Selective breeding for divergence in novelty-seeking traits: heritability and enrichment in spontaneous anxiety-related behaviors

Behavior Genetics
John D H SteadHuda Akil

Abstract

Outbred Sprague-Dawley rats can be classified as high responders (HR) or low responders (LR) based on their levels of exploratory locomotion in a novel environment. While this novelty-seeking dimension was originally related to differential vulnerability to substance abuse, behavioral, neuroendocrine and gene expression studies suggest a fundamental difference in emotional reactivity between these animals. Here, we report the first study to selectively breed rats based on this novelty-seeking dimension. Response to novelty was clearly heritable, with a > 2-fold difference in behavior seen after eight generations of selection. Three tests of anxiety-like behavior consistently showed significantly greater anxiety in LR-bred rats compared to HR-bred animals, and this difference was diminished in the open field test by administration of the anxiolytic benzodiazepine drug, chlordiazepoxide. Cross-fostering revealed that responses to novelty were largely unaffected by maternal interactions, though there was an effect on anxiety-like behavior. These selected lines will enable future research on the interplay of genetic, environmental and developmental variables in controlling drug seeking behavior, stress and emotional reactivity.

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Citations

Dec 15, 2010·Nature·Shelly B FlagelHuda Akil
Jun 27, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·María-Julia García-FusterHuda Akil
Oct 2, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Shelly B FlagelHuda Akil
Jun 6, 2009·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Stella DrachevaWilliam M Byne
Jul 29, 2011·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·María Llorens-MartínJosé L Trejo
Jun 15, 2007·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Mary E CainMichael T Bardo
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Cortney A TurnerHuda Akil
Oct 2, 2013·Proceedings of the National Academy of Sciences of the United States of America·Zhifeng ZhouDavid Goldman
Nov 21, 2008·Behavioural Pharmacology·Shuangteng HeKenneth Grasing
May 11, 2012·Developmental Neuroscience·Rebecca K SimmonsSarah M Clinton
May 15, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Javier A PerezHuda Akil
Jul 30, 2014·Proceedings of the National Academy of Sciences of the United States of America·Sraboni ChaudhuryHuda Akil
Feb 13, 2013·Behavioral Neuroscience·Jennifer A CummingsJill B Becker
Oct 21, 2015·Genes, Brain, and Behavior·D BelinJ W Dalley
Jul 24, 2012·Pharmacology, Biochemistry, and Behavior·Sarah M ClintonHuda Akil
Mar 16, 2012·Biological Psychiatry·Tiffany M LoveJon-Kar Zubieta
Jan 11, 2012·Neuroscience and Biobehavioral Reviews·Colleen M NovakJames A Levine
Feb 10, 2011·Physiology & Behavior·Kristen A StedenfeldAlan F Sved
Oct 27, 2010·Behavioural Brain Research·Amber M MuehlmannDarragh P Devine
Sep 2, 2010·Physiology & Behavior·Eimeira PadillaF Gonzalez-Lima
Oct 13, 2009·Hormones and Behavior·Marilyn E Carroll, Justin J Anker
Jan 13, 2009·Drug and Alcohol Dependence·Marilyn E CarrollJennifer L Perry
May 26, 2009·Pharmacology, Biochemistry, and Behavior·Carlos AriasNorman E Spear
Nov 19, 2008·Pharmacology, Biochemistry, and Behavior·Cortney A TurnerHuda Akil
Oct 1, 2008·Neuroscience Letters·Cortney A TurnerStanley J Watson
Jul 1, 2011·International Journal of Evolutionary Biology·Noémie ChervetDik Heg
Apr 22, 2008·Neuroscience and Biobehavioral Reviews·Hymie AnismanJohn D H Stead

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