gamma-Aminobutyric Acid Cells with Cocaine-Induced Delta FosB in the Ventral Tegmental Area Innervate Mesolimbic Neurons

Background: The transcription factor Delta FosB is implicated in the plasticity induced by drugs of abuse. We showed that psychostimulants induce Delta FosB 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 Delta FosB, and displays appositions to dopamine cells projecting to the nucleus accumbens. Conclusions: The GABA neurons expressing Delta FosB in the tVTA after cocaine exposure project to the dopamine mesolimbic neurons.