The nucleus accumbens shell in reinstatement and extinction of drug seeking

Abstract

The contexts where drugs are self-administered have important control over relapse and extinction of drug-seeking behavior. The nucleus accumbens shell (AcbSh) is essential to this contextual control over drug-seeking behavior. It has been consistently implicated in both the expression of context-induced reinstatement and the expression of extinction, across a variety of drug classes and other rewards. Here, we review the evidence linking AcbSh to the extinction and reinstatement of drug seeking. We consider whether this dual role can be linked to known heterogeneities in AcbSh cell types, their major afferents, and their major efferents. We show that although these heterogeneities are each important and can determine extinction vs. reinstatement, they do not seem adequate to explain the body of findings from the behavioral literature. Rather, we suggest that this functional specialization of AcbSh may be more profitably viewed in terms of the segregation and compartmentalization of AcbSh channels.

Dissociable roles of the nucleus accumbens core and shell subregions in the expression and extinction of conditioned fear

“…There may be some overlap in appetitive and aversive circuits within the NAc. For instance, the NAc core is involved in the self-administration of rewarding stimuli ( LaLumiere and Kalivas, 2008 ; Bull et al, 2014 ), but the NAc shell is reported to be involved in the context-dependent control of both reinstatement and extinction of drug seeking ( Peters et al, 2009 ; Millan et al, 2010 ; Gibson et al, 2019 ). Thus, the regional associations have some overlap for expression and extinction of appetitive and aversive responses but are not strictly segregated.…”

Extinction and drug‐induced reinstatement of cocaine seeking following self‐administration or conditioned place preference in adolescent and adult rats

“…PFC function is necessary for context and cue extinction (Laurent & Westbrook, 2009), and there is evidence in humans and rodents that resistance to cue extinction is associated with reduced PFC plasticity in adolescence (Ganella, Drummond, Ganella, Whittle, & Kim, 2018; Kim, Li, & Richardson, 2011). While the PFC is also involved in instrumental extinction (Gass & Chandler, 2013; Peters, Kalivas, & Quirk, 2009), other brain regions such as NAc play a more critical role (Gibson, Millan, & McNally, 2019; Millan, Marchant, & McNally, 2011). There is evidence that the NAc matures faster than the PFC in rodents and humans (Mengler et al., 2014; Mills, Goddings, Clasen, Giedd, & Blakemore, 2014), explaining why context extinction but not instrumental extinction was impaired in adolescent rats.…”

Blockade of D3 receptor prevents changes in DAT and D3R expression in the mesolimbic dopaminergic circuit produced by social stress- and cocaine prime-induced reinstatement of cocaine-CPP

“…Furthermore, stressful life events can promote relapse in addicts’ drug-seeking drive by impinging upon the mesolimbic DA system, although the underlying mechanisms are poorly understood (Cabib and Puglisi-Allegra, 2012; McCutcheon et al, 2012). Early studies have shown that stressors strongly activate the dopaminergic projection from ventral tegmental area (VTA) to NAc, and that the subregion NAc shell is especially important for contextual control over relapse (Gibson et al, 2019).…”