Time-limited modulation of appetitive Pavlovian memory by D1 and NMDA receptors in the nucleus accumbens

Abstract

Recent research has implicated the nucleus accumbens (NAc) in consolidating recently acquired goal-directed appetitive memories, including spatial learning and other instrumental processes. However, an important but unresolved issue is whether this forebrain structure also contributes to the consolidation of fundamental forms of appetitive learning acquired by Pavlovian associative processes. In addition, although dopaminergic and glutamatergic influences in the NAc have been implicated in instrumental learning, it is unclear whether similar mechanisms operate during Pavlovian conditioning. To evaluate these issues, the effects of posttraining intra-NAc infusions of D1, D2, and NMDA receptor antagonists, as well as d-amphetamine, were determined on Pavlovian autoshaping in rats, which assesses learning by discriminated approach behavior to a visual conditioned stimulus predictive of food reward. Intracerebral infusions were given either immediately after each conditioning session to disrupt early memory consolidation or after a delay of 24 h. Findings indicate that immediate, but not delayed, infusions of both D1 (SCH 23390) and NMDA (AP-5) receptor antagonists significantly impair learning on this task. By contrast, amphetamine and the D2 receptor antagonist sulpiride were without significant effect. These findings provide the most direct demonstration to date that D1 and NMDA receptors in the NAc contribute to, and are necessary for, the early consolidation of appetitive Pavlovian learning.

Fig. 1.

Schematic illustration of the experimental protocol. The acquisition of autoshaping was conducted over three sessions, each consisting of 50 trials with an intersession interval of 72 h. The highlighted boxes indicate the timing of the drug infusions in the NAc. These occurred either immediately after each conditioning session (condition A) or after a delay of 24 h (condition B). P denotes a probe retention test; O denotes omission training.

Fig. 2.

Diagrammatic sections modified from the atlas of Paxinos and Watson (23) showing injector tip placements in the vicinity of the NAc. The numbers to the right of each section are anterior coordinates forward of bregma (in mm).

Fig. 3.

Impaired Pavlovian learning as a consequence of immediate postsession intra-NAc infusions of the D1 receptor antagonist SCH 23390 (0.3 μg per side) and the NMDA receptor antagonist AP-5 (1 μg per side). Delayed infusions of the same compounds produced no significant effect. Discriminated approach to the visual stimulus predictive (CS+) and nonpredictive (CS-) of food reward was evaluated over 15 blocks, each consisting of 10 discrete trials. The maximum number of CS+ or CS- approach responses for each block was 10. Error bars represent ±1 SEM.

Fig. 4.

Inflexible CS+ approach during omission training, where reinforcement was made contingent on the nonoccurrence of a CS+ directed response. A failure to extinguish responding to the CS+ during this procedure indicates that appetitive learning was supported mainly by Pavlovian associative mechanisms. Error bars represent ±1 SEM.