NMDA and AMPA antagonist infusions into the ventral striatum impair different steps of spatial information processing in a nonassociative task in mice

Abstract

Most of the research on ventral striatal functions has been focused on their role in modulating reward and motivation. More recently, a possible role of this structure in cognitive functions has been suggested. However, very little information is available on the involvement of the nucleus accumbens in the different stages of the consolidation process. In this study, the effect of focal injections of AP-5 and DNQX, competitive antagonists at the NMDA and AMPA receptors, respectively, was examined in a nonassociative task designed to estimate the ability of mice to react to spatial changes. The task consists of placing the animals in an open field containing five objects; after three sessions of habituation, their reactivity to object displacement was examined 24 hr later. AP-5 injections administered after training impaired the ability of mice to detect the spatial novelty but did not affect response when injected 120 min after training or before testing. On the contrary, DNQX did not affect response when administered immediately or 120 min after training but did impair spatial discrimination when administered before training or testing. These data demonstrate a double dissociation between glutamate receptor subtypes, such that accumbens NMDA receptors are important for consolidation and not ongoing discrimination of spatial information, whereas AMPA receptors have an opposite role in these processes.

Fig. 1.

Schematic representation of the apparatus and the object configuration over successive sessions. A, The open field is initially empty (S1); in the three subsequent sessions (S2–S4), it is filled with objects in a particular configuration (B). In S5, two objects are displaced (spatial novelty) (C).

Fig. 2.

Drawing of coronal sections from animals in all experiments. Each symbol represents the cannula placement.A, Immediate post-training AP-5 administrations.Filled triangles, saline; open circles, AP-5 at 0.07 μg/side; filled circles, AP-5 at 0.15 μg/side; filled diamonds, AP-5 at 0.3 μg/side.B, Immediate post-training DNQX administrations.Filled triangles, vehicle; open andfilled circles, respectively, AMPA antagonist at 0.001 and 0.005 μg/side. C, Cannula placements for administrations of vehicle (filled triangles), AP-5 at 0.03 μg/side (open circles), and DNQX at 0.005 μg/side (filled circles) 120 min after training. D, Cannula placements for mice administered vehicle (filled triangles), AP-5 at 0.15 μg/side (open circles), and DNQX at 0.001 μg/side (filled circles) before testing.E, Cannula placements for mice administered vehicle (filled triangles) and DNQX at 0.001 μg/side (open circles) before training.

Fig. 3.

Experiment 1: Reactivity to spatial change of mice after immediate post-training focal administration of AP-5 into the nucleus accumbens. The histogram illustrates the mean time (± SEM) spent exploring the DO or NDO in S5 minus the time spent exploring the same class of objects in the last session of habituation (S4). *p < 0.05; DO versus NDO.

Fig. 4.

Experiment 2: Reactivity to spatial change of mice after immediate post-training focal administration of the AMPA antagonist DNQX into the nucleus accumbens. The histogram illustrates the mean time (± SEM) spent exploring the DO or NDO in S5 minus the time spent exploring the same class of objects in the last session of habituation (S4). *p < 0.05; DO versus NDO.

Fig. 5.

Experiment 3: Reactivity to spatial change of mice after post-training focal administration of AP-5 at 0.03 μg/side and DNQX at 0.005 μg/side into the nucleus accumbens 120 min after S4. The histogram illustrates the mean time (± SEM) spent exploring the DO or NDO in S5 minus the time spent exploring the same class of objects in the last session of habituation (S4). *p < 0.05; DO versus NDO.

Fig. 6.

Experiment 4: Reactivity to spatial change of mice after pretest focal administration of AP-5 at 0.015 μg/side and DNQX at 0.001 μg/side into the nucleus accumbens. The histogram illustrates the mean time (± SEM) spent exploring the DO or NDO in S5 minus the time spent exploring the same class of objects in the last session of habituation (S4). *p < 0.05; DO versus NDO.

Fig. 7.

Experiment 5: Reactivity to spatial change of mice after pretraining focal administration of DNQX at 0.001 μg/side into the nucleus accumbens. The histogram illustrates the mean time (± SEM) spent exploring the DO or NDO in S5 minus the time spent exploring the same class of objects in the last session of habituation (S4). *p < 0.05; DO versus NDO.