title: Sexually dimorphic dopaminergic dysfunction in a transgenic mouse model of Huntington's disease.
abstract: BACKGROUND
  Using the R6/1 transgenic mouse model of Huntington's disease (HD), we have recently shown that acute administration with the dopamine-norepinephrine reuptake inhibitor bupropion was able to rescue depressive-like behaviours in female HD mice at 12weeks of age.
  
  
  OBJECTIVE
  In this present study, we aimed to further investigate the dopamine system as well as specifically measure dopamine transporter (DAT) and D1 receptor function in female versus male R6/1 HD mice at a very early stage of the disease.
  
  
  METHODS
  We assessed the effects of acute administration of bupropion and the dopamine D1 receptor agonist SKF-8129 on spontaneous locomotor activity in 8-week-old HD and wild-type (WT) mice. We also measured dopamine levels in striatum via high performance liquid chromatography (HPLC).
  
  
  RESULTS
  We found that female (but not male) HD mice were hyposensitive to bupropion when compared to WT littermates. However, both female and male HD mice were less sensitive to SKF-81297 locomotor effects. We also found that striatal dopamine levels and dopamine turnover were reduced in HD animals, regardless of sex.
  
  
  CONCLUSIONS
  Our present findings suggest that whereas only female HD mice exhibit an impaired response to bupropion, dopamine D1 receptor function is altered in both female and male HD animals. These data are the first in vivo evidence of impaired dopamine D1 receptor-dependent function in pre-motor symptomatic HD mice suggesting that this is a candidate target for early therapeutic interventions.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia. Electronic address: thibault.renoir@unimelb.edu.au.
authors.forename: Thibault
authors.initials: T
authors.lastname: Renoir
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia.
authors.forename: Andrew
authors.initials: A
authors.lastname: Argyropoulos
authors.affiliation: Inserm UMR S894, F-75013 Paris, France; UPMC, University of Paris 06, UMR S894, F-75013 Paris, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Chevarin
authors.affiliation: Inserm UMR S894, F-75013 Paris, France; UPMC, University of Paris 06, UMR S894, F-75013 Paris, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lanfumey
authors.affiliation: Florey Institute of Neuroscience and Mental Health, Melbourne Brain Centre, University of Melbourne, Parkville, Australia; Department of Anatomy and Cell Biology, University of Melbourne, Parkville, Australia.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hannan
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D006816:Huntington Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012727:Sex Characteristics
chemical_list: D018765:Dopamine Uptake Inhibitors; D017447:Receptors, Dopamine D1; D015102:3,4-Dihydroxyphenylacetic Acid; D004298:Dopamine
keywords: Bupropion; Dopamine; Huntington's disease; Locomotor activity; Sex differences; Tandem repeat disorder