Relative reinforcing strength of three N-methyl-D-aspartate antagonists with different onsets of action

G. Winger, S. R. Hursh, K. L. Casey, J. H. Woods

Research output: Contribution to journalArticlepeer-review

71 Scopus citations


The potential contribution of onset and duration of pharmacological action to the reinforcing strength of three intravenously delivered N-methyl-D-aspartate antagonists was evaluated in this study. The onsets and durations of action of ketamine, phencyclidine, and dizocilpine were evaluated by observation and tabulation of their behavioral effects in rhesus monkeys after i.v. administration. The reinforcing effects of each drug were tested in a paradigm in which the fixed ratio requirements for i.v. drug injection were increased systematically. The peak observable effect of ketamine occurred immediately after its administration. There were some immediately observable effects of phencyclidine, although the peak effect of phencyclidine was delayed for 3 to 10 min. Dizocilpine had few immediate effects and a peak effect 32 min after administration. Ketamine had the shortest duration of action, followed by phencyclidine and dizocilpine. Analysis of demand curves and response output curves that were normalized to account for potency differences among the drugs revealed that ketamine and phencyclidine were equally effective as reinforcers, and they were both much stronger reinforcers than was dizocilpine. The data therefore suggest that a fast onset of action increases the reinforcing strength of drugs, although duration of action may play a role as well.

Original languageEnglish (US)
Pages (from-to)690-697
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number2
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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