RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area.

RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Research Abstract Details 

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RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Abstract Text:

,Marta Lomazzi,Hans G Cruz,Cyril Creton,Rafael ,Meng Li,Yuchio Yanagawa,Kunihiko Obata,Masahiko Watanabe,Kevin Wickman,Stephanie B Boyer,Paul A Slesinger,Christian ,Gwenaël Labouèbe,Marta Lomazzi,Hans G Cruz,Cyril Creton,Rafael Luján,Meng Li,Yuchio Yanagawa,Kunihiko Obata,Masahiko Watanabe,Kevin Wickman,Stephanie B Boyer,Paul A Slesinger,Christian Lüscher,

Agonists of GABA(B) receptors exert a bi-directional effect on the activity of dopamine (DA) neurons of the ventral tegmental area, which can be explained by the fact that coupling between GABA(B) receptors and G protein-gated inwardly rectifying potassium (GIRK) channels is significantly weaker in DA neurons than in GABA neurons. Thus, low concentrations of agonists preferentially inhibit GABA neurons and thereby disinhibit DA neurons. This disinhibition might confer reinforcing properties on addictive GABA(B) receptor agonists such as gamma-hydroxybutyrate (GHB) and its derivatives. Here we show that, in DA neurons of mice, the low coupling efficiency reflects the selective expression of heteromeric GIRK2/3 channels and is dynamically modulated by a member of the regulator of G protein signaling (RGS) protein family. Moreover, repetitive exposure to GHB increases the GABA(B) receptor-GIRK channel coupling efficiency through downregulation of RGS2. Finally, oral self-administration of GHB at a concentration that is normally rewarding becomes aversive after chronic exposure. On the basis of these results, we propose a mechanism that might underlie tolerance to GHB.

RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Publishing Authors By Initials

G ,M Lomazzi,HG Cruz,C Creton,R ,M Li,Y Yanagawa,K Obata,M Watanabe,K Wickman,SB Boyer,PA Slesinger,C ,G Labouèbe,M Lomazzi,HG Cruz,C Creton,R Luján,M Li,Y Yanagawa,K Obata,M Watanabe,K Wickman,SB Boyer,PA Slesinger,C Lüscher,

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RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Nature neuroscience

VOLUME: 10

Page Numbers: 1559-68

Journal Abbreviation: Nat. Neurosci.

ISSN: 1097-6256

DAY: 28

MONTH: 10

YEAR: 2007

RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area. Information

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LANGUAGE: eng

NlmUniqueID: 9809671

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Grant and Affiliation Information for RGS2 modulates coupling between GABA(B) receptors and GIRK channels in dopamine neurons of the ventral tegmental area.

AFFILIATION: [1] Department of Basic Neurosciences, Medical Faculty, University of Geneva, 1, Michel- Servet, CH-1211 Geneva, Switzerland. [2] These authors contributed equally to this work.

Country: United States

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MEDLINETA: Nat Neurosci

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