title: Developmental effects of serotonin 1A autoreceptors on anxiety and social behavior.
abstract: The serotonin 1A receptor (5-HT1A) has a major role in modulating the effects of serotonin on mood and behavior. Previous studies have shown that knockout of 5-HT1A selectively in the raphe leads to higher levels of anxiety during adulthood. However, it remains unclear whether this phenotype is due to variation in receptor levels specifically during development or throughout life. To test the hypothesis that developmental sensitivity may underlie the effects of 5-HT1A on anxiety, we used an inducible transgenic system to selectively suppress 5-HT1A levels in serotonergic raphe neurons from post-natal days (P) 14 to P30, with a maximal reduction of 40% at P21 and return to regular levels by P30. This developmental decrease in receptor levels has long-lasting consequences, increasing anxiety and decreasing social investigation in adulthood. In addition, post-natal knockdