IMPACT OF TRAINING HISTORY ON DISCRIMINATION OF A DRUG MIXTURE BY RATS

The impact of training sequence on discrimination of a mixture of two drugs was investigated with five groups of rats (n = 10). In phase I, two groups were trained according to conventional two-lever, operant d rug discrimination protocols with food reinforcement; one of these gro ups was trained with nicotine (0.4 mg/kg) and the other group was trai ned with midazolam (0.15 mg/kg). The three remaining groups served as controls and were subjected to 'sham' training in which administration s of saline, nicotine or midazolam were unrelated to contingencies of reinforcement. After completion of phase I (40 sessions), all five gro ups were trained to discriminate a mixture of nicotine (0.4 mg/kg) plu s midazolam (0.15 mg/ kg) from saline (phase II). Any differences betw een the groups in their performance during phase II could, therefore, be attributed to their different histories in phase I. During phase II , all groups discriminated the mixture from saline with similar accura cy (89-94% drug-appropriate responding after mixture as compared with 2-7% after saline). In the three groups of rats subjected to 'sham' tr aining in phase I, there was partial generalization to both nicotine ( 45-53%) and midazolam (39-40%), each of which therefore contributed ab out equally to stimulus control by the mixture. In rats that were init ially trained to discriminate nicotine, midazolam had acquired little stimulus control over behaviour (9%) and discrimination of the mixture was attributable largely to the nicotine (87%). Conversely, in rats t hat were initially trained to discriminate midazolam, nicotine contrib uted 3% and midazolam 76% to stimulus control by the mixture. These po werful, persistent effects of training sequence were interpreted as ex amples of associative blocking demonstrated with the interoceptive sti muli produced by psychoactive drugs.