NMDA receptor antagonist MK-801 selectively impairs learning of the contiguity of the conditioned stimulus and unconditioned stimulus in goldfish.

Previous experiments have shown that administration of intracranial MK-801 blocks learning of classical fear conditioning in goldfish. The impairment of learning was decreased when fish received limited pretraining, suggesting that only the early phase of conditioning may be sensitive to disruption by MK-801. The present studies investigated the possibility that classical conditioning in goldfish consists of two successive phases and that only the initial phase depends critically on N-methyl-D-aspartate receptor function. A series of experiments showed that the anterograde amnestic effect of MK-801 is decreased or eliminated when fish received pretraining consisting of 6 or 12 conditioning trials, respectively. MK-801-sensitive learning is inferred to be completed within 12 trials. The neural mechanism of the learning which occurs during the later trials is manifestly insensitive of MK-801. Furthermore, MK-801 impaired learning when fish received pretraining consisting of six pseudoconditioning trials. The results indicate that MK-801-sensitive learning is associative or depends on the contiguity of the conditioned stimulus (CS) and unconditioned stimulus (US) and that MK-801 selectively impairs learning of the CS-US contiguity.