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Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: interaction of GABA(B) and D2 receptors.
Neuroscience 2012; 226:29-39N

Abstract

Neurons of the ventral tegmental area (VTA) are critical in the rewarding and reinforcing properties of drugs of abuse. Desensitization of VTA neurons to moderate extracellular concentrations of dopamine (DA) is dependent on protein kinase C (PKC) and intracellular calcium levels. This desensitization is called DA inhibition reversal, as it requires concurrent activation of D2 and D1-like receptors; activation of D2 receptors alone does not result in desensitization. Activation of other G-protein-linked receptors can substitute for D1 activation. Like D2 receptors, GABA(B) receptors in the VTA are coupled to G-protein-linked potassium channels. In the present study, we examined interactions between a GABA(B) agonist, baclofen, and dopamine agonists, dopamine and quinpirole, to determine whether there was some interaction in the processes of desensitization of GABA(B) and D2 responses. Long-duration administration of baclofen alone produced reversal of the baclofen-induced inhibition indicative of desensitization, and this desensitization persisted for at least 60 min after baclofen washout. Desensitization to baclofen was dependent on PKC. Dopamine inhibition was reduced for 30 min after baclofen-induced desensitization and conversely, the magnitude of baclofen inhibition was reduced for 30 min by long-duration application of dopamine, but not quinpirole. These results indicate that D2 and GABA(B) receptors share some PKC-dependent mechanisms of receptor desensitization.

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.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

22986166

Citation

Nimitvilai, S, et al. "Reversal of Inhibition of Putative Dopaminergic Neurons of the Ventral Tegmental Area: Interaction of GABA(B) and D2 Receptors." Neuroscience, vol. 226, 2012, pp. 29-39.
Nimitvilai S, Arora DS, McElvain MA, et al. Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: interaction of GABA(B) and D2 receptors. Neuroscience. 2012;226:29-39.
Nimitvilai, S., Arora, D. S., McElvain, M. A., & Brodie, M. S. (2012). Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: interaction of GABA(B) and D2 receptors. Neuroscience, 226, pp. 29-39. doi:10.1016/j.neuroscience.2012.08.045.
Nimitvilai S, et al. Reversal of Inhibition of Putative Dopaminergic Neurons of the Ventral Tegmental Area: Interaction of GABA(B) and D2 Receptors. Neuroscience. 2012 Dec 13;226:29-39. PubMed PMID: 22986166.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of inhibition of putative dopaminergic neurons of the ventral tegmental area: interaction of GABA(B) and D2 receptors. AU - Nimitvilai,S, AU - Arora,D S, AU - McElvain,M A, AU - Brodie,M S, Y1 - 2012/09/15/ PY - 2012/06/15/received PY - 2012/08/21/revised PY - 2012/08/23/accepted PY - 2012/9/19/entrez PY - 2012/9/19/pubmed PY - 2013/4/23/medline SP - 29 EP - 39 JF - Neuroscience JO - Neuroscience VL - 226 N2 - Neurons of the ventral tegmental area (VTA) are critical in the rewarding and reinforcing properties of drugs of abuse. Desensitization of VTA neurons to moderate extracellular concentrations of dopamine (DA) is dependent on protein kinase C (PKC) and intracellular calcium levels. This desensitization is called DA inhibition reversal, as it requires concurrent activation of D2 and D1-like receptors; activation of D2 receptors alone does not result in desensitization. Activation of other G-protein-linked receptors can substitute for D1 activation. Like D2 receptors, GABA(B) receptors in the VTA are coupled to G-protein-linked potassium channels. In the present study, we examined interactions between a GABA(B) agonist, baclofen, and dopamine agonists, dopamine and quinpirole, to determine whether there was some interaction in the processes of desensitization of GABA(B) and D2 responses. Long-duration administration of baclofen alone produced reversal of the baclofen-induced inhibition indicative of desensitization, and this desensitization persisted for at least 60 min after baclofen washout. Desensitization to baclofen was dependent on PKC. Dopamine inhibition was reduced for 30 min after baclofen-induced desensitization and conversely, the magnitude of baclofen inhibition was reduced for 30 min by long-duration application of dopamine, but not quinpirole. These results indicate that D2 and GABA(B) receptors share some PKC-dependent mechanisms of receptor desensitization. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/22986166/Reversal_of_inhibition_of_putative_dopaminergic_neurons_of_the_ventral_tegmental_area:_interaction_of_GABA_B__and_D2_receptors_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(12)00879-2 DB - PRIME DP - Unbound Medicine ER -