Abstract Rationale: Pavlovian conditioning processes

have been accorded an important role in maintaining per-sistent opiate administration. At least one locus for this contribution is during opiate withdrawal. These experi-ments studied the contribution of Pavlovian conditioning processes to morphine withdrawal. Objectives: To deter-mine whether exposure to a distinctive context or odor paired with morphine withdrawal would provoke a with-drawal syndrome, defensive behaviors (e.g., freezing) and pain modulatory (e.g., hypoalgesia) responses simi-lar to those produced by exposure to stimuli signaling other sources of aversive stimulation (e.g., footshock), or whether both withdrawal and fear-like responses would be provoked. Methods: Rats were used in four experi-ments to study the effects on defensive behavior and pain sensitivity of naloxone-precipitated morphine with-drawal or exposure to a distinctive context or odor previ-ously paired with such withdrawal. Results: Injection of 2.5 mg/kg naloxone in morphine-dependent rats precipi-tated a withdrawal syndrome characterized by whole body shaking, diarrhea, ptosis, and postural abnormali-ties (experiment 1). Exposure to either a distinctive con-text (experiment 2) or odor (experiments 3) previously paired with morphine withdrawal provoked the species-typical defense response of freezing but not signs of withdrawal. Exposure to an odor previously paired with morphine withdrawal also provoked hypoalgesia in the formalin test, which was mediated by activity at opioid receptors (experiment 4). Conclusions: These results show that opiate withdrawal supports the conditioning of defensive and hypoalgesic responses consistent with the arousal of a fear motivational system. The emergence of fear in these experiments, and the relationship between the freezing observed here and the learned avoidance and suppression observed in other withdrawal conditioning preparations, is discussed with reference to dual repre-sentation accounts of Pavlovian conditioning