Drug anticipation and drug addiction. The 1998 H. David Archibald Lecture

Environmental cues associated with drug use become capable of eliciting wit hdrawal symptoms, craving and relapse to drug self-administration The pheno menon, although noted almost 150 years ago, has repeatedly been confirmed i n epidemiological and experimental studies. Drug tolerance, which is closel y correlated with withdrawal symptoms and craving, is also modulated by dru g-associated environmental cues. The contribution of predrug cues to withdr awal and tolerance is emphasized in a Pavlovian conditioning analysis of dr ug administration. Drug-induced disturbances are modulated by homeostatic r esponses elicited by pharmacological stimulation. According to the conditio ning analysis, we learn to anticipate the drug effect; corrective responses (conditional compensatory responses) occur in the presence of situations a nd events that have been associated with the drug in the past. These condit ional responses, seen in anticipation of drugs, importantly contribute to d rug tolerance, failures of tolerance (enigmatic overdoses), and withdrawal symptoms. I review evidence indicating that a complete analysis of drug wit hdrawal and tolerance requires an appreciation of the contribution of Pavlo vian conditioning.