Cooperative and dissociable involvement of the nucleus accumbens core and shell in the promotion and inhibition of actions during active and inhibitory avoidance

The flexible implementation of active and passive strategies to avoid danger is critical to survival. Conversely, the inappropriate allocation of these behaviors may underlie pathological avoidance in neuropsychiatric illnesses. The present study investigated whether these two poles of avoidance may be differentially regulated by subdivsions of the nucleus accumbens, the core (NAcC) and shell (NAcS), which are known to bi-directionally control flexible action selection during reward-seeking. In so doing, we developed a novel cued active/inhibitory avoidance task conducted in operant chambers that entailed presentations of two distinct, 15 s auditory cues. One cue indicated that impending foot-shocks could be avoided by pressing a lever (active avoidance), whereas another cue signaled that shocks could be avoided by withholding presses (inhibitory avoidance). In well-trained rats, pharmacological inactivation of either the NAcC or NAcS impaired active avoidance. In contrast, inhibitory avoidance was disrupted by inactivation of the NAcS, but not NAcC, reflecting a deficit in response-inhibition that manifested as more inhibitory avoidance failures and lever-presses, as well as increased locomotion. Foot-shock sensitivity was unaffected by inactivation of either subregion. In a subsequent experiment, treatment with the monoamine releaser a-amphetamine (1 mg/kg) did not affect active avoidance, but disinhibited lever pressing during inhibitory avoidance trials. These results provide novel insight into the ventral striatal and monoaminergic regulation of flexible response allocation and inhibition that facilitates avoidance behavior and highlight the importance of different subregions of the NAc in action selection during aversively-motivated behaviors. (C) 2018 Elsevier Ltd. All rights reserved.