title: Behavioral and pharmacological evaluation of a selectively bred mouse model of home cage hyperactivity.
abstract: Daily levels of physical activity vary greatly across individuals and are strongly influenced by genetic background. While moderate levels of physical activity are associated with improved physical and mental health, extremely high levels of physical activity are associated with behavioral disorders such as attention deficit hyperactivity disorder (ADHD). However, the genetic and neurobiological mechanisms relating hyperactivity to ADHD or other behavioral disorders remain unclear. Therefore, we conducted a selective breeding experiment for increased home cage activity starting with a highly genetically variable population of house mice and evaluated the line for correlated responses in other relevant phenotypes. Here we report results through Generation 10. Relative to the Control line, the High-Active line traveled approximately 4 times as far in the home cage (on days 5 and 6 of a 6-day test), displayed reduced body mass at maturity, reduced reproductive success, increased wheel running and open field behavior, decreased performance on the rotarod, decreased performance on the Morris water maze that was not rescued by acute administration of d-amphetamine, reduced hyperactivity from chronically administered low clinical doses of d-amphetamine, and increased numbers of new cells and neuronal activation of the dentate gyrus. Standardized phenotypic differences between the lines were compared to estimates expected from genetic drift to evaluate whether the line differences could have resulted from random effects as opposed to correlated responses to selection. Results indicated line differences in body mass and locomotor responses to low doses of amphetamine were more likely due to selection than drift. The efficacy of low doses of d-amphetamine in ameliorating hyperactivity support the High-Active line as a useful model for exploring the etiology of hyperactivity-associated comorbid behavioral disorders.
authors.affiliation: Neuroscience Program, The Beckman Institute, University of Illinois at Urbana-Champaign, 405 N Mathews Avenue, Urbana, IL, USA, pmajda2@illinois.edu.
authors.forename: Petra
authors.initials: P
authors.lastname: Majdak
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Bucko
authors.forename: Ashley L
authors.initials: AL
authors.lastname: Holloway
authors.forename: Tushar K
authors.initials: TK
authors.lastname: Bhattacharya
authors.forename: Erin K
authors.initials: EK
authors.lastname: DeYoung
authors.forename: Chessa N
authors.initials: CN
authors.lastname: Kilby
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Zombeck
authors.forename: Justin S
authors.initials: JS
authors.lastname: Rhodes
mesh_terms: D000818:Animals; D018891:Dentate Gyrus; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006948:Hyperkinesis / Q000235:genetics*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000502:physiology*
references.citation: Mamm Genome. 2008 Jun;19(6):382-9
references.pmid: 18716833
references.citation: Neuropsychopharmacology. 1996 Nov;15(5):484-90
references.pmid: 8914121
references.citation: Genes Brain Behav. 2011 Apr;10(3):345-53
references.pmid: 21223504
references.citation: CNS Drugs. 2009;23 Suppl 1:33-41
references.pmid: 19621976
references.citation: J Exp Biol. 1999 Sep;202(Pt 18):2513-20
references.pmid: 10460738
references.citation: Can J Psychiatry. 2009 Oct;54(10):651-64
references.pmid: 19835672
references.citation: J Exp Biol. 2011 Jan 15;214(Pt 2):206-29
references.pmid: 21177942
references.citation: Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):301-13
references.pmid: 18057916
references.citation: Science. 1997 Mar 28;275(5308):1940-3
references.pmid: 9072973
references.citation: Hum Hered. 2013;75(2-4):175-85
references.pmid: 24081233
references.citation: Psychopharmacology (Berl). 2001 Nov;158(2):120-31
references.pmid: 11702085
references.citation: Am J Physiol Regul Integr Comp Physiol. 2003 Feb;284(2):R433-43
