Effects of the N-methyl-D-aspartate receptor antagonist, MK-801, on spatial memory and influence of the route of administration.

Effects of the N-methyl-D-aspartate receptor antagonist, MK-801, on spatial memory and influence of the route of administration. Behav Brain Res. 2019 Jul 02;:112067 Authors: Svalbe B, Stelfa G, Vavers E, Zvejniece B, Grinberga S, Sevostjanovs E, Pugovics O, Dambrova M, Zvejniece L Abstract The N-methyl-D-aspartate receptor antagonist, MK-801, is widely used to induce memory and learning impairments in preclinical studies. MK-801 is mainly injected intraperitoneally (i.p.) at doses that result in cognitive impairment and induction of motor or sensory disturbances. The aim of this study was to compare the behavioral outcomes when different administration routes (subcutaneous (s.c.) and i.p.) and MK-801 doses (0.01, 0.05, and 0.1 mg/kg) are employed in the Morris water maze (MWM) task. We also assessed the pharmacokinetics of MK-801 in rat blood plasma and its bioavailability in brain tissue. The concentrations of MK-801 in brain tissue and blood plasma were significantly higher after s.c. than i.p. administration. MK-801 administered via the s.c. route at doses of 0.1 and 0.05 mg/kg significantly impaired learning on all training days in the MWM task compared to i.p. administration at the same doses. Memory in the probe trial was significantly impaired after MK-801 administration via both routes at all doses. MK-801 also induced locomotor disturbances after i.p. and s.c. administration at the highest dose (0.1 mg/kg). Our data suggest...
Source: Behavioural Brain Research - Category: Neurology Authors: Tags: Behav Brain Res Source Type: research

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