Amphetamine microinfusion in the dorso-ventral axis of the prefrontal cortex differentially modulates dopamine neurotransmission in the shell-core subterritories of the nucleus accumbens.

Abstract

The two main subdivisions of the nucleus accumbens (NAC), the dorsolateral core and the ventromedial shell, can be distinguished by a distinct connectivity pattern originating mainly from the prefrontal cortex (PFC).1,2 More specifically, the core of the NAC receives major projections from the anterior cingulate and dorsocaudal prelimbic cortices, which are referred to as the dorsal PFC.3,4 In contrast to the core, the shell of the NAC receives main afferents from the ventral prelimbic and rostral infralimbic cortices, which are termed the ventral PFC.3,4 The present study sought to evaluate the contributions of the ventral prelimbic/infralimbic cortices and shell subterritory of the NAC as well as the dorsal prelimbic/anterior cingulate cortices and core subregion of the NAC to the microinfusion of amphetamine (AMPHE) on dialysate DA levels using a dual-probe microdialysis design. Male Wistar rats were anesthetized with sodium pentobarbital (60 mg/kg, i.p.) and mounted on a stereotaxic apparatus. The skull was exposed and two holes were drilled for unilateral placement of microdialysis probes into (1) the core of the NAC and the dorsal PFC, and (2) the shell of the NAC and the ventral PFC. One-hourly dose of chloral hydrate (100 mg/kg, i.p.) was administered to maintain a constant level of anesthesia throughout the experiment. Following the determination of basal DA levels, 5 increasing concentrations of AMPHE (1, 10, 100, 500, 1000 μM) were substituted for the dialysis perfusate in the PFC for 60 min each. Both microdialysis procedures and chromatographic analyses of brain microdialysates were the same as described previously.5 Basal DA levels were significantly higher in the ventral PFC compared with the dorsal PFC and higher concentrations of DA were also observed in the core of the NAC compared with its shell counterpart (FIG. 1A). Reverse microdialysis of AMPHE in the ventral PFC produced a significant dose-dependent decrease in dialysate DA levels. In contrast, no significant alterations in DA levels were observed following AMPHE microinfusion in the dorsal PFC (FIG. 2A). Furthermore, the