Amphetamine-induced neurochemical and locomotor responses are expressed differentially across the anteroposterior axis of the core and shell subterritories of the nucleus accumbens.

Abstract

The administration of psychostimulants increases dopamine (DA) release within the nucleus accumbens (NAC), a terminal projection site of mesolimbic DA neurons, originating in the ventral tegmental area (VTA). Recent evidence demonstrates that two subdivisions of the NAC, the dorsolateral core and the ventromedial shell, can be distinguished by morphological and immunohistochemical differences, as well as by their distinct anatomical connections. It has been suggested that these two subregions subserve different functions that are related to goal-directed behaviors, stimulus-reward associations, and reinforcement induced by addictive drugs. The shell region, in particular, modulates inputs from the limbic system, whereas the core is preferentially innervated by nuclei that process motor information. In the present study, we sought to investigate if (1) the direct infusion of d-amphetamine (AMPH) by reverse microdialysis into either the core or shell of the NAC across its anteroposterior axis differentially affects dialysate DA and 5-HT levels, and (2) these subterritories also subserve different behavioral functions. Following the determination of basal DA and 5-HT levels, four increasing concentrations of AMPH (0.05, 0.10, 0.50, 1.00 microM) were substituted for the dialysis perfusate for 60 min each. Movement units were detected by an infrared sensor and were transmitted through a motion interface to an activity monitor analyzer. AMPH produced a dose-dependent increase in locomotor activity after microinfusion into either the rostral shell, caudal shell or core of the NAC. The potency of the AMPH-induced locomotor activating effect was significantly higher in the rostral shell of the NAC compared with the caudal shell and the core. The lowest concentrations of AMPH (0.05, 0.1 microM) produced an equipotent decrease in dialysate DA in either the rostral shell, caudal shell, or core. At 1.0 microM, however, AMPH selectively increased DA in the rostral shell, whereas DA reached baseline values both in the caudal shell and core. Basal dialysate DA levels were significantly higher in the core relative to both the rostral and caudal parts of the shell. The highest dose of AMPH significantly increased dialysate 5-HT levels over baseline only in the caudal shell of the NAC. The basal dialysate 5-HT levels did not significantly differ between the three subterritories of the NAC. These results emphasize the heterogeneity and functional compartmentalization within the NAC, the differential regulation of neurochemical and motor responses across the anteroposterior axis of the NAC, and the preferential effect of AMPH in the rostral shell subterritory of the NAC.