Drug trace discrimination with nicotine and morphine in rats

In typical drug discrimination experiments, subjects are exposed to psychoactive substances both prior to and during training sessions. The present experiments aimed to determine whether pre-session effects of drugs could serve as discriminative stimuli. Rats were trained in a two-lever discrimination procedure with food reinforcers presented on a tandem variable interval-fixed ratio (VI-FR) schedule. Injections of nicotine (0.6mg/kg 20 min pre-session) or saline were followed by administration of the nicotine antagonist mecamylamine (1.0 mg/kg 10 min pre-session) to block effects of nicotine during training sessions. Similarly, the action of morphine (10 mg/kg 30 min pre-session) was terminated by administering naloxone (0.1 mg/kg 10 min pre-session). These drug discriminations were acquired slowly to an accuracy of only 70-75% (n=10-12). Extinction tests confirmed stimulus control by nicotine in the presence of mecamylamine and by morphine in the presence of naloxone. The antagonists attenuated the response-rate reducing effects of the training doses of their respective agonists. The results are interpreted in terms of stimulus control by pre-session effects of the training drugs, but other explanations are considered. Stimulus control by pre-session drug states may be weak due to the time elapsed between termination of drug effects and training (trace conditioning).