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Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA

Padgett, Claire L. and Lalive, Arnaud L. and Tan, Kelly R. and Terunuma, Miho and Munoz, Michaelanne B. and Pangalos, Menelas N. and Martínez-Hernández, José and Watanabe, Masahiko and Moss, Stephen J. and Luján, Rafael and Lüscher, Christian and Slesinger, Paul A.. (2012) Methamphetamine-evoked depression of GABA(B) receptor signaling in GABA neurons of the VTA. Neuron, 73 (5). pp. 978-989.

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Official URL: http://edoc.unibas.ch/50648/

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Abstract

Psychostimulants induce neuroadaptations in excitatory and fast inhibitory transmission in the ventral tegmental area (VTA). Mechanisms underlying drug-evoked synaptic plasticity of slow inhibitory transmission mediated by GABA(B) receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir(3)) channels, however, are poorly understood. Here, we show that 1 day after methamphetamine (METH) or cocaine exposure both synaptically evoked and baclofen-activated GABA(B)R-GIRK currents were significantly depressed in VTA GABA neurons and remained depressed for 7 days. Presynaptic inhibition mediated by GABA(B)Rs on GABA terminals was also weakened. Quantitative immunoelectron microscopy revealed internalization of GABA(B1) and GIRK2, which occurred coincident with dephosphorylation of serine 783 (S783) in GABA(B2), a site implicated in regulating GABA(B)R surface expression. Inhibition of protein phosphatases recovered GABA(B)R-GIRK currents in VTA GABA neurons of METH-injected mice. This psychostimulant-evoked impairment in GABA(B)R signaling removes an intrinsic brake on GABA neuron spiking, which may augment GABA transmission in the mesocorticolimbic system.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Neurobiology > Physiopathology of basal ganglia neuronal subcircuits (Tan)
UniBasel Contributors:Tan, Kelly
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Elsevier
ISSN:0896-6273
e-ISSN:1097-4199
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:30 Nov 2017 11:26
Deposited On:30 Nov 2017 11:26

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