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Reversal of quinpirole inhibition of ventral tegmental area neurons is linked to the phosphatidylinositol system and is induced by agonists linked to G(q).
J Neurophysiol 2012; 108(1):263-74JN

Abstract

Putative dopaminergic (pDAergic) ventral tegmental area neurons play an important role in brain pathways related to addiction. Extended exposure of pDAergic neurons to moderate concentrations of dopamine (DA) results in a time-dependent decrease in sensitivity of pDAergic neurons to DA inhibition, a process called dopamine inhibition reversal (DIR). We have shown that DIR is mediated by phospholipase C and conventional protein kinase C through concurrent stimulation of D2 and D1-like receptors. In the present study, we further characterized this phenomenon by using extracellular recordings in brain slices to examine whether DIR is linked to phosphatidylinositol (PI) or adenylate cyclase (AC) second-messenger pathways. A D1-like dopaminergic agonist associated with PI turnover (SKF83959), but not one linked to AC (SKF83822), promoted reversal of inhibition produced by quinpirole, a dopamine D2-selective agonist. Other neurotransmitter receptors linked to PI turnover include serotonin 5-HT(2), α(1)-adrenergic, neurotensin, and group I metabotropic glutamate (mGlu) receptors. Both serotonin and neurotensin produced significant reversal of quinpirole inhibition, but agonists of α(1)-adrenergic and group I mGlu receptors failed to significantly reverse quinpirole inhibition. These results indicate that some agonists that stimulate PI turnover can facilitate desensitization of D2 receptors but that there may be other factors in addition to PI that control that interaction.

Authors+Show Affiliations

Department of Physiology and Biophysics, University of Illinois at Chicago, 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

22490559

Citation

Nimitvilai, Sudarat, et al. "Reversal of Quinpirole Inhibition of Ventral Tegmental Area Neurons Is Linked to the Phosphatidylinositol System and Is Induced By Agonists Linked to G(q)." Journal of Neurophysiology, vol. 108, no. 1, 2012, pp. 263-74.
Nimitvilai S, McElvain MA, Arora DS, et al. Reversal of quinpirole inhibition of ventral tegmental area neurons is linked to the phosphatidylinositol system and is induced by agonists linked to G(q). J Neurophysiol. 2012;108(1):263-74.
Nimitvilai, S., McElvain, M. A., Arora, D. S., & Brodie, M. S. (2012). Reversal of quinpirole inhibition of ventral tegmental area neurons is linked to the phosphatidylinositol system and is induced by agonists linked to G(q). Journal of Neurophysiology, 108(1), pp. 263-74. doi:10.1152/jn.01137.2011.
Nimitvilai S, et al. Reversal of Quinpirole Inhibition of Ventral Tegmental Area Neurons Is Linked to the Phosphatidylinositol System and Is Induced By Agonists Linked to G(q). J Neurophysiol. 2012;108(1):263-74. PubMed PMID: 22490559.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reversal of quinpirole inhibition of ventral tegmental area neurons is linked to the phosphatidylinositol system and is induced by agonists linked to G(q). AU - Nimitvilai,Sudarat, AU - McElvain,Maureen A, AU - Arora,Devinder S, AU - Brodie,Mark S, Y1 - 2012/04/04/ PY - 2012/4/12/entrez PY - 2012/4/12/pubmed PY - 2012/12/10/medline SP - 263 EP - 74 JF - Journal of neurophysiology JO - J. Neurophysiol. VL - 108 IS - 1 N2 - Putative dopaminergic (pDAergic) ventral tegmental area neurons play an important role in brain pathways related to addiction. Extended exposure of pDAergic neurons to moderate concentrations of dopamine (DA) results in a time-dependent decrease in sensitivity of pDAergic neurons to DA inhibition, a process called dopamine inhibition reversal (DIR). We have shown that DIR is mediated by phospholipase C and conventional protein kinase C through concurrent stimulation of D2 and D1-like receptors. In the present study, we further characterized this phenomenon by using extracellular recordings in brain slices to examine whether DIR is linked to phosphatidylinositol (PI) or adenylate cyclase (AC) second-messenger pathways. A D1-like dopaminergic agonist associated with PI turnover (SKF83959), but not one linked to AC (SKF83822), promoted reversal of inhibition produced by quinpirole, a dopamine D2-selective agonist. Other neurotransmitter receptors linked to PI turnover include serotonin 5-HT(2), α(1)-adrenergic, neurotensin, and group I metabotropic glutamate (mGlu) receptors. Both serotonin and neurotensin produced significant reversal of quinpirole inhibition, but agonists of α(1)-adrenergic and group I mGlu receptors failed to significantly reverse quinpirole inhibition. These results indicate that some agonists that stimulate PI turnover can facilitate desensitization of D2 receptors but that there may be other factors in addition to PI that control that interaction. SN - 1522-1598 UR - https://www.unboundmedicine.com/medline/citation/22490559/Reversal_of_quinpirole_inhibition_of_ventral_tegmental_area_neurons_is_linked_to_the_phosphatidylinositol_system_and_is_induced_by_agonists_linked_to_G_q__ L2 - http://www.physiology.org/doi/full/10.1152/jn.01137.2011?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -