Discrete cell gene profiling of ventral tegmental dopamine neurons after acute and chronic cocaine self-administration
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Chronic cocaine administration induces a number of biochemical alterations within the mesolimbic dopamine system that may mediate various aspects of the addictive process such as sensitization, craving, withdrawal, and relapse. In the present study, rats were allowed to self-administer cocaine (0.5 mg/infusion) for 1 or 20 days. Tyrosine hydroxylase immunopositive cells were microdissected from the ventral tegmental area (VTA) using laser capture microdissection, and changes in the abundances of 95 mRNAs were assessed using cDNA macroarrays. Five GABA-A receptor subunit mRNAs (alpha4, alpha6, beta2, gamma2, and delta) were down-regulated at both 1 and 20 days of cocaine self-administration. In contrast, the catalytic subunit of protein phosphatase 2A (PP2alpha), GABA-A alpha1, and Galphai2 were significantly increased at both time points. Additionally, calcium/calmodulin-dependent protein kinase IIalpha mRNA levels were increased initially followed by a slight decrease after 20 days, whereas neuronal nitric-oxide synthase mRNA levels were initially decreased but returned to near control levels by day 20. These results indicate that alterations of specific GABA-A receptor subtypes and other signal transduction transcripts seem to be specific neuroadaptations associated with cocaine self-administration. Moreover, as subunit composition determines the functional properties of GABA-A receptors, the observed changes may indicate alterations in the excitability of dopamine transmission underlying long-term biochemical and behavioral effects of cocaine.
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Increases in VTA α1GABAAR expression parallel behavioral sensitization to the effects of nicotine and cocaine.
“On the contrary, chronic nicotine [118] or cocaine [119] increases VTA α1GABAAR expression, paralleling behavioral sensitization to the effects of these drugs.”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [119]
Chronic cocaine increases VTA α1GABAAR expression.
“On the contrary, chronic nicotine [118] or cocaine [119] increases VTA α1GABAAR expression, paralleling behavioral sensitization to the effects of these drugs.”
From An emerging circuit pharmacology of GABAA receptors (2018) · cites this paper as [119]
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An emerging circuit pharmacology of GABAA receptors
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- Authors
- Backes, E., & Hemby, S. E.
- Affiliations
- Emory University (US)
- ORCID
- Hemby, Scott E.
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 2003-11
- Volume
- 307
- Issue
- 2
- Pages
- 450-459
- ISSN
- 0022-3565 (ISSN-L)
- PMC
- PMC4048547
- OpenAlex
- W2118268516
- Cited by
- 48
- References
- 67
- Citations by year
- 2024: 1 · 2022: 1 · 2020: 1 · 2018: 3 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 1
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (R01DA013234, DA13234, R01DA013772, DA13772)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Keywords
- cocaine self-administration, ventral tegmental area, dopaminergic neurons, GABAA receptor subunits, tyrosine hydroxylase, PP2A catalytic subunit, Gαi2, CaMKIIα, neuronal nitric oxide synthase, gene expression profiling, neural adaptation, mesolimbic dopamine system, cocaine dependence, neuronal excitability
- MeSH terms
- Animals, Cocaine, Dopamine, Male, Neurons, Receptors, GABA-A, RNA, Messenger, Self Administration, Rats, Sprague-Dawley, Ventral Tegmental Area, Glutamic Acid, Dopamine Uptake Inhibitors, Gene Expression Profiling, Rats
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