title: Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption.
abstract: BACKGROUND
  Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption.
  
  
  OBJECTIVE
  Studies were performed to determine whether selective breeding could be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA.
  
  
  METHODS
  Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA.
  
  
  RESULTS
  Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood.
  
  
  CONCLUSIONS
  Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption. Genetic factors leading to greater MA-induced sensitization may serve a protective role against high levels of MA consumption.
authors.affiliation: Department of Behavioral Neuroscience and Methamphetamine Abuse Research Center, Oregon Health & Science University, and Veterans Affairs Medical Center, Portland, OR 97239, USA.
authors.forename: Angela C
authors.initials: AC
authors.lastname: Scibelli
authors.forename: Carrie S
authors.initials: CS
authors.lastname: McKinnon
authors.forename: Cheryl
authors.initials: C
authors.lastname: Reed
authors.forename: Sue
authors.initials: S
authors.lastname: Burkhart-Kasch
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Harue
authors.initials: H
authors.lastname: Baba
authors.forename: Jeanna M
authors.initials: JM
authors.lastname: Wheeler
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Phillips
mesh_terms: D019969:Amphetamine-Related Disorders / Q000235:genetics*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001947:Breeding / Q000379:methods*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D012641:Selection, Genetic; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine