Associative tolerance to nicotine analgesia in the rat: tail-flick and hot-plate tests.

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.