Differential involvement of NMDA, AMPA/kainate, and dopamine receptors in the nucleus accumbens core in the acquisition and performance of pavlovian approach behavior - PubMed (original) (raw)

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

P Di Ciano et al. J Neurosci. 2001.

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 animals' response. A triple dissociation in the effects of AP-5, LY293558 [(3SR, 4aRS, 6RS, 8aRS)-6-[2-(iH-tetrazol-5-yl)ethyl]-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 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 alpha-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.

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Figures

Fig. 1.

Fig. 1.

Location of the tips of injection cannulas within the NAcc core for the performance (A) and acquisition (B) experiments.Symbols represent the bilateral placement of the injections for individual animals. Schematics of coronal sections are taken from Paxinos and Watson (1986).

Fig. 2.

Fig. 2.

Effects of infusion of vehicle (A), the AMPA/KA antagonist LY293558 (0.02 μg) (B), the DA antagonist α-flupenthixol (10 μg) (C), and the NMDA antagonist AP-5 (1 μg) (D) on the acquisition of autoshaping. Day × stimulus interaction: for vehicle, p < 0.001; for LY293558, p < 0.001. *indicates days at which approach to the two levers was significantly different;p < 0.05 (planned comparisons).

Fig. 3.

Fig. 3.

Acquisition of autoshaping. _Filled_and open symbols represent the probability of approach to the CS+ and CS− stimuli, respectively. Squares,triangles, and diamonds represent the LY293558, AP-5, and α-flupenthixol treatment groups, respectively, that the rats were assigned to after acquisition. Day × stimulus interaction, p < 0.001.

Fig. 4.

Fig. 4.

The effects of infusion of the AMPA/KA antagonist LY293558 (A), the DA antagonist α-flupenthixol (B), and the NMDA antagonist AP-5 (C) on the performance of Pavlovian discriminated approach. Filled and _open symbols_represent the probability of approach to the CS+ and CS− stimuli, respectively. Dose × stimulus interaction: for LY293558,p = 0.008; for flupenthixol, _p_= 0.002.

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