title: Characterization of Highper, an ENU-induced mouse mutant with abnormal psychostimulant and stress responses.
abstract: BACKGROUND
  Chemical mutagenesis in the mouse is a forward genetics approach that introduces random mutations into the genome, thereby providing an opportunity to annotate gene function and characterize phenotypes that have not been previously linked to a given gene.
  
  
  OBJECTIVE
  We report on the behavioral characterization of Highper, an N-ethyl-N-nitrosourea (ENU)-induced mutant mouse line.
  
  
  METHODS
  Highper and B6 control mice were assessed for locomotor activity in the open field and home cage environments. Basal and acute restraint stress-induced corticosterone levels were measured. Mice were tested for locomotor response to cocaine (5, 20, 30, and 45 mg/kg), methylphenidate (30 mg/kg), and ethanol (0.75, 1.25, and 1.75 g/kg). The rewarding and reinforcing effects of cocaine were assessed using conditioned place preference and self-administration paradigms.
  
  
  RESULTS
  Highper mice are hyperactive during behavioral tests but show normal home cage locomotor behavior. Highper mice also exhibit a twofold increase in locomotor response to cocaine, methylphenidate, and ethanol and prolonged activation of the hypothalamic-pituitary-adrenal axis in response to acute stress. Highper mice are more sensitive to the rewarding and reinforcing effects of cocaine, although place preference in Highper mice appears to be significantly influenced by the environment in which the drug is administered.
  
  
  CONCLUSIONS
  Altogether, our findings indicate that Highper mice may provide important insights into the genetic, molecular, and biological mechanisms underlying stress and the drug reward pathway.
authors.affiliation: Department of Psychiatry, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Amy F
authors.initials: AF
authors.lastname: Eisener-Dorman
authors.forename: Janice S
authors.initials: JS
authors.lastname: Bailey
authors.forename: Laura
authors.initials: L
authors.lastname: Grabowski-Boase
authors.forename: Salvador
authors.initials: S
authors.lastname: Huitron-Resendiz
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Roberts
authors.forename: Tim
authors.initials: T
authors.lastname: Wiltshire
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Tarantino
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003345:Corticosterone / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005038:Ethylnitrosourea / Q000633:toxicity; D005260:Female; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D051379:Mice; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects; D016296:Mutagenesis; D010913:Pituitary-Adrenal System / Q000378:metabolism; D012149:Restraint, Physical; D012201:Reward; D012646:Self Administration; D013045:Species Specificity; D013312:Stress, Physiological / Q000235:genetics / Q000502:physiology
chemical_list: D008774:Methylphenidate; D000431:Ethanol; D003042:Cocaine; D005038:Ethylnitrosourea; D003345:Corticosterone