Surface expression of GABAA receptors in the rat nucleus accumbens is increased in early but not late withdrawal from extended-access cocaine self-administration
Open accessAbstract
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 GABAA 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) 6h/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 GABAA receptor subunits (α1, α2, and α4) that are strongly expressed in the NAc. We found a transient increase in surface, but not total, expression of the α2 subunit on WD2 from cocaine self-administration, an effect that was no longer observed by WD25. The expression of α1 and α4 subunits was not altered at these withdrawal times. On WD48, when AMPAR transmission is significantly potentiated, we did not find any alteration in GABAA 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 GABAA receptors.
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Withdrawal from cocaine leads to an increase in the surface expression of α2GABAARs in NAc neurons.
“Withdrawal from cocaine, on the contrary, leads to an increase in the surface expression of α2GABAARs in NAc neurons, possibly making the system even more vulnerable to the effects of cocaine and sensitization [122].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [122]
This increase may make the system more vulnerable to the effects of cocaine and sensitization.
“Withdrawal from cocaine, on the contrary, leads to an increase in the surface expression of α2GABAARs in NAc neurons, possibly making the system even more vulnerable to the effects of cocaine and sensitization [122].”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [122]
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- Authors
- Purgianto, A., Loweth, J. A., Miao, J. J., Milovanovic, M., & Wolf, M. E.
- Affiliations
- Rosalind Franklin University of Medicine and Science (US)
- Corresponding author
- Wolf, Marina E.
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 1642
- Pages
- 336-343
- ISSN
- 0006-8993 (ISSN-L)
- PMC
- PMC4899143
- OpenAlex
- W2319167265
- Cited by
- 11
- References
- 68
- Citations by year
- 2025: 1 · 2024: 1 · 2021: 3 · 2020: 1 · 2019: 1 · 2018: 2 · 2016: 2
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Rowan Digitals Works (Rowan University) (submittedVersion)
- Funders
- USPHS (DA009621, DA029099)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- GABAA receptor, nucleus accumbens, cocaine self-administration, cocaine withdrawal, medium spiny neurons, GABAA receptor subunits, alpha2 subunit, surface protein expression, cocaine craving, cocaine dependence
- MeSH terms
- Animals, Cocaine, Male, Nucleus Accumbens, Receptors, GABA-A, Self Administration, Rats, Sprague-Dawley, Protein Subunits, Rats
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