references.pmid: 12529284
references.citation: Public Health Nutr. 1999 Sep;2(3A):411-8
references.pmid: 10610081
references.citation: Behav Genet. 1989 Jul;19(4):473-502
references.pmid: 2803180
references.citation: Am J Psychiatry. 2008 Oct;165(10):1345-53
references.pmid: 18628349
references.citation: Integr Comp Biol. 2005 Jun;45(3):438-55
references.pmid: 21676789
references.citation: Behav Genet. 1970 Aug-Nov;1(3):195-211
references.pmid: 5527377
references.citation: Behav Neurosci. 2003 Oct;117(5):1006-16
references.pmid: 14570550
references.citation: Behav Brain Res. 2006 Oct 2;173(1):138-47
references.pmid: 16860407
references.citation: Neuroscience. 2008 Sep 9;155(4):1048-58
references.pmid: 18664375
references.citation: Clin Psychol Rev. 2006 Aug;26(4):433-44
references.pmid: 16480802
references.citation: Psychiatr Clin North Am. 2010 Jun;33(2):357-73
references.pmid: 20385342
references.citation: Behav Genet. 2005 Sep;35(5):675-92
references.pmid: 16184494
references.citation: Psychopharmacology (Berl). 1993;112(4):503-10
references.pmid: 7871064
references.citation: Neuroscience. 2013 Feb 12;231:125-35
references.pmid: 23178911
references.citation: Biol Psychiatry. 2009 Apr 1;65(7):620-4
references.pmid: 19150052
references.citation: Physiol Behav. 2008 Feb 27;93(3):637-50
references.pmid: 18155256
references.citation: Prog Neurobiol. 2013 Sep;108:44-79
references.pmid: 23856628
references.citation: J Am Acad Child Adolesc Psychiatry. 1997 Aug;36(8):1036-45
references.pmid: 9256583
references.citation: J Abnorm Child Psychol. 2007 Dec;35(6):999-1008
references.pmid: 17690977
references.citation: Neuropharmacology. 2009 Dec;57(7-8):590-600
references.pmid: 19715710
references.citation: Genet Res. 1973 Dec;22(3):291-321
references.pmid: 4792435
references.citation: J Comp Physiol B. 2001 Nov;171(8):651-9
references.pmid: 11765974
references.citation: Proc Biol Sci. 2011 Feb 22;278(1705):574-81
references.pmid: 20810439
references.citation: CNS Drugs. 2010 Feb;24(2):99-117
references.pmid: 20088618
references.citation: Psychopharmacology (Berl). 2003 May;167(3):242-50
references.pmid: 12669177
references.citation: J Child Psychol Psychiatry. 2013 Jan;54(1):3-16
references.pmid: 22963644
references.citation: Am J Psychiatry. 2007 Apr;164(4):647-55
references.pmid: 17403979
references.citation: Behav Genet. 1998 May;28(3):227-37
references.pmid: 9670598
references.citation: Behav Genet. 2011 Jul;41(4):571-82
references.pmid: 21184167
references.citation: J Abnorm Child Psychol. 2011 Jul;39(5):623-32
references.pmid: 21494861
references.citation: Public Health Nutr. 2009 Aug;12(8):1052-60
references.pmid: 18778532
references.citation: J Exp Biol. 2013 Feb 1;216(Pt 3):515-23
references.pmid: 23325861
references.citation: Neurosci Biobehav Rev. 2001 May;25(3):235-60
references.pmid: 11378179
references.citation: Behav Brain Res. 2000 Sep;114(1-2):135-43
references.pmid: 10996054
references.citation: Neuroscience. 2010 Feb 17;165(4):1087-99
references.pmid: 19932887
references.citation: Integr Comp Biol. 2005 Jun;45(3):416-25
references.pmid: 21676787
references.citation: J Dev Behav Pediatr. 2002 Feb;23(1):16-22
references.pmid: 11889347
references.citation: J Neurosci. 2010 Aug 18;30(33):11043-56
references.pmid: 20720111
references.citation: PLoS One. 2008 Apr 09;3(4):e1974
references.pmid: 18398484
references.citation: Curr Psychiatry Rep. 2012 Oct;14(5):579-89
references.pmid: 22843546
references.citation: J Atten Disord. 2002 Jan;5(3):143-54
references.pmid: 11911007
references.citation: Alcohol Clin Exp Res. 2012 Oct;36(10):1803-10
references.pmid: 22486407
references.citation: J Child Psychol Psychiatry. 2006 Nov;47(11):1167-74
references.pmid: 17076756
references.citation: Behav Genet. 1997 Mar;27(2):145-54
references.pmid: 9145553
references.citation: Proc Natl Acad Sci U S A. 2003 Mar 4;100(5):2917-22
references.pmid: 12584362
references.citation: Int J Obes Relat Metab Disord. 2001 Jun;25(6):822-9
references.pmid: 11439296