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MK-801 and related compounds in monkeys: discriminative stimulus effects and effects on a conditional discrimination.
J Pharmacol Exp Ther. 1991 May; 257(2):727-34.JP

Abstract

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 (greater than or equal to 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.

Authors+Show Affiliations

Department of Pharmacology, University of Michigan, Ann Arbor.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

2033515

Citation

France, C P., et al. "MK-801 and Related Compounds in Monkeys: Discriminative Stimulus Effects and Effects On a Conditional Discrimination." The Journal of Pharmacology and Experimental Therapeutics, vol. 257, no. 2, 1991, pp. 727-34.
France CP, Moerschbaecher JM, Woods JH. MK-801 and related compounds in monkeys: discriminative stimulus effects and effects on a conditional discrimination. J Pharmacol Exp Ther. 1991;257(2):727-34.
France, C. P., Moerschbaecher, J. M., & Woods, J. H. (1991). MK-801 and related compounds in monkeys: discriminative stimulus effects and effects on a conditional discrimination. The Journal of Pharmacology and Experimental Therapeutics, 257(2), 727-34.
France CP, Moerschbaecher JM, Woods JH. MK-801 and Related Compounds in Monkeys: Discriminative Stimulus Effects and Effects On a Conditional Discrimination. J Pharmacol Exp Ther. 1991;257(2):727-34. PubMed PMID: 2033515.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MK-801 and related compounds in monkeys: discriminative stimulus effects and effects on a conditional discrimination. AU - France,C P, AU - Moerschbaecher,J M, AU - Woods,J H, PY - 1991/5/1/pubmed PY - 2000/6/1/medline PY - 1991/5/1/entrez SP - 727 EP - 34 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 257 IS - 2 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 (greater than or equal to 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. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2033515/MK_801_and_related_compounds_in_monkeys:_discriminative_stimulus_effects_and_effects_on_a_conditional_discrimination_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2033515 DB - PRIME DP - Unbound Medicine ER -