Differential sensitivity to midazolam discriminative-stimulus effects following self-administered versus response-independent midazolam.

Interactions between the discriminative and reinforcing effects of midazolam were studied in two baboons trained to discriminate midazolam (0.32 mg/kg, IV) from saline. The midazolam generalization gradient determined after the baboons were permitted to self-administer midazolam (IV) was shifted to the left of that determined before self-administration. In contrast, the midazolam generalization gradient determined after the same doses of midazolam were delivered response-independently, but in the same order and with the same temporal pattern as during self-administration, was shifted to the right of that determined just before the response-independent phase. These data suggest that sensitivity to the discriminative-stimulus effects of a drug can be modulated by behavioral experience with that drug.