Discriminative stimulus properties of ketamine stereoisomers in phencyclidine-trained rats

Rats were trained to discriminate phencyclidine (PCP) from saline in a two-lever drug discrimination task on a fixed-ratio 32 schedule of food presentation. The subjects were given IP injections of 3.0 mg/kg PCP or saline daily on a double alternation schedule. After reliable discriminative control of lever choice was established, dose-response determinations for generalization to the training dose of PCP were made with several doses of PCP, a racemic mixture of ketamine and the pure levo (-) and dextro (+) salts of ketamine. All three forms of ketamine produced dose-dependent PCP-appropriate responding. ED50 values were determined for each drug for percent drug-lever appropriate responding and for suppression of operant responding during test sessions. There was a greater difference between doses which produced drug-lever appropriate responding and doses which suppressed response rates for PCP than for any of the forms of ketamine. (+/-)- and (+)-ketamine were about 2 times more potent than (-)-ketamine for producing drug-lever appropriate responding but were roughly equipotent for response rate suppression. Thus there is no qualitative and little quantitative stereospecificity for the PCP-like discriminative stimulus effects of ketamine in rats.