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The self-administration of MK-801 can depend upon drug-reinforcement history, and its discriminative stimulus properties are phencyclidine-like in rhesus monkeys.
J Pharmacol Exp Ther. 1990 Mar; 252(3):953-9.JP

Abstract

The proposed noncompetitive N-methyl-D-aspartate antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate] has therapeutic potential as an anticonvulsant and neuroprotectant. Previous research has demonstrated that MK-801 shares many of the biochemical and pharmacological actions of the abused drug phencyclidine (PCP). The purpose of the present study was to determine whether rhesus monkeys would self-administer i.v. MK-801 and to determine whether MK-801 has discriminative stimulus properties similar to those of PCP. Four Rhesus monkeys were trained to press response levers according to fixed-ratio 10 schedules of reinforcement for infusions of cocaine (33 micrograms/kg/injection) or PCP (10 micrograms/kg/injection). Various doses of MK-801 were evaluated during substitution tests to determine whether they would maintain lever pressing. None of the four rhesus monkeys tested self-administered MK-801 when it was offered to them after a recent history of cocaine self-administration. Three of the four monkeys, however, did self-administer MK-801 when provided a history of PCP self-administration. All four rhesus monkeys given drug discrimination training with 80 micrograms/kg PCP and tested with MK-801 generalized from the PCP stimulus in a dose-dependent manner. MK-801 was about 2 to 3 times more potent and had a longer duration of action than PCP. Overall, these results provide further evidence in a primate species of similarities in the behavioral effects of MK-801 and PCP, and suggest that MK-801 may have abuse potential of the PCP type.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0613.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

2181113

Citation

Beardsley, P M., et al. "The Self-administration of MK-801 Can Depend Upon Drug-reinforcement History, and Its Discriminative Stimulus Properties Are Phencyclidine-like in Rhesus Monkeys." The Journal of Pharmacology and Experimental Therapeutics, vol. 252, no. 3, 1990, pp. 953-9.
Beardsley PM, Hayes BA, Balster RL. The self-administration of MK-801 can depend upon drug-reinforcement history, and its discriminative stimulus properties are phencyclidine-like in rhesus monkeys. J Pharmacol Exp Ther. 1990;252(3):953-9.
Beardsley, P. M., Hayes, B. A., & Balster, R. L. (1990). The self-administration of MK-801 can depend upon drug-reinforcement history, and its discriminative stimulus properties are phencyclidine-like in rhesus monkeys. The Journal of Pharmacology and Experimental Therapeutics, 252(3), 953-9.
Beardsley PM, Hayes BA, Balster RL. The Self-administration of MK-801 Can Depend Upon Drug-reinforcement History, and Its Discriminative Stimulus Properties Are Phencyclidine-like in Rhesus Monkeys. J Pharmacol Exp Ther. 1990;252(3):953-9. PubMed PMID: 2181113.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The self-administration of MK-801 can depend upon drug-reinforcement history, and its discriminative stimulus properties are phencyclidine-like in rhesus monkeys. AU - Beardsley,P M, AU - Hayes,B A, AU - Balster,R L, PY - 1990/3/1/pubmed PY - 1990/3/1/medline PY - 1990/3/1/entrez SP - 953 EP - 9 JF - The Journal of pharmacology and experimental therapeutics JO - J. Pharmacol. Exp. Ther. VL - 252 IS - 3 N2 - The proposed noncompetitive N-methyl-D-aspartate antagonist MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate] has therapeutic potential as an anticonvulsant and neuroprotectant. Previous research has demonstrated that MK-801 shares many of the biochemical and pharmacological actions of the abused drug phencyclidine (PCP). The purpose of the present study was to determine whether rhesus monkeys would self-administer i.v. MK-801 and to determine whether MK-801 has discriminative stimulus properties similar to those of PCP. Four Rhesus monkeys were trained to press response levers according to fixed-ratio 10 schedules of reinforcement for infusions of cocaine (33 micrograms/kg/injection) or PCP (10 micrograms/kg/injection). Various doses of MK-801 were evaluated during substitution tests to determine whether they would maintain lever pressing. None of the four rhesus monkeys tested self-administered MK-801 when it was offered to them after a recent history of cocaine self-administration. Three of the four monkeys, however, did self-administer MK-801 when provided a history of PCP self-administration. All four rhesus monkeys given drug discrimination training with 80 micrograms/kg PCP and tested with MK-801 generalized from the PCP stimulus in a dose-dependent manner. MK-801 was about 2 to 3 times more potent and had a longer duration of action than PCP. Overall, these results provide further evidence in a primate species of similarities in the behavioral effects of MK-801 and PCP, and suggest that MK-801 may have abuse potential of the PCP type. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/2181113/The_self_administration_of_MK_801_can_depend_upon_drug_reinforcement_history_and_its_discriminative_stimulus_properties_are_phencyclidine_like_in_rhesus_monkeys_ L2 - http://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=2181113 DB - PRIME DP - Unbound Medicine ER -