title: Effects of contextual or olfactory cues previously paired with morphine withdrawal on behavior and pain sensitivity in the rat.
abstract: BACKGROUND
  Pavlovian conditioning processes have been accorded an important role in maintaining persistent opiate administration. At least one locus for this contribution is during opiate withdrawal. These experiments studied the contribution of Pavlovian conditioning processes to morphine withdrawal.
  
  
  OBJECTIVE
  To determine whether exposure to a distinctive context or odor paired with morphine withdrawal would provoke a withdrawal syndrome, defensive behaviors (e.g., freezing) and pain modulatory (e.g., hypoalgesia) responses similar 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 experiments to study the effects on defensive behavior and pain sensitivity of naloxone-precipitated morphine withdrawal or exposure to a distinctive context or odor previously paired with such withdrawal.
  
  
  RESULTS
  Injection of 2.5 mg/kg naloxone in morphine-dependent rats precipitated a withdrawal syndrome characterized by whole body shaking, diarrhea, ptosis, and postural abnormalities (experiment 1). Exposure to either a distinctive context (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 representation accounts of Pavlovian conditioning.
authors.affiliation: Mental Health Research Institute, University of Michigan, Ann Arbor, MI 48109, USA. G.McNally@unsw.edu.au
authors.forename: G P
authors.initials: GP
authors.lastname: McNally
authors.forename: H
authors.initials: H
authors.lastname: Akil
mesh_terms: D000701:Analgesics, Opioid / Q000009:adverse effects*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003463:Cues; D005239:Fear / Q000187:drug effects / Q000502:physiology / Q000523:psychology; D008297:Male; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009812:Odorants; D009833:Olfactory Pathways / Q000187:drug effects / Q000502:physiology; D010147:Pain Measurement / Q000187:drug effects / Q000523:psychology; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology / Q000523:psychology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D009270:Naloxone; D009020:Morphine