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Fondation pour la Recherche Medicale<br />

Fédération pour la recherche sur le cerveau<br />

ENINET (LHSM-CT-2005-019063)<br />

Title: The GABAergic tail of <strong>the</strong> ventral tegmental area: A new control center <strong>for</strong> <strong>the</strong><br />

dopaminergic system<br />

Authors: J. KAUFLING, P. VEINANTE, S. PAWLOWSKI, *R. SCHLICHTER, M.-J.<br />

FREUND-MERCIER, M. BARROT;<br />

CNRS UPR 3212, Univ. Strasbourg, Strasbourg 67084, Fr<strong>an</strong>ce<br />

Abstract: The tr<strong>an</strong>scription factor ∆FosB is implicated in <strong>the</strong> plasticity induced by drugs of<br />

abuse. We showed that psychostimul<strong>an</strong>ts induce ∆FosB in GABA cells of a caudal subregion of<br />

<strong>the</strong> ventral tegmental area (VTA) which was named tail of <strong>the</strong> VTA (tVTA). While tVTA mostly<br />

shares VTA inputs, its outputs remained to be characterized. tVTA efferents were studied by<br />

iontophoretic injections of <strong>the</strong> <strong>an</strong>terograde tracer biotinylated dextr<strong>an</strong> amine (BDA). To fur<strong>the</strong>r<br />

study VTA inputs arising <strong>from</strong> tVTA, injections of <strong>the</strong> retrograde tracer Fluoro-Gold® were<br />

combined with multiple labeling by immunohistochemistry in rats treated with cocaine. The<br />

indirect projection <strong>from</strong> <strong>the</strong> tVTA to <strong>the</strong> nucleus accumbens was assessed by using a doubletracing<br />

approach, with cholera toxin B subunit (CTB) delivered in <strong>the</strong> nucleus accumbens <strong>an</strong>d<br />

BDA in <strong>the</strong> tVTA. Tract-tracing studies showed that tVTA heavily projects to <strong>the</strong> midbrain<br />

dopaminergic system <strong>an</strong>d revealed terminal appositions with dopamine cells in <strong>the</strong> VTA.<br />

Double-labeling studies demonstrated that this tVTA output is mostly GABAergic, that it<br />

includes cells in which cocaine exposure induces ∆FosB, <strong>an</strong>d that it contacts dopamine cells<br />

projecting to <strong>the</strong> nucleus accumbens. GABA neurons expressing ∆FosB in <strong>the</strong> tVTA after<br />

cocaine exposure thus project to <strong>the</strong> dopamine mesolimbic neurons.<br />

This work was supported by <strong>the</strong> Centre national de la Recherche Scientifique (contracts<br />

UMR7168 <strong>an</strong>d UPR3212), <strong>the</strong> University of Strasbourg (contract UMR7168), <strong>the</strong> Fondation<br />

pour la Recherche Médicale (M.B.), <strong>the</strong> Fédération pour la Recherche sur le Cerveau (P.V.) <strong>an</strong>d<br />

<strong>the</strong> ENINET (Europe<strong>an</strong> Commission contract LHSM-CT-2005-019063).<br />

Disclosures: J. Kaufling, None; P. Vein<strong>an</strong>te, None; S. Pawlowski, None; R. Schlichter ,<br />

None; M. Freund-Mercier, None; M. Barrot, None.<br />

Poster<br />

550. Neural Plasticity, Dependence, <strong>an</strong>d Addiction<br />

Location: South Hall A<br />

Time: Tuesday, October 20, <strong>2009</strong>, 8:00 am - 12:00 noon

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