RT Journal Article
SR Electronic
T1 Relative Reinforcing Strength of ThreeN-Methyl-d-Aspartate Antagonists with Different Onsets of Action
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 690
OP 697
DO 10.1124/jpet.301.2.690
VO 301
IS 2
A1 G. Winger
A1 S. R. Hursh
A1 K. L. Casey
A1 J. H. Woods
YR 2002
UL http://jpet.aspetjournals.org/content/301/2/690.abstract
AB The potential contribution of onset and duration of pharmacological action to the reinforcing strength of three intravenously deliveredN-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. The American Society for Pharmacology and Experimental Therapeutics