title: Conditioned rewarding effects of morphine and methadone in mice pre-exposed to cocaine.
abstract: BACKGROUND
  Methadone is widely accepted as the most effective treatment of opioid dependence. However, clinical observations indicate that the medication is less effective in individuals abusing cocaine. Diminished therapeutic efficacy of methadone in cocaine users is intriguing, but its mechanism has not been studied.
  
  
  METHODS
  Here, the conditioned place preference (CPP) procedure was used to examine the effects of the dose, number of conditioning sessions and pre-exposure to cocaine on the rewarding effects of morphine and methadone. Vehicle-pre-exposed and cocaine-sensitized mice (five injections of 10 mg/kg over 16 days) were conditioned using methadone (0, 0.1, 0.5, 3, and 5 mg/kg) or morphine (0, 1, and 10 mg/kg). Place preference was measured after one and again after two additional conditioning sessions.
  
  
  RESULTS
  As expected, morphine at 10 mg/kg produced CPP following just one conditioning session. While a single conditioning session with 1 mg/kg of morphine produced no CPP, the rewarding effect became apparent following two additional conditioning sessions as well as in mice pre-exposed to cocaine. Methadone produced CPP following one conditioning session at doses of 0.5, 3 and 5 mg/kg. However, unlike with morphine, methadone's rewarding effect was not enhanced by two additional conditioning sessions or by pre-exposure with cocaine.
  
  
  CONCLUSIONS
  Prior exposure to cocaine increases unconditioned motivational effects of morphine but not of methadone.
authors.affiliation: Behavioral Neuroscience and Drug Development, Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, PL 31-343 Kraków, Poland. nfpopik@cyf-kr.edu.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Hołuj
authors.forename: Adam
authors.initials: A
authors.lastname: Bisaga
authors.forename: Piotr
authors.initials: P
authors.lastname: Popik
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D016739:Behavior, Addictive / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008691:Methadone / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009020:Morphine / Q000494:pharmacology*; D009042:Motivation / Q000187:drug effects; D012201:Reward; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D000697:Central Nervous System Stimulants; D009020:Morphine; D003042:Cocaine; D008691:Methadone