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Unformatted text preview: Drug Tolerance, Drug Addiction, and Drug Anticipation Shepard Siegel McMaster University, Hamilton, Ontario, Canada ABSTRACT Environmental cues associated with drugs of- ten 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 pres- ence 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 ap- parent that internal predrug cues, as well as environ- mental 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. Ac- cording 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. KEYWORDS addiction; drug tolerance; Pavlovian condi- tioning; withdrawal symptoms When drug-control legislation was first implemented in 1915, it became clear that drug use could not be ended simply by leg- islative fiat. Lawrence Kolb, the first superintendent of the Narcotics Treatment Farm in Lexington, Kentucky, noted that treated addicts experienced drug-withdrawal symptoms and craving, and often relapsed, when confronted with situations that had been paired with their drug use: We see this plainly ex- emplified in the cured tobacco smoker . . . A cured smoker who usually does not crave tobacco may feel an intense desire re- sembling hunger when he gazes on a box of cigars or sits in the company of friends who are smoking (Kolb, 1927, p. 39). Other researchers subsequently described examples of patients who displayed withdrawal symptoms and who craved drugs when confronted with cues that had signaled the druge.g., seeing the paraphernalia of addiction such as a syringe and tourniquet, discussing drugs with others, or even seeing actors injecting heroin in a movie. The results of many experiments with animals support clinical observations that predrug cues are powerful elicitors of withdrawal symptoms (see reviews by McDonald & Siegel, 2004; Siegel & Ramos, 2002). In summary, drug users respond in anticipation of drugs with withdrawal symptoms. The study of anticipatory responding to biologically significant effects is the study of Pavlovian condi- tioning....
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