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.