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Drug-evoked synaptic plasticity of GABAB receptor signaling in the ventral tegmental area

Defense Thèse de doctorat : Univ. Genève et Lausanne, 2012 - Neur. 85 - 2012/03/14
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 GABAB receptors and G protein-gated inwardly rectifying potassium (GIRK/Kir3) channels, however, are poorly understood. Here, we show that 1 day after methamphetamine (METH) or cocaine exposure both synaptically evoked and baclofen-activated GABABR-GIRK currents were significantly depressed in VTA GABA neurons and remained depressed for 7 days. Presynaptic inhibition mediated by GABABRs on GABA terminals was also weakened. Quantitative immunoelectron microscopy revealed internalization of GABAB1 and GIRK2, which occurred coincident with dephosphorylation of serine 783 (S783) in GABAB2, a site implicated in regulating GABABR surface expression. Inhibition of protein phosphatases recovered GABABR-GIRK currents in VTA GABA neurons of METH-injected mice. This psychostimulant-evoked impairment in GABABR signaling removes an intrinsic brake on GABA neuron spiking, which may augment GABA transmission in the mesocorticolimbic system.
Keywords Synaptic plasticityGABAB receptorMethamphetamineCocaineAddictionBaclofenVentral tegmental areaDopamine
URN: urn:nbn:ch:unige-219889
Note Doctorat en Neurosciences des Universités de Genève et de Lausanne
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LALIVE D'EPINAY, Arnaud. Drug-evoked synaptic plasticity of GABAB receptor signaling in the ventral tegmental area. Université de Genève. Thèse, 2012. doi: 10.13097/archive-ouverte/unige:21988 https://archive-ouverte.unige.ch/unige:21988

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Deposited on : 2012-08-10

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