A role of nucleus accumbens dopamine receptors in the nucleus accumbens core, but not shell, in fear prediction error.

Abstract

Two experiments used an associative blocking design to study the role of dopamine receptors in the nucleus accumbens shell (AcbSh) and core (AcbC) in fear prediction error. Rats in the experimental groups were trained to a visual fear-conditioned stimulus (conditional stimulus [CS]) A in Stage I, whereas rats in the control groups were not. In Stage II, all rats received compound fear conditioning of the visual CSA and an auditory CSB. Rats were later tested for their fear responses to CSB. All rats received microinjections of saline or the D1-D2 receptor antagonist cis-(z)-flupenthixol prior to Stage II. These microinjections targeted either the AcbSh (Experiment 1) or the AcbC (Experiment 2). In each experiment, Stage I fear conditioning of CSA blocked fear learning to CSB. Microinjection of cis-(z)-flupenthixol (10 or 20 μg) into the AcbSh (Experiment 1) had no effect on fear learning or associative blocking. In contrast, microinjection of cis-(z)-flupenthixol (10 or 20 μg) into the AcbC (Experiment 2) attenuated blocking and so enabled fear learning to CSB. These results identify the AcbC as the critical locus for dopamine receptor contributions to fear prediction error and the associative blocking of fear learning.

The nucleus accumbens shell in reinstatement and extinction of drug seeking

“…Finally, in the rostrocaudal plane, disrupting glutamatergic neurotransmission via infusions of an AMPA/Kainate receptor antagonist generates appetitively motivated behaviors (e.g., ingestion) in the rostral medial AcbSh but aversively motivated behaviors (e.g., defensive treading) in the caudal medial AcbSh (Reynolds & Berridge, , ). Interestingly, these rostrocaudal variations in valence are dopamine‐dependent (Faure et al ., ), consistent with other findings implicating AcbSh glutamate and dopamine neurotransmission in aspects of aversive learning and motivation (Li & McNally, ,b).…”

The nucleus accumbens core is necessary to scale fear to degree of threat

“…For example, the NAcc can modulate salience, regulating the ability of cues to enter into associations with shock (Iordanova et al, 2006b;Iordanova et al, 2006a;Iordanova, 2009). Human imaging studies have observed correlates of prediction error, a theoretical signal that strengthens or weakens cue-shock associations (Seymour et al, 2004;Delgado et al, 2008;Schiller et al, 2008;Li et al, 2011), consistent with a role for the NAcc in predictive learning (Li and McNally, 2015).…”

“…We identified the nucleus accumbens core (NAcc) as a likely candidate, based on its ability to rapidly process reward-predictive cues (Cromwell and Schultz, 2003;Setlow et al, 2003;Ambroggi et al, 2011;McGinty et al, 2013;Saddoris and Carelli, 2014;Sugam et al, 2014;Ottenheimer et al, 2018), as well as its anatomical connectivity with the amygdala (Kita and Kitai, 1990;Petrovich et al, 1996;Wright and Groenewegen, 1996). Even more, the NAcc is implicated in a variety of fear-related processes (Haralambous and Westbrook, 1999;Thomas et al, 2002;Schwienbacher et al, 2004;Iordanova et al, 2006a;Fadok et al, 2010;Badrinarayan et al, 2012;Oleson et al, 2012;Li and McNally, 2015;Correia et al, 2016).…”

Safety out of control: dopamine and defence

“…This is consistent with experimental results in appetitive Pavlovian conditioning reviewed above, which suggest that D 1 receptors are particularly important in learning the CS-US contingency, while both D 1 and D 2 receptors are involved in modulating expression of this learning. Further, it has been reported recently that disruption of dopamine signalling in NAcC, but not NAcS, attenuated the ability of an aversive CS to block secondary conditioning of an additional CS, suggesting differential involvement of these areas [ 278 ].…”