A DOSE OF MK801 PREVIOUSLY SHOWN TO IMPAIR SPATIAL-LEARNING IN THE RADIAL MAZE ATTENUATES PRIMED BURST POTENTIATION IN THE DENTATE GYRUS OFFREELY MOVING RATS

Spatial learning but not memory performance in the radial maze is disr upted by low doses of MK801 (0.0625 mg/kg ip), a noncompetitive N-meth yl-D-aspartate receptor channel blocker (M. L,. Shapiro & C. O'Connor, 1992). The effect of this low dose of MK801 on hippocampal physiology and synaptic plasticity was assessed in 16 behaving female Sprague-Da wley rats. The drug increased the frequency (0.5 Hz), marginally reduc ed the amplitude of hippocampal rhythmical slow wave activity (RSA), d id not alter non-RSA slow wave activity, and reduced normal synaptic t ransmission from the entorhinal cortex to the dentate gyms by similar to 8%. Independent of these effects on normal physiology, MK-801 also reduced primed burst potentiation, a form of synaptic plasticity produ ced by physiologically patterned stimulation, by similar to 20% in the same pathway. Thus, low doses of MK801 may impair spatial learning by reducing, directly or indirectly, the likelihead of synaptic plastici ty in the hippocampus.