Hyperactivity, hyper-reactivity, and sensorimotor deficits induced by low doses of the N-methyl-D-aspartate non-competitive channel blocker MK801.
Three doses of MK801 (0.05 mg/kg, 0.3 mg/kg and 1.0 mg/kg) were given systemically to adult male rats, which were then tested on a battery of previously learned, reactive and spontaneous behaviors. Hyperactivity, hyper-reactivity, reductions in rearing behavior and deficits in tongue extension were found at the 0.05 mg/kg dose. Similar, but more severe results were found at the 0.3 mg/kg dose, with the addition of difficulties in climbing, balancing on a beam, and abnormalities in orienting to tactile stimuli. A number of tasks could not be performed at the 1.0 mg/kg dose including tongue extension, orienting, balancing on a beam, and climbing. Additionally, abnormal postures, gaits, and swimming behaviors were observed at this dose. These results characterize the behavioral effects of MK801 as a syndrome of hyperactivity, hyper-reactivity, and sensorimotor deficits. Evidence of this syndrome was present at all three doses, including the 0.05 mg/kg dose, which previously has been claimed to induce deficits similar to hippocampal lesions. Learning literature employing MK801 is discussed in the context of the behavioral deficits found in this study.
Hargreaves
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Department of Psychology, University of Western Ontario, London, Canada.
Cain
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DP
D000818:Animals; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005247:Feeding Behavior / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009048:Motor Skills / Q000187:drug effects*; D009473:Neuronal Plasticity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects; D009949:Orientation / Q000187:drug effects*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D009435:Synaptic Transmission / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate