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Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
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Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
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Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
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Journal Article
Cocaine triggered AMPA receptor redistribution is reversed in vivo by mGluR-dependent long-term depression
2006
Overview
Drugs of abuse induce long-lasting changes in neural circuits that may underlie core components of addiction. Here we focus on glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area (VTA). Using an '
ex vivo
' approach in mice, we show that a single injection of cocaine caused strong rectification and conferred sensitivity to the polyamine Joro spider toxin (JST) of AMPAR-mediated excitatory postsynaptic currents (AMPAR EPSCs), indicating the recruitment of receptors that lack GluR2. This qualitative change in transmission was paralleled by an increase in the AMPAR:NMDAR ratio and was prevented by interfering with the protein interacting with C kinase-1 (PICK1)
in vivo
. Activation of metabotropic glutamate receptors (mGluR1s) by intraperitoneal injection of a positive modulator depotentiated synapses and abolished rectification in slices of cocaine-treated mice, revealing a mechanism to reverse cocaine-induced synaptic plasticity
in vivo
.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animals
/ Araneae
/ Biomedical and Life Sciences
/ Carrier Proteins - pharmacology
/ Cocaine
/ Dopamine Antagonists - pharmacology
/ Dopamine Uptake Inhibitors - pharmacology
/ Dose-Response Relationship, Radiation
/ Electric Stimulation - methods
/ Enzyme Inhibitors - pharmacology
/ Excitatory Postsynaptic Potentials - drug effects
/ Long-Term Synaptic Depression - drug effects
/ Methoxyhydroxyphenylglycol - analogs & derivatives
/ Methoxyhydroxyphenylglycol - pharmacology
/ Mice
/ Nuclear Proteins - pharmacology
/ Patch-Clamp Techniques - methods
/ Receptors, AMPA - metabolism
/ Receptors, Metabotropic Glutamate - metabolism
