title: Dissociation of heroin-induced emotional dysfunction from psychomotor activation and physical dependence among inbred mouse strains.
abstract: BACKGROUND
  Opiate addiction is a brain disorder emerging through repeated intoxication and withdrawal episodes. Epidemiological studies also indicate that chronic exposure to opiates may lead in susceptible individuals to the emergence of depressive symptoms, strongly contributing to the severity and chronicity of addiction. We recently established a mouse model of heroin abstinence, characterized by the development of depressive-like behaviors following chronic heroin exposure.
  
  
  OBJECTIVE
  While genetic factors regulating immediate behavioral responses to opiates have been largely investigated, little is known about their contribution to long-term emotional regulation during abstinence. Here, we compared locomotor stimulation and physical dependence induced by heroin exposure, as well as emotional dysfunction following abstinence, across mice strains with distinct genetic backgrounds.
  
  
  METHODS
  Mice from three inbred strains (C57BL/6J, Balb/cByJ, and 129S2/SvPas) were exposed to an escalating chronic heroin regimen (10-50 mg/kg). Independent cohorts were used to assess drug-induced locomotor activity during chronic treatment, naloxone-precipitated withdrawal at the end of chronic treatment, and emotional-like responses after a 4-week abstinence period.
  
  
  RESULTS
  Distinct behavioral profiles were observed across strains during heroin treatment, with no physical dependence and low locomotor stimulation in 129S2/SvPas. In addition, different behavioral impairments developed during abstinence across the three strains, with increased despair-like behavior in 129S2/SvPas and Balb/cByJ, and low sociability in 129S2/SvPas and C57BL/6J.
  
  
  CONCLUSIONS
  Our results indicate that depressive-like behaviors emerge during heroin abstinence, whatever the severity of immediate behavioral responses to the drug. In addition, inbred mouse strains will allow studying several aspects of mood-related deficits associated with addiction.
authors.affiliation: Translational Medicine and Neurogenetics, Institut de Génétique et de Biologie Moléculaire et Cellulaire, INSERM U-964, CNRS UMR-7104, Université de Strasbourg, Illkirch, 67404, France.
authors.forename: G
authors.initials: G
authors.lastname: Ayranci
authors.forename: K
authors.initials: K
authors.lastname: Befort
authors.forename: L
authors.initials: L
authors.lastname: Lalanne
authors.forename: B L
authors.initials: BL
authors.lastname: Kieffer
authors.forename: P-E
authors.initials: PE
authors.lastname: Lutz
mesh_terms: D000818:Animals; D001143:Arousal / Q000187:drug effects* / Q000235:genetics*; D004644:Emotions / Q000187:drug effects*; D003932:Heroin / Q000494:pharmacology* / Q000633:toxicity; D006556:Heroin Dependence / Q000235:genetics* / Q000523:psychology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics*; D009270:Naloxone / Q000494:pharmacology; D012919:Social Behavior; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000523:psychology
chemical_list: D009270:Naloxone; D003932:Heroin