Effects of MK-801 stereoisomers on schedule-controlled behavior in rats.
Behavioral effects of (+)MK-801 (0.03-0.32 mg/kg) and (-)MK-801 (0.32-3.20 mg/kg) were evaluated in rats using a multiple fixed-ratio, fixed-interval (FR20, FI2) schedule of food presentation. Both enantiomers produced dose-dependent decreases in response rate under the FR20 and in this respect (+)MK-801 was approximately ten times as potent as (-)MK-801. Under the FI2 schedule component, the (+) enantiomer produced substantial increases as well as decreases in response rate whereas the (-) enantiomer produced only decreases. When 0.178 mg/kg (+)MK-801 and 1.78 mg/kg (-)MK-801 were administered for 11 consecutive days, tolerance developed to the decrease in response rate under the FR20 schedule component. Tolerance to the effects of the (+) enantiomer under the FI2 schedule component was indicated by progressively larger increases in response rate than those observed during acute administration. These results support potential therapeutic applications of MK-801.
Genovese
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RF
Department of Medical Neurosciences, Walter Reed Army Institute of Research, Washington, D.C. 20307-5100.
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XC
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule; D013237:Stereoisomerism
D016291:Dizocilpine Maleate