Group I metabotropic glutamate receptor‐mediated activation of PKC gamma in the nucleus accumbens core promotes the reinstatement of cocaine seeking
Open accessAbstract
Emerging evidence indicates that type I metabotropic glutamate receptors ( mGluRs ) in the nucleus accumbens play a critical role in cocaine seeking. The present study sought to determine the role of accumbens core mGluR1 , mGluR5 and protein kinase C ( PKC ) in cocaine priming‐induced reinstatement of drug seeking. Here, we show that intra‐accumbens core administration of the mGluR1 /5 agonist DHPG (250 μM ) promoted cocaine seeking in rats. Consistent with these results, administration of an mGluR1 (50.0 μM YM 298198) or mGluR5 (9.0 μM MPEP ) antagonist directly into the accumbens core prior to a priming injection of cocaine (10 mg/kg ) attenuated the reinstatement of drug seeking. mGluR1 /5 stimulation activates a signaling cascade including PKC . Intracore microinjection of PKC inhibitors (10 μM R o 31–8220 or 30.0 μM chelerythrine) also blunted cocaine seeking. In addition, cocaine priming‐induced reinstatement of drug seeking was associated with increased phosphorylation of PKCγ , but not PKCα or PKCβII , in the core. There were no effects of pharmacological inhibition of mGluR1 , mGluR5 or PKC in the accumbens core on sucrose seeking. Together, these findings indicate that mGluR1 and mGluR5 activation in the accumbens core promotes cocaine seeking and that these effects are reinforcer specific. Furthermore, stimulation of mGluR1 and mGluR5 in the accumbens core may regulate cocaine seeking, in part, through activation of PKCγ .
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Blockade of metabotropic glutamate 1 receptors in the nucleus accumbens blocks cue-induced incubation reinstatement and cocaine-primed reinstatement, making these receptors potential therapeutic targets.
“The blockade of metabotropic glutamate 1 receptors in the nucleus accumbens blocks cue-induced incubation reinstatement and cocaine-primed reinstatement; as a result, these receptors are potential therapeutic targets.145,146”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [145]
The Results and Discussion (pages unavailable) report that blocking mGluR1 in the accumbens core attenuated cocaine-primed reinstatement. They do not establish that it blocks cue-induced incubation reinstatement; the cue-related finding discussed concerns mGluR5. The claim also overstates attenuation as complete blockade and omits the core-specific qualification: the Introduction reports no effect of mGluR1 blockade in the accumbens shell. (LLM, conf=0.88)
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Neurobiology of addiction: a neurocircuitry analysis
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- Authors
- Schmidt, H. D., Kimmey, B. A., Arreola, A. C., & Pierce, R. C.
- Affiliations
- University of Pennsylvania (US)
- Corresponding author
- Schmidt, Heath D.
- Venue
- Addiction Biology
- Publisher
- Wiley
- Published
- 2014-02-09
- Volume
- 20
- Issue
- 2
- Pages
- 285-296
- ISSN
- 1355-6215 (ISSN-L)
- 1369-1600
- PMC
- PMC4380181
- OpenAlex
- W2102988446
- Cited by
- 38
- References
- 51
- Citations by year
- 2026: 2 · 2022: 2 · 2021: 1 · 2020: 1 · 2019: 6 · 2018: 4 · 2017: 7 · 2016: 10 · 2015: 4 · 2014: 1
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Addiction Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (DA030445, DA022339, DA033641)
- 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
- metabotropic glutamate receptor 1, metabotropic glutamate receptor 5, protein kinase C gamma, nucleus accumbens core, cocaine seeking, reinstatement of drug seeking, cocaine priming, DHPG, PKC inhibitors, chelerythrine, Ro 31-8220, sucrose seeking
- MeSH terms
- Animals, Benzimidazoles, Cocaine, Glycine, Nucleus Accumbens, Phosphorylation, Protein Kinase C, Pyridines, Resorcinols, Thiazoles, Receptors, Metabotropic Glutamate, Excitatory Amino Acid Agonists, Excitatory Amino Acid Antagonists, Dopamine Uptake Inhibitors, Cocaine-Related Disorders, Rats, Protein Kinase C-alpha, Drug-Seeking Behavior, Receptor, Metabotropic Glutamate 5, Protein Kinase C beta
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