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-infusions, 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.