title: Chronic and intermittent morphine treatment differently regulates opioid and dopamine systems: a role in locomotor sensitization.
abstract: BACKGROUND
  Behavioral sensitization induced by repeated morphine administrations may depend on patterns of administration. However, neurobiological mechanisms involved in this sensitization are largely unknown.
  
  
  OBJECTIVE
  We compared the effects of intermittent (20 mg/kg, once daily for 7 days) and chronic (escalating doses from 5 to 40 mg/kg, three times a day for 5 days) morphine treatments in mice on locomotor activity. We also quantified, by autoradiography, mu opioid receptor (MOR) in ventral tegmental area (VTA), dopamine D1 (D1R) and D2 (D2R) receptors in striatum.
  
  
  RESULTS
  Whereas the intermittent treatment led to a long-term sensitization to locomotor effects of morphine [until withdrawal day (WD) 14], the chronic treatment induced a tolerance (WD1) followed by a transient sensitization (WD14). Binding studies demonstrated a decrease of MOR in VTA at WD1 for the chronic treatment. In contrast, striatal D1R level was decreased at WD1, and increased at WD14 for the chronic treatment. For the D2R, we observed a decrease from WD1 to WD14 for the intermittent treatment and an increase at WD1 followed by a decrease at WD14 for the chronic treatment.
  
  
  CONCLUSIONS
  These results demonstrate that chronic and intermittent morphine treatments could induce different behavioral adaptations that could be explained in part by distinct changes occurring in dopamine and opioid systems.
authors.affiliation: Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8206, Paris, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Le Marec
authors.forename: Cynthia
authors.initials: C
authors.lastname: Marie-Claire
authors.forename: Florence
authors.initials: F
authors.lastname: Noble
authors.forename: Nicolas
authors.initials: N
authors.lastname: Marie
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D008297:Male; D051379:Mice; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
chemical_list: D000701:Analgesics, Opioid; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D017450:Receptors, Opioid, mu; D009020:Morphine