gamma-Aminobutyric acid cells with cocaine-induced DeltaFosB in the ventral tegmental area innervate mesolimbic neurons

Biol Psychiatry. 2010 Jan 1;67(1):88-92. doi: 10.1016/j.biopsych.2009.08.001.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biotin / analogs & derivatives
  • Biotin / metabolism
  • Cholera Toxin / metabolism
  • Cocaine / pharmacology*
  • Dextrans / metabolism
  • Dopamine Uptake Inhibitors / pharmacology*
  • Limbic System / cytology
  • Male
  • Neural Pathways / metabolism
  • Neurons / drug effects
  • Neurons / physiology*
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stilbamidines / metabolism
  • Tyrosine 3-Monooxygenase / metabolism
  • Ventral Tegmental Area / drug effects*
  • gamma-Aminobutyric Acid / metabolism*


  • 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
  • Dextrans
  • Dopamine Uptake Inhibitors
  • Proto-Oncogene Proteins c-fos
  • Stilbamidines
  • biotinylated dextran amine
  • gamma-Aminobutyric Acid
  • Biotin
  • Cholera Toxin
  • Tyrosine 3-Monooxygenase
  • Cocaine