Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of Pavlovian approach behavior

Stimuli paired with primary rewards can acquire emotional valence and the a bility to elicit automatic, Pavlovian approach responses that have been sho wn to be mediated by the nucleus accumbens. The present experiment investig ated the effects of infusions of glutamatergic or dopaminergic receptor ant agonists into the core of the nucleus accumbens on the acquisition and perf ormance of Pavlovian discriminated approach to an appetitive conditioned st imulus. Rats were trained on an autoshaping task in which a conditioned sti mulus (CS+; a lever) was inserted into the operant chamber for 10 sec, afte r which a food pellet was delivered. Presentation of another lever (CS-) wa s never followed by food. Subjects developed a conditioned response of appr oaching and contacting the CS+ selectively, although food delivery was not in any way contingent on the animals' response. A triple dissociation in th e effects of AP-5, LY293558 [(3SR, 4aRS, 6RS, 8aRS)-6-[2-(iH-tetrazol-5yl)e thyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroiso-quinoline-3-carboxylic acid], and alpha -flupenthixol infused into the nucleus accumbens core on the acquisit ion and performance of this conditioned response was observed. The AMPA/kai nate receptor antagonist LY293558 disrupted discriminated approach performa nce but not acquisition, as evidenced by increased approaches to the CS-. I n contrast, the NMDA receptor antagonist AP-5 impaired only the acquisition , but not performance, of autoshaping whereas the dopamine D1/D2 receptor a ntagonist alpha -flupenthixol decreased approaches to the CS+ during both a cquisition and performance. The data are discussed with reference to dissoc iable interactions of these receptor types with limbic cortical and dopamin ergic afferents to the nucleus accumbens core during the acquisition and ex pression of Pavlovian conditioned approach.