gamma-Aminobutyric acid cells with cocaine-induced DeltaFosB in the ventral tegmental area innervate mesolimbic neurons.
BACKGROUND
The transcription factor DeltaFosB is implicated in the plasticity induced by drugs of abuse. We showed that psychostimulants induce DeltaFosB in gamma-aminobutyric acid (GABA) cells of a caudal subregion of the ventral tegmental area (VTA) that was named tail of the VTA (tVTA). Although tVTA mostly shares VTA inputs, its outputs remain to be characterized.


METHODS
The tVTA efferents were studied by iontophoretic injections of the anterograde tracer biotinylated dextran amine (BDA). To further study VTA inputs arising from tVTA, injections of the retrograde tracer Fluoro-Gold were combined with multiple labeling by immunohistochemistry in rats treated with cocaine. Indirect projections from the tVTA to the nucleus accumbens were assessed with a double-tracing approach, cholera toxin B subunit (CTB) being delivered in the nucleus accumbens and BDA in the tVTA.


RESULTS
Tract-tracing studies showed that tVTA heavily projects to the midbrain dopaminergic system and revealed terminal appositions with dopamine cells in the VTA. Double-labeling studies demonstrated that this tVTA output is mostly GABAergic, includes cells in which cocaine exposure induces DeltaFosB, and displays appositions to dopamine cells projecting to the nucleus accumbens.


CONCLUSIONS
The GABA neurons expressing DeltaFosB in the tVTA after cocaine exposure project to the dopamine mesolimbic neurons.
Kaufling
Jennifer
J
Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, Strasbourg, France.
Veinante
Pierre
P
Pawlowski
Sophie A
SA
Freund-Mercier
Marie-José
MJ
Barrot
Michel
M
D000818:Animals; D001710:Biotin / Q000031:analogs & derivatives / Q000378:metabolism; D002772:Cholera Toxin / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003911:Dextrans / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D008032:Limbic System / Q000166:cytology; D008297:Male; D009434:Neural Pathways / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013266:Stilbamidines / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D003911:Dextrans; D018765:Dopamine Uptake Inhibitors; D016760:Proto-Oncogene Proteins c-fos; D013266:Stilbamidines; C076397:biotinylated dextran amine; D005680:gamma-Aminobutyric Acid; D001710:Biotin; D002772:Cholera Toxin; D014446:Tyrosine 3-Monooxygenase; D003042:Cocaine