Interactive effect of MK-801 and pre-training on spatial learning in rats

Abstract

In experiment 1, the effect of an NMDA receptor antagonist, MK-801, on the formation of the spatial representation was investigated. The administration of 0.1 mg/kg of MK-801 induced learning deficits in rats (n = 10) with the Morris watermaze task. However, when rats (n = 10) were pre-trained in the same task without drug treatment, and then trained in the same task in a different environment under the influence of the same amount of the drug, their performance was not impaired. The result suggests that rats treated with MK-801 can acquire a spatial representation of their environment, and that the impairment shown by the drug-treated rats without pre-training may be due to the impairment in the learning of the problem-solving strategy required for the watermaze place task. Experiment 2 examined this possibility. Rats (n = 10) were pre-trained with a visual cue discrimination task without drug treatment and then trained in the place task with MK-801 (0.1 mg/kg) treatment. They did not show impairment in the place task, indicating that rats treated with MK-801 can learn a new problem-solving strategy. Thus the learning deficits of MK-801-treated rats that have not been pre-trained do not seem to be due to impaired acquisition of the spatial representation or of the learning of strategy required to solve the watermaze place task.