Abstract

Rats learn to lever-press for phencyclidine (PCP; NMDA channel blocker and dopamine uptake inhibitor), MK-801 (NMDA channel blocker), and nomifensine (dopamine uptake inhibitor) infusions directly into the shell but not the core subterritory of the nucleus accumbens septi (NAS). PCP, MK-801 and nomifensine are thought, through different means, to inhibit a final common path: NAS intrinsic GABAergic output neurons projecting to the ventral tegmental area (VTA). Independent groups of animals were tested to determine whether infusions of PCP, MK-801, or nomifensine directly into the core or shell subterritory of the NAS would induce Fos expression within the VTA. Each rat received a total of 26 unilateral infusions (over a 60 min period) of PCP, MK-801, nomifensine (12 nmol, 1.2 nmol, or 1.7 nmol respectively, per 120 nl infusion) or vehicle into either the NAS core or shell; each animal's infusions were "yoked" to the rate and pattern of administration of a rat that had previously learned to lever-press for PCP infusions. The rats were sacrificed and their brains were processed for histological analysis of Fos-immunoreactivity 75 min after the first infusion of drug. Each drug induced significantly more Fos-positive cells within the lateral and medial VTA. MK-801 and PCP infused into the NAS shell, each induced more Fos within the medial VTA. Overall, Fos induction within the VTA was differentially expressed within the rostral to caudal levels of the VTA. In sum, the present thesis provides preliminary evidence linking suppression of intrinsic NAS GABAergic neurons, via both NMDA receptor and dopamine reuptake blockade, to the activation of neurons within the VTA.