Previous assessments of associative nicotine tolerance may have confounded associative effects with novelty-induced stress effects, instrumental learning effects, or both. That is, subjects were tested in novel environments, allowed to practice the test response, or both during the tolerance development phase. In the first study, 32 male Sprague-Dawley rats were injected with various doses of nicotine and tested for nociception in the tail-flick and hot-plate tests to assess nicotine's analgesic effects. In the second study, 35 rats received nicotine explicitly paired or unpaired with a distinctive test context. All animals were equally preexposed to the test environment, and none had the opportunity to practice the test response. Paired rats developed greater nicotine tolerance than unpaired rats. This context-dependent (associative) tolerance effect was found with both tail-flick and hot-plate tests.Drug tolerance is a decrease in the effects of a drug dose following repeated drug administrations. Drug tolerance is central to the definition of drug dependence (American Psychiatric Association, 1994), and several theorists assign tolerance, or the mechanisms that produce tolerance, an important role in the genesis and maintenance of addictive behaviors (see Ramsay & Woods, 1997;Trujillo & Akil. 1995). For example, smokers may smoke more to compensate for the development of tolerance of the reinforcing effects of nicotine. Likewise, tolerance of the ill effects of nicotine may increase tobacco consumption by allowing smokers to smoke more without feeling sick (Alexander & Hadaway, 1982;Pomerleau, 1995;Trujillo & Akil). Thus, nicotine tolerance can be a symptom of physical dependence on nicotine (American Psychiatric Association, 1994) and a contributor to the severity of the smoker's physical and psychological dependence (Pomerleau).There is considerable evidence that many examples of drug tolerance represent the operation of classical conditioning (Young & Goudie, 1994), and some theorists have proposed that "learning is the primary underlying cause" (Ramsay & Woods, 1997, p. 170) of all drug tolerance phenomena. Most of the support for the role of classical conditioning in the development of drug tolerance comes from investigations of tolerance to the analgesic effects of morphine. In associative tolerance studies, animals receiving morphine explicitly paired with a distinctive test context

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