Glucose enhancement of tolerance to morphine and ethanol in rats

According to a Pavlovian conditioning analysis, drug tolerance (in part) results from an association between cues present at the time of drug administration and the effect of the drug. Associations are enhanced by glucose administered after a conditioning trial, such enhancement being inversely related to the interval between the trial and glucose administration. If conditioning contributes to tolerance, glucose administered shortly after each drug administration should facilitate the acquisition of tolerance. Acquisition of tolerance was assessed both when glucose was administered shortly after each drug administration (immediate glucose) and when glucose was administered 24 h after each drug administration. As expected on the basis of the conditioning interpretation of tolerance, immediate glucose facilitated the acquisition of tolerance to the analgesic effect of morphine (Experiment 1) and the ataxic effect of ethanol (Experiment 2).