Drug Tolerance, Drug Addiction, and Drug Anticipation

Environmental cues associated with drugs often elicit withdrawal symptoms and relapse to drug use. Such cues also modulate drug tolerance. The contribution of drug-associated stimuli to withdrawal and tolerance is emphasized in a Pavlovian-conditioning analysis of drug administration. Conditional responses occur in the presence of cues that have been associated with the drug in the past, such as the setting in which the drug was taken. These conditional responses mediate the expression of tolerance and withdrawal symptoms. Recently, it has become apparent that internal predrug cues, as well as environmental cues, elicit pharmacological conditional responses that contribute to tolerance and withdrawal. Such internal cues include cognitive or proprioceptive cues incidental to self-administration, drug-onset cues that are experienced shortly after administration, and emotional cues. According to the conditioning analysis, addiction treatment should incorporate learning principles to extinguish the association between stimuli (environmental and internal) present at the time of drug administration and the effects of the addictive drug.