Segregation of Amphetamine Reward and Locomotor Stimulation between Nucleus Accumbens Medial Shell and Core

Abstract

Convergent evidence suggests that amphetamine (AMPH) exerts its rewarding and locomotor stimulating effects via release of dopamine in the nucleus accumbens. However, there is no consensus as to the relative contributions of core and medial shell subregions to these effects. Moreover, the literature is based primarily on intracranial administration, which cannot fully mimic the drug distribution achieved by systemic administration. In the present study, the effects of bilateral 6-hydroxydopamine lesions of the accumbens core or medial shell on rewarding and locomotor stimulating effects of systemically administered amphetamine (0.75 mg/kg, i.p.) were examined in a conditioned place preference (CPP) procedure relying solely on tactile cues (floor texture). Residual dopamine innervation was quantified by [125I]-RTI-55 binding to the dopamine transporter. When lesions were performed before the conditioning phase, AMPH-induced locomotor stimulation and CPP magnitude were positively correlated with residual dopamine transporter binding in core and medial shell, respectively. Medial shell lesions did not affect morphine CPP, arguing that a sensory or mnemonic deficit was not responsible for the lesion-induced reduction in AMPH CPP. Medial shell lesions performed between the conditioning phase and the test day reduced the expression of amphetamine CPP. These results suggest that after systemic amphetamine administration, rewarding and locomotor stimulating effects of the drug are anatomically dissociated within the nucleus accumbens: the medial shell contributes to rewarding effects, whereas the core contributes to behavioral activation.

The Effects of Temporary Inactivation of the Core and the Shell Subregions of the Nucleus Accumbens on Prepulse Inhibition of the Acoustic Startle Reflex and Activity in Rats

“…Similar findings were reported by Johnson et al (1996) and Parkinson et al (1999). Furthermore, the core subregion appears to be the site of action for psychostimulant (such as amphetamine or nicotine)-induced locomotor activity (Boye et al, 2001;Parkinson et al, 1999;Sellings and Clarke, 2003; but see Weiner et al, 1996). Yet, our own recent findings as well as data of others indicate that the apparently less significant role of the shell subregion in locomotor activity remains ambiguous.…”

“…At the same time, other neurotransmitter systems within the nucleus accumbens, such as the dopaminergic system, can exert concomitant effects on the altered accumbal GABAergic system. Notably, damage to this neurotransmitter system as well as stimulation via dopaminergic agonists infused into the accumbens has been shown to result in enhanced locomotor activity (eg Boye et al, 2001;Jones et al, 1981;Parkinson et al, 1999;Sellings and Clarke, 2003; but see Taghzouti et al, 1985).…”

Reduced Dopamine Terminal Function and Insensitivity to Cocaine Following Cocaine Binge Self-Administration and Deprivation

“…One idea is that the shell mediates the rewarding effects of drugs of abuse while the core mediates the locomotor stimulant effects (Carlezon and Wise, 1996;Ikemoto et al, 1997;Boye et al, 2001;Sellings and Clarke, 2003). Cocaine and amphetamine appear to preferentially increase glucose utilization in the shell compared with the core of the Nac, and morphine, nicotine, cocaine, and amphetamine preferentially increased extracellular DA in the shell over the core (Pontieri et al, 1995(Pontieri et al, , 1996.…”

Individual Differences in Cocaine- and Amphetamine-Induced Activation of Male Sprague–Dawley Rats: Contribution of the Dopamine Transporter

“…However, NAc studies will be challenging. Recent studies suggest locomotor activation is associated with the shell, but not the core (Sellings and Clarke, 2003). Currently, we can measure [ 3 H]DA uptake only in synaptosomes prepared from the entire NAc because of its small size.…”