부산대학교 도서관

N-methyl-D-aspartate receptors (NMDARs) are essential for several kinds of synaptic plasticity and play a critical role in learning and memory. Deficits in NMDAR functioning may be partially responsible for the learning and memory deficits associated with aging and numerous diseases. Administration of MK-801, a noncompetitive NMDAR antagonist, is commonly used as a preclinical model of NMDAR dysfunction. The objective of this study was to assess the effects of 5GABAAreceptor inhibition on learning deficits in the incremental repeated acquisition (IRA) task induced by acute MK-801 administration. The IRA task, commonly used to examine factors that affect learning, begins with a single response and increments to progressively longer chains throughout a single session as behavior meets preset criteria. MK-801 (0.03–0.5 mgkg, intraperitoneally), administered 10 min pretesting, produced a significant dose-dependent decrease in measures of IRA performance at doses greater than or equal to 0.25 mgkg. The MK-801-induced deficit was attenuated after treatment with an 5GABAAreceptor inverse agonist, L-655,708 (1 mgkg, intraperitoneally). The present study provides the focus for, and supports the feasibility of, further in-depth definitive studies examining 5GABAAreceptor inhibition as a suitable candidate for the attenuation of NMDAR-related deficits.