title: Improved Stress Control in Serotonin Transporter Knockout Rats: Involvement of the Prefrontal Cortex and Dorsal Raphe Nucleus.
abstract: Variations in serotonin transporter (5-HTT) expression have been associated with altered sensitivity to stress. Since controllability is known to alter the impact of a stressor through differential activation of the medial prefrontal cortex (mPFC) and dorsal raphe nucleus (DRN), and that these regions are functionally affected by genetic 5-HTT down-regulation, we hypothesized that 5-HTT expression modulates the effect of controllability on stressor impact and coping. Here, we investigated the effects of a signaled stress controllability task or a yoked uncontrollable stressor on behavioral responding and mPFC and DRN activation. 5-HTT(-/-) rats proved better capable of acquiring the active avoidance task than 5-HTT(+/+) animals. Controllability determined DRN activation in 5-HTT(+/+), but not 5-HTT(-/-), rats, whereas controllability-related activation of the mPFC was independent of genotype. These findings suggest that serotonergic activation in the DRN is involved in stress coping in a 5-HTT expression dependent manner, whereas mPFC activation seems to be implicated in control over stress independently of 5-HTT expression. We speculate that alterations in serotonergic feedback in the DRN might be a potential mechanism driving this differential stress coping.
authors.affiliation: †Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, and ‡Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Anatomy, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Pieter
authors.initials: P
authors.lastname: Schipper
authors.affiliation: †Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, and ‡Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Anatomy, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Dora
authors.initials: D
authors.lastname: Lopresto
authors.affiliation: †Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, and ‡Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Anatomy, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Roy J
authors.initials: RJ
authors.lastname: Reintjes
authors.affiliation: †Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, and ‡Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Anatomy, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Joosten
authors.affiliation: †Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, and ‡Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Anatomy, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Marloes J A G
authors.initials: MJ
authors.lastname: Henckens
authors.affiliation: †Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, and ‡Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Anatomy, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Tamas
authors.initials: T
authors.lastname: Kozicz
authors.affiliation: †Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Cognitive Neuroscience, and ‡Donders Institute for Brain, Cognition and Behaviour, Centre for Neuroscience, Department of Anatomy, Radboud University Medical Centre, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Judith R
authors.initials: JR
authors.lastname: Homberg
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000502:physiology; D004195:Disease Models, Animal; D065847:Dorsal Raphe Nucleus / Q000378:metabolism* / Q000473:pathology; D004597:Electroshock; D055786:Gene Knockout Techniques; D007150:Immunohistochemistry; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000378:metabolism* / Q000473:pathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D055647:Rats, Transgenic; D017208:Rats, Wistar; D059326:Serotonergic Neurons / Q000378:metabolism* / Q000473:pathology; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism* / Q000473:pathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D050486:Serotonin Plasma Membrane Transport Proteins; C493232:Slc6a4 protein, rat; D012701:Serotonin
keywords: Serotonin; avoidance; controllability; dorsal raphe nucleus; serotonin transporter; stress