Intrahippocampal administration of an NMDA-receptor antagonist impairs spatial discrimination reversal learning in weanling rats

Systemic administration of MK-801, an NMDA-receptor antagonist, impairs reversal learning in weanling rats [Chadman, K.K., Watson, D.J., & Stanton, M.E. (2006). NMDA-receptor antagonism impairs reversal learning in developing rats. Behavioral Neuroscience, 120(5), 1071–1083]. The brain systems responsible for this effect are not known in either adult or young animals. This study tested the hypothesis that hippocampal NMDA receptors are engaged in weanling-age rats during spatial discrimination reversal training in a T-maze. In Experiment 1, 26-day-old Long-Evans rats (P26) showed a dose-related impairment on this task following bilateral intrahippocampal administration of either 2.5 or 5.0 μg MK-801 or saline vehicle during the reversal training phase only. In Experiment 2, P26 rats were trained on the same task, but received intrahippocampal MK-801 (2.5 μg) during acquisition, reversal, both, or neither. MK-801 failed to impair acquisition, ruling out nonspecific “performance effects” of the drug. MK-801 impaired reversal irrespective of drug treatment during acquisition. NMDA-receptor antagonism in the hippocampus is sufficient to account for the previously reported effects of systemic MK-801 on reversal of T-maze position discrimination.