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Addiction and synaptic plasticity: Cocaine-induced redistribution of glutamate receptors in the ventral tegmental area

English title Addiction and synaptic plasticity: Cocaine-induced redistribution of glutamate receptors in the ventral tegmental area
Applicant Lüscher Christian
Number 109871
Funding scheme Project funding (Div. I-III)
Research institution Dépt des Neurosciences Fondamentales Faculté de Médecine Université de Genève
Institution of higher education University of Geneva - GE
Main discipline Neurophysiology and Brain Research
Start/End 01.10.2005 - 30.09.2010
Approved amount 837'000.00
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Keywords (7)

addiction; synaptic plasticity; NEUROBIOLOGY; REWARD; VENTRAL TEGMENTAL AREA; GLUTAMATE RECEPTORS; COCAINE

Lay Summary (English)

Lead
Lay summary
Addictive drugs have in common that they induce synaptic plasticity of glutamate transmission in the VTA. Already after a single exposure, synapses are strengthened, in part by driving the synaptic insertion of glutamate receptors of the AMPA type that lack the subunit GluR2. AMPA-transmission becomes calcium permeable for several days. We have observed that the activation of metabotropic glutamate receptors (mGluR1) restores basal calcium-impermeable transmission within minutes (Bellone & Lüscher, Nature Neurosci., 2006). Moreover, we provide evidence that the synapse expresses LTD, not because there are fewer receptors, but because the conductance of newly inserted GluR2-containing AMPARs is smaller than that of GluR2-lacking AMPARs that were present prior to LTD. In addition, we find that de novo synthesis of GluR2 is required within minutes of LTD induction. (Mameli et al., Science, 2007). We will now test the molecular underpinnings of the Cocaine-induced plasticity and will attempt to unravel the behavioral implications of mGluR-LTD in the VTA. Since a large body of literature suggests that synaptic plasticity in the VTA underlies core components of drug-induced behavioral changes in animals, activation of mGluR1s may emerge as a novel strategy for treatment of addiction.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
132729 Spiraling towards relapse: a network approach to addiction 01.10.2010 Project funding (Div. I-III)

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