title: Deletion of the δ opioid receptor gene impairs place conditioning but preserves morphine reinforcement.
abstract: BACKGROUND
  Converging experimental data indicate that δ opioid receptors contribute to mediate drug reinforcement processes. Whether their contribution reflects a role in the modulation of drug reward or an implication in conditioned learning, however, has not been explored. In the present study, we investigated the impact of δ receptor gene knockout on reinforced conditioned learning under several experimental paradigms.
  
  
  METHODS
  We assessed the ability of δ receptor knockout mice to form drug-context associations with either morphine (appetitive)- or lithium (aversive)-induced Pavlovian place conditioning. We also examined the efficiency of morphine to serve as a positive reinforcer in these mice and their motivation to gain drug injections, with operant intravenous self-administration under fixed and progressive ratio schedules and at two different doses.
  
  
  RESULTS
  Mutant mice showed impaired place conditioning in both appetitive and aversive conditions, indicating disrupted context-drug association. In contrast, mutant animals displayed intact acquisition of morphine self-administration and reached breaking-points comparable to control subjects. Thus, reinforcing effects of morphine and motivation to obtain the drug were maintained.
  
  
  CONCLUSIONS
  Collectively, the data suggest that δ receptor activity is not involved in morphine reinforcement but facilitates place conditioning. This study reveals a novel aspect of δ opioid receptor function in addiction-related behaviors.
authors.affiliation: Département de Neurobiologie et Génétique, Institut de Biologie Moléculaire et Cellulaire, Illkirch, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Le Merrer
authors.forename: Ainhoa
authors.initials: A
authors.lastname: Plaza-Zabala
authors.forename: Carolina
authors.initials: C
authors.lastname: Del Boca
authors.forename: Audrey
authors.initials: A
authors.lastname: Matifas
authors.forename: Rafael
authors.initials: R
authors.lastname: Maldonado
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Kieffer
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D001522:Behavior, Animal; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects; D007859:Learning Disabilities / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D009020:Morphine / Q000008:administration & dosage*; D009042:Motivation / Q000187:drug effects; D017465:Receptors, Opioid, delta / Q000172:deficiency*; D012054:Reinforcement, Psychology; D012646:Self Administration; D013028:Space Perception / Q000187:drug effects; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D017465:Receptors, Opioid, delta; D009020:Morphine