TY - JOUR
T1 - MK-801 and related compounds in monkeys
T2 - Discriminative stimulus effects and effects on a conditional discrimination
AU - France, C. P.
AU - Moerschbaecher, J. M.
AU - Woods, J. H.
PY - 1991
Y1 - 1991
N2 - MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] and related compounds were studied in monkeys discriminating between 0.032 mg/kg of (+)-MK-801 and saline and in a separate group of monkeys responding under a multiple schedule of repeated acquisition and performance of conditional discriminations. In the drug discrimination study, small doses of (+)-MK-801 occasioned saline-lever responding whereas larger doses occasioned responding on the MK-801 lever. Dexoxadrol substituted completely (≥90%) for the MK-801 discriminative stimulus in all subjects whereas dextrorphan and phencyclidine (PCP) substituted in only two of three subjects. Neither ketamine, (+)-N-allylnormetazocine, dextromethorphan nor the competitive excitatory amino acid antagonist CGS 19755 [cis-4-phosphonomethyl-2-piperidine-carboxylic acid] substituted for MK-801 in any of the monkeys. PCP, dextrorphan, dextromethorphan, (+)- and (-)-MK-801 decreased rates of lever pressing and increased errors in both components of the multiple acquisition, performance schedule. For each compound errors were increased in the acquisition component with doses smaller than doses required to increase errors in the performance component. In both procedures (+)-MK-801 was 10 times more potent than (-)-MK-801, although qualitatively similar results were obtained with the two enantiomers. PCP-like drugs have many effects in common, including their effects on learning and performance; however, with regard to discriminative stimulus effects this does not appear to be a homogenous pharmacological class, suggesting that change in excitatory amino acid-mediated neurotransmission might not be the only mechanism by which MK-801 and related compounds exert behavioral effects in nonhuman primates.
AB - MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate] and related compounds were studied in monkeys discriminating between 0.032 mg/kg of (+)-MK-801 and saline and in a separate group of monkeys responding under a multiple schedule of repeated acquisition and performance of conditional discriminations. In the drug discrimination study, small doses of (+)-MK-801 occasioned saline-lever responding whereas larger doses occasioned responding on the MK-801 lever. Dexoxadrol substituted completely (≥90%) for the MK-801 discriminative stimulus in all subjects whereas dextrorphan and phencyclidine (PCP) substituted in only two of three subjects. Neither ketamine, (+)-N-allylnormetazocine, dextromethorphan nor the competitive excitatory amino acid antagonist CGS 19755 [cis-4-phosphonomethyl-2-piperidine-carboxylic acid] substituted for MK-801 in any of the monkeys. PCP, dextrorphan, dextromethorphan, (+)- and (-)-MK-801 decreased rates of lever pressing and increased errors in both components of the multiple acquisition, performance schedule. For each compound errors were increased in the acquisition component with doses smaller than doses required to increase errors in the performance component. In both procedures (+)-MK-801 was 10 times more potent than (-)-MK-801, although qualitatively similar results were obtained with the two enantiomers. PCP-like drugs have many effects in common, including their effects on learning and performance; however, with regard to discriminative stimulus effects this does not appear to be a homogenous pharmacological class, suggesting that change in excitatory amino acid-mediated neurotransmission might not be the only mechanism by which MK-801 and related compounds exert behavioral effects in nonhuman primates.
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M3 - Article
C2 - 2033515
AN - SCOPUS:0025864533
SN - 0022-3565
VL - 257
SP - 727
EP - 734
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -