title: Melatonin reduces motivation for cocaine self-administration and prevents relapse-like behavior in rats.
abstract: BACKGROUND
  Melatonin is a hormone involved in the entrainment of circadian rhythms, which appears dysregulated in drug users. Further, it has been demonstrated that melatonin can modulate the reinforcing effects of several drugs of abuse and may therefore play a role in drug addiction.
  
  
  OBJECTIVE
  Here, we investigated whether administration of melatonin reduces relapse-like behavior and the motivation to seek cocaine in rats.
  
  
  METHODS
  Male Sprague-Dawley rats were submitted to long-term cocaine self-administration training. Thereafter, melatonin effects were assessed on: (1) the motivation to work for cocaine in the break point test, (2) the relapse-like behavior in the cue-induced reinstatement test, (3) the distance traveled in the open field test, and (4) sucrose preference in a two-bottle choice paradigm. Melatonin, 25 or 50 mg/kg, was injected 3-4 h after the dark phase onset, 30 min prior to each test.
  
  
  RESULTS
  Both doses of melatonin decreased the number of active pokes in both break point and cue-induced reinstatement tests, demonstrating that melatonin can reduce the cocaine-seeking behavior and the motivation to work for cocaine. Administration of the higher dose of this hormone, however, significantly reduced the number of inactive pokes during the cue-induced reinstatement test and tended to reduce animals' locomotor activity in the open field test. Sucrose preference was unchanged in both vehicle- and melatonin-treated animal groups.
  
  
  CONCLUSIONS
  Our data suggest that melatonin administration may lower the risk of relapse triggered by cues in cocaine-experienced animals.
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.
authors.forename: Tatiane T
authors.initials: TT
authors.lastname: Takahashi
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany.
authors.forename: Valentina
authors.initials: V
authors.lastname: Vengeliene
authors.affiliation: Institute of Psychopharmacology, Central Institute of Mental Health, Faculty of Medicine Mannheim, Heidelberg University, J5, 68159, Mannheim, Germany. rainer.spanagel@zi-mannheim.de.
authors.forename: Rainer
authors.initials: R
authors.lastname: Spanagel
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000517:prevention & control* / Q000523:psychology; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012008:Recurrence; D012646:Self Administration; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D013395:Sucrose; D003042:Cocaine; D008550:Melatonin
keywords: Addiction; Clock gene theory; Melatonin receptors; Progressive ratio; Psychostimulants; Reinstatement