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

ABSTRACT

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.