Analgesic Tolerance of Nicotine.

Nicotine also produces analgesia, therefore, looking at nicotine

analgesia, which is an easily measurable effect, enables the investigation of associative tolerance to
nicotine. Tolerance to nicotine’s analgesic effects is greater in animals that receive nicotine explicitly
paired with a specific environment than in animals that receive the same amount of nicotine and
exposure to the environment but with the environment and the nicotine explicitly unpaired (e.g.,
Cepeda-Benito et al. 1998). This contextual effect has been observed also in the development of
tolerance to other effects of nicotine, such as nicotine's anorectic effects and nicotine-induced
corticosterone (CORT) release (Caggiula et al. 1991). It has been proposed that this associative
tolerance occurs through classical conditioning that involves pairing drug administration cues with
drug effects, so that physiological mechanisms react "in expectancy" of a drug dose when presented
with drug administration cues.