Dopamine Receptor Agonism in the Nucleus Accumbens Shell During Aversive Learning or Memory Retrieval: Differential Effects Depending on the Degree of Sugar Familiarity

ABSTRACT Sugar provides energy and activates several processing pathways, including the reward and memory systems, both of which are essential for feeding behavior and modulating the amount and frequency of consumption. Accordingly, the conditioned taste aversion (CTA) model allows the study of the underlying mechanisms of flavor processing and aversive learning, as well as the phenomenon of latent inhibition (LI) of CTA. It has previously been demonstrated that the nucleus accumbens, particularly the core region, is required for appetitive and aversive taste learning. However, recent evidence suggests that the nucleus accumbens shell (NACsh) is involved in the transition and updating of appetitive memories. The present study evaluated changes in NACsh dopamine receptor function during aversive learning (CTA) and during memory retrieval, assessing their role as a function of the degree of sugar familiarity (e.g., LI of CTA). To this end, we evaluated the effect of agonist apomorphine injections into the NACsh during acquisition and memory retrieval of CTA, as well as during the LI of CTA after rats became familiar (3 days, S3d) or highly familiar (24 days, S24d) with sugar. The results indicated that dopaminergic agonism in the NACsh impairs the appetitive response to novel sugar without affecting CTA, but it also accelerates aversive memory extinction. Moreover, when dopamine receptor activation occurred after a few isolated sugar consumptions (S3d), it did not affect the LI of CTA. However, if the same activation occurred after weeks of permanent sugar consumption (S24d), the LI of CTA increased significantly, and the appetitive sugar response was also enhanced in subsequent presentations. Furthermore, apomorphine injections before CTA retrieval significantly delay aversive memory extinction without affecting aversive recall or the LI of CTA, regardless of familiarity. This work helps elucidate the modulatory role of dopaminergic activity in the NACsh during familiarization with a highly hedonic stimulus and its update during aversive conditioning and memory retrieval.