Basic research concerning drug tolerance and withdrawal may inform clinical practice, and vice versa. Three areas that integrate the work of the laboratory and the clinic are discussed: (a) drug overdose, (b) cue exposure treatment of addiction, and (c) pharmacological treatment of withdrawal symptoms. The areas are related in that they indicate the contribution of drug-paired cues to the effects of addictive drugs and the role of Pavlovian conditioning of drug effects in drug tolerance and withdrawal symptoms.

There is considerable evidence that drug-paired cues become associated with drug effects. It has been hypothesized that these cues act as Pavlovian conditional stimuli (CSs), and elicit conditional compensatory responses that contribute to tolerance. On the basis of a conditioning analysis of tolerance, we would expect that it should be possible to establish drug-paired cues as occasion setters, as well as conditional stimuli. Using feature-positive discrimination training, we evaluated the contribution of occasion-setting stimuli (as well as CSs) to tolerance to the hypothermic effect of ethanol in rats. The results indicated that a complete associative analysis of drug tolerance should incorporate not only the CS properties of predrug cues, but also the occasion-setting properties of such cues. The findings have implications for interpreting conflicting findings concerning extinction of tolerance and for cue-exposure treatments of addiction.

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