Differential Involvement of NMDA, AMPA/Kainate, and Dopamine Receptors in the Nucleus Accumbens Core in the Acquisition and Performance of Pavlovian Approach Behavior

TLDR

Pavlovian approach responses are mediated by the nucleus accumbens, and receptor interactions within this region influence the acquisition and expression of conditioned approach behavior. The study examined how blocking glutamatergic or dopaminergic receptors in the nucleus accumbens core affects acquisition and performance of discriminated Pavlovian approach to a lever cue. Rats were trained on an autoshaping task with a lever CS+ paired with food and a CS− never paired, and then received infusions of NMDA, AMPA/kainate, or dopamine receptor antagonists into the nucleus accumbens core. Infusions produced a triple dissociation: the NMDA antagonist AP‑5 impaired acquisition only, the AMPA/kainate antagonist LY293558 disrupted performance only, and the dopamine antagonist α‑flupenthixol reduced CS+ approaches during both acquisition and performance.

Abstract

Stimuli paired with primary rewards can acquire emotional valence and the ability to elicit automatic, Pavlovian approach responses that have been shown to be mediated by the nucleus accumbens. The present experiment investigated the effects of infusions of glutamatergic or dopaminergic receptor antagonists into the core of the nucleus accumbens on the acquisition and performance of Pavlovian discriminated approach to an appetitive conditioned stimulus. Rats were trained on an autoshaping task in which a conditioned stimulus (CS+; a lever) was inserted into the operant chamber for 10 sec, after which a food pellet was delivered. Presentation of another lever (CS−) was never followed by food. Subjects developed a conditioned response of approaching and contacting the CS+ selectively, although food delivery was not in any way contingent on the animals9 response. A triple dissociation in the effects of AP-5, LY293558 [(3<i>SR</i>, 4a<i>RS</i>, 6<i>RS</i>, 8a<i>RS</i>)-6-[2-(iH-tetrazol-5-yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroiso-quinoline-3-carboxylic acid], and α-flupenthixol infused into the nucleus accumbens core on the acquisition and performance of this conditioned response was observed. The AMPA/kainate receptor antagonist LY293558 disrupted discriminated approach performance but not acquisition, as evidenced by increased approaches to the CS−. In contrast, the NMDA receptor antagonist AP-5 impaired only the acquisition, but not performance, of autoshaping whereas the dopamine D1/D2 receptor antagonist α-flupenthixol decreased approaches to the CS+ during both acquisition and performance. The data are discussed with reference to dissociable interactions of these receptor types with limbic cortical and dopaminergic afferents to the nucleus accumbens core during the acquisition and expression of Pavlovian conditioned approach.