Psychiatry
- Record Identifier
- 9984296357802771
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