Tags

Type your tag names separated by a space and hit enter

Dopamine D2 receptor desensitization by dopamine or corticotropin releasing factor in ventral tegmental area neurons is associated with increased glutamate release.
Neuropharmacology 2014; 82:28-40N

Abstract

Neurons of the ventral tegmental area (VTA) are the source of dopaminergic (DAergic) input to important brain regions related to addiction. Prolonged exposure of these VTA neurons to moderate concentrations of dopamine (DA) causes a time-dependent decrease in DA-induced inhibition, a complex desensitization called DA inhibition reversal (DIR). DIR is mediated by conventional protein kinase C (cPKC) through concurrent stimulation of D2 and D1-like DA receptors, or by D2 stimulation concurrent with activation of some Gq-linked receptors. Corticotropin releasing factor (CRF) acts via Gq, and can modulate glutamater neurotransmission in the VTA. In the present study, we used brain slice electrophysiology to characterize the interaction of DA, glutamate antagonists, and CRF agonists in the induction and maintenance of DIR in the VTA. Glutamate receptor antagonists blocked induction but not maintenance of DIR. Putative blockers of neurotransmitter release and store-operated calcium channels blocked and reversed DIR. CRF and the CRF agonist urocortin reversed inhibition produced by the D2 agonist quinpirole, consistent with our earlier work indicating that Gq activation reverses quinpirole-mediated inhibition. In whole cell recordings, the combination of urocortin and quinpirole, but not either agent alone, increased spontaneous excitatory postsynaptic currents (sEPSCs) in VTA neurons. Likewise, the combination of a D1-like receptor agonist and quinpirole, but not either agent alone, increased sEPSCs in VTA neurons. In summary, desensitization of D2 receptors induced by dopamine or CRF on DAergic VTA neurons is associated with increased glutamatergic signaling in the VTA.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Illinois at Chicago, 835 S. Wolcott, Room E-202, M/C 901, Chicago, IL 60612-7342, USA.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-1150, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Department of Physiology and Biophysics, University of Illinois at Chicago, 835 S. Wolcott, Room E-202, M/C 901, Chicago, IL 60612-7342, USA.Department of Physiology and Biophysics, University of Illinois at Chicago, 835 S. Wolcott, Room E-202, M/C 901, Chicago, IL 60612-7342, USA.Department of Physiology and Biophysics, University of Illinois at Chicago, 835 S. Wolcott, Room E-202, M/C 901, Chicago, IL 60612-7342, USA.Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, SP30-1150, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.Department of Physiology and Biophysics, University of Illinois at Chicago, 835 S. Wolcott, Room E-202, M/C 901, Chicago, IL 60612-7342, USA. Electronic address: mbrodie@uic.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

24657149

Citation

Nimitvilai, Sudarat, et al. "Dopamine D2 Receptor Desensitization By Dopamine or Corticotropin Releasing Factor in Ventral Tegmental Area Neurons Is Associated With Increased Glutamate Release." Neuropharmacology, vol. 82, 2014, pp. 28-40.
Nimitvilai S, Herman M, You C, et al. Dopamine D2 receptor desensitization by dopamine or corticotropin releasing factor in ventral tegmental area neurons is associated with increased glutamate release. Neuropharmacology. 2014;82:28-40.
Nimitvilai, S., Herman, M., You, C., Arora, D. S., McElvain, M. A., Roberto, M., & Brodie, M. S. (2014). Dopamine D2 receptor desensitization by dopamine or corticotropin releasing factor in ventral tegmental area neurons is associated with increased glutamate release. Neuropharmacology, 82, pp. 28-40. doi:10.1016/j.neuropharm.2014.03.006.
Nimitvilai S, et al. Dopamine D2 Receptor Desensitization By Dopamine or Corticotropin Releasing Factor in Ventral Tegmental Area Neurons Is Associated With Increased Glutamate Release. Neuropharmacology. 2014;82:28-40. PubMed PMID: 24657149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine D2 receptor desensitization by dopamine or corticotropin releasing factor in ventral tegmental area neurons is associated with increased glutamate release. AU - Nimitvilai,Sudarat, AU - Herman,Melissa, AU - You,Chang, AU - Arora,Devinder S, AU - McElvain,Maureen A, AU - Roberto,Marisa, AU - Brodie,Mark S, Y1 - 2014/03/19/ PY - 2013/11/08/received PY - 2014/03/06/revised PY - 2014/03/10/accepted PY - 2014/3/25/entrez PY - 2014/3/25/pubmed PY - 2015/1/13/medline KW - Desensitization KW - Dopamine D2 receptor KW - Glutamate KW - Quinpirole KW - Urocortin KW - sEPSC SP - 28 EP - 40 JF - Neuropharmacology JO - Neuropharmacology VL - 82 N2 - Neurons of the ventral tegmental area (VTA) are the source of dopaminergic (DAergic) input to important brain regions related to addiction. Prolonged exposure of these VTA neurons to moderate concentrations of dopamine (DA) causes a time-dependent decrease in DA-induced inhibition, a complex desensitization called DA inhibition reversal (DIR). DIR is mediated by conventional protein kinase C (cPKC) through concurrent stimulation of D2 and D1-like DA receptors, or by D2 stimulation concurrent with activation of some Gq-linked receptors. Corticotropin releasing factor (CRF) acts via Gq, and can modulate glutamater neurotransmission in the VTA. In the present study, we used brain slice electrophysiology to characterize the interaction of DA, glutamate antagonists, and CRF agonists in the induction and maintenance of DIR in the VTA. Glutamate receptor antagonists blocked induction but not maintenance of DIR. Putative blockers of neurotransmitter release and store-operated calcium channels blocked and reversed DIR. CRF and the CRF agonist urocortin reversed inhibition produced by the D2 agonist quinpirole, consistent with our earlier work indicating that Gq activation reverses quinpirole-mediated inhibition. In whole cell recordings, the combination of urocortin and quinpirole, but not either agent alone, increased spontaneous excitatory postsynaptic currents (sEPSCs) in VTA neurons. Likewise, the combination of a D1-like receptor agonist and quinpirole, but not either agent alone, increased sEPSCs in VTA neurons. In summary, desensitization of D2 receptors induced by dopamine or CRF on DAergic VTA neurons is associated with increased glutamatergic signaling in the VTA. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/24657149/Dopamine_D2_receptor_desensitization_by_dopamine_or_corticotropin_releasing_factor_in_ventral_tegmental_area_neurons_is_associated_with_increased_glutamate_release_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(14)00091-4 DB - PRIME DP - Unbound Medicine ER -