اداره درون هیپوکامپی از یک آنتاگونیست گیرنده NMDA باعث اختلال در آموزش معکوس تبعیض فضایی در نوازد موش می شود

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.

The N-methyl-d-Aspartate (NMDA) receptor subtype of glutamate receptors plays a substantial role in neural physiology, synaptic plasticity, and behavioral learning and memory. These roles include, but are not limited to, the molecular/cellular basis of short- and long-term memory formation, the induction and maintenance of long-term potentiation (LTP), as well spatial learning and memory that depends upon the hippocampus (Morris et al., 1986, O’Keefe and Nadel, 1978 and Shapiro, 2001). NMDA receptors are heavily concentrated in the hippocampal formation, cortex, and striatum (Wong et al., 1986 and Wong et al., 1988). These same brain regions are essential for spatial learning and memory, contextual memory, and higher-order cognitive learning tasks in adult animals. It is currently unknown if these same brain regions are involved in reversal learning during early ontogeny.