Chronic Cocaine Treatment Decreases Levels of the G Protein Subunits Giα and Goα in Discrete Regions of Rat Brain
Abstract
Abstract: A possible role for G proteins in contributing to the chronic actions of cocaine was investigated in three rat brain regions known to exhibit electrophysiological responses to chronic cocaine: the ventral tegmental area, nucleus accumbens, and locus coeruleus. It was found that chronic, but not acute, treatment of rats with cocaine produced a small (∼ 15%), but statistically significant, decrease in levels of pertussis toxin‐mediated ADP‐ribosylation of G iα and G oα in each of these three brain regions. The decreased ADP‐ribosylation levels of the G protein subunits were shown to be associated with 20–30% decreases in levels of their immunoreactivity. In contrast, chronic cocaine had no effect on levels of G protein ADP‐ribosylation or immunoreactivity in other brain regions studied for comparison. Chronic cocaine also had no effect on levels of G Sα or G β immunoreactivity in the ventral tegmental area and nucleus accumbens. Specific decreases in G iα and G oα levels observed in response to chronic cocaine in the ventral tegmental area, nucleus accumbens, and locus coeruleus are consistent with the known electrophysiological actions of chronic cocaine on these neurons, raising the possibility that regulation of G proteins represents part of the biochemical changes that underlie chronic cocaine action in these brain regions.
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Chronic cocaine exposure is associated with decreases in tonic D2R signaling involved in drug withdrawal, compulsive intake, and reinstatement of drug-seeking behavior.
“The same chronic cocaine exposure is associated with decreases in tonic D2R signaling, and these decreases are involved in drug withdrawal, compulsive intake, and reinstatement of drug-seeking behavior (Nestler et al 1990; Self et al 1996; Perez et al 2011; Grieder et al 2012).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Nestler et al 1990
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- Authors
- Nestler, E. J., Terwilliger, R. Z., Walker, J. R., Sevarino, K. A., & Duman, R. S.
- Affiliations
- Yale University (US)
- Corresponding author
- Nestler, Eric J.
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 1990-09
- Volume
- 55
- Issue
- 3
- Pages
- 1079-1082
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2008780733
- Cited by
- 232
- References
- 18
- Citations by year
- 2025: 1 · 2022: 2 · 2021: 2 · 2020: 2 · 2017: 2 · 2016: 1 · 2015: 1 · 2014: 3 · 2013: 3 · 2012: 5
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p50da004060-13, 1r29da005490-01a1)
- National Institute of Mental Health (MH-45481)
- National Institute on Drug Abuse (2 P50 DA04060, DA-05490)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- G protein subunits, Gi alpha, Go alpha, pertussis toxin ADP-ribosylation, ventral tegmental area, nucleus accumbens, locus coeruleus, cocaine tolerance, G protein regulation, brain regions
- MeSH terms
- Adenosine Diphosphate Ribose, Animals, Brain, Cocaine, Locus Coeruleus, Male, Nucleus Accumbens, Virulence Factors, Bordetella, Rats, Inbred Strains, Tegmentum Mesencephali, GTP-Binding Proteins, Pertussis Toxin, Rats
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