A dose of MK801 previously shown to impair spatial learning in the radial maze attenuates primed burst potentiation in the dentate gyrus of freely moving rats.
Spatial learning but not memory performance in the radial maze is disrupted by low doses of MK801 (0.0625 mg/kg ip), a noncompetitive N-methyl-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-Dawley rats. The drug increased the frequency (0.5 Hz), marginally reduced the amplitude of hippocampal rhythmical slow wave activity (RSA), did not alter non-RSA slow wave activity, and reduced normal synaptic transmission from the entorhinal cortex to the dentate gyrus by approximately 8%. Independent of these effects on normal physiology. MK-801 also reduced primed burst potentiation, a form of synaptic plasticity produced by physiologically patterned stimulation, by approximately 20% in the same pathway. Thus, low doses of MK801 may impair spatial learning by reducing, directly or indirectly, the likelihood of synaptic plasticity in the hippocampus.
Hargreaves
E L
EL
Department of Psychology, McGill University, Montreal, Quebec, Canada. erk@blaise.psych.mcgill.ca
Côte
D
D
Shapiro
M L
ML
D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007274:Injections, Intraperitoneal; D017774:Long-Term Potentiation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects; D009949:Orientation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects*
D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate