Self-infusion of GABA(A) antagonists directly into the ventral tegmental area and adjacent regions

This study used an intracerebral self-administration paradigm in rats to determine if blockade of GABA(A) receptors in the ventral tegmental area (VTA) has a reinforcing effect. Rats quickly learned to self-infuse a picrotoxin solution into the anterior VTA; rats discriminated the lever that produced picrotoxin infusions from the lever without consequences; and when the response requirement was increased, rats increased response levels for picrotoxin infusion. The reinforcing effect of picrotoxin was site-specific: Anterior VTA regions supported vigorous self-infusion, but not the posterior VTA, substantia nigra, or lateral hypothalamus. Muscimol, a GABA(A) agonist, disrupted picrotoxin self-infusion, but bicuculline, a GABA(A) antagonist, was self-infused into the VTA. The results suggest that blockade of GABA(A) receptors in the anterior VTA is reinforcing and that functional organization of the GABA systems within the VTA is heterogeneous.