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Group I mGluR Activation Reverses Cocaine-Induced Accumulation of Calcium-Permeable AMPA Receptors in Nucleus Accumbens Synapses via a Protein Kinase C-Dependent Mechanism
The Journal of Neuroscience (2011)
  • James E. McCutcheon, Rosalind Franklin University of Medicine and Science
  • Jessica A. Loweth, Rowan University School of Osteopathic Medicine
  • Kerstin A. Ford, Rosalind Franklin University of Medicine and Science
  • Michela Marinelli, University of Texas at Austin
  • Marina E. Wolf, Rosalind Franklin University of Medicine and Science
  • Kuei Y. Tseng, Rosalind Franklin University of Medicine and Science
Abstract
Following prolonged withdrawal from extended access cocaine self-administration in adult rats, high conductance Ca2+ -ermeable AMPA receptors (CP-AMPARs) accumulate in nucleus accumbens (NAc) synapses and mediate the expression of "incubated" cue-induced cocaine craving. Using patch-clamp recordings from NAc slices prepared after extended access cocaine self-administration and >45 d of withdrawal, we found that group I metabotropic glutamate receptor (mGluR) stimulation using 3,5-dihydroxyphenylglycine (DHPG; 50 μm) rapidly eliminates the postsynaptic CP-AMPAR contribution to NAc synaptic transmission. This is accompanied by facilitation of Ca2+ -impermeable AMPAR (CI-AMPAR)-mediated transmission, suggesting that DHPG may promote an exchange between CP-AMPARs and CI-AMPARs. In saline controls, DHPG also reduced excitatory transmission but this occurred through a CB1 receptor-dependent presynaptic mechanism rather than an effect on postsynaptic AMPARs. Blockade of CB1 receptors had no significant effect on the alterations in AMPAR transmission produced by DHPG in the cocaine group. Interestingly, the effect of DHPG in the cocaine group was mediated by mGluR1 whereas its effect in the saline group was mediated by mGluR5. These results indicate that regulation of synaptic transmission in the NAc is profoundly altered after extended access cocaine self-administration and prolonged withdrawal. Furthermore, they suggest that activation of mGluR1 may represent a potential strategy for reducing cue-induced cocaine craving in abstinent cocaine addicts.
Keywords
  • Benzoxazines,
  • Biophysics,
  • Calcium,
  • Calcium Channel Blockers,
  • Cocaine,
  • Dopamine Uptake Inhibitors,
  • Drug Dose-Response Relationship,
  • Enzyme Inhibitors,
  • Excitatory Amino Acid Antagonists,
  • Excitatory Postsynaptic Potentials,
  • Methoxyhydroxyphenylglycol,
  • Morpholines,
  • Naphthalenes,
  • Neurons,
  • Pharmacology,
  • Drug Effects,
  • Nucleus Accumbens,
  • Piperidines,
  • Protein Kinase C,
  • Pyrazoles,
  • AMPA Receptors,
  • Synapses
Publication Date
October 12, 2011
DOI
10.1523/JNEUROSCI.3625-11.2011
Citation Information
James E. McCutcheon, Jessica A. Loweth, Kerstin A. Ford, Michela Marinelli, et al.. "Group I mGluR Activation Reverses Cocaine-Induced Accumulation of Calcium-Permeable AMPA Receptors in Nucleus Accumbens Synapses via a Protein Kinase C-Dependent Mechanism" The Journal of Neuroscience Vol. 31 Iss. 41 (2011) p. 14536 - 14541 ISSN: Print: 0270-6474 Online: 1529-2401
Available at: http://works.bepress.com/jessica-loweth/14/
Creative Commons license
Creative Commons License
This work is licensed under a Creative Commons CC_BY International License.