ANTAGONISM OF A NICOTINE PLUS MIDAZOLAM DISCRIMINATIVE CUE IN RATS

Rats were trained to discriminate nicotine (0.4 mg/kg s.c.), midazolam (0.2 mg/kg s.c.) or the combination of these drugs from saline (n = 1 0). The rats were trained to 95% accuracy in a two-bar operant procedu re with a tandem schedule of food reinforcement. Testing with the indi vidual drugs in the mixture-trained group showed that nicotine (85% dr ug-appropriate responding) was a more salient component than midazolam (47%) in the compound stimulus. The rats were tested with benzodiazep ine and nicotine antagonists individually and in combination (mecamyla mine 0.2-1.6 mg/kg s.c.; flumazenil 2.5-20 mg/kg i.p.). Results for th e mixture-trained animals shelved that flumazenil had no effect on its own, however mecamylamine on its own produced a significant but incom plete block in doses of 0.4-1.6 mg/kg. The greater salience of the nic otine component of the cue would explain the block by mecamylamine but not flumazenil. The antagonists in combination produced greater block ade than mecamylamine on its own. The selectivity of the antagonist ac tions on the different cue components was also demonstrated. The resul ts suggest that in drug discrimination experiments, ''false negative'' results may be obtained with antagonists when a training drug produce s a stimulus with more than one component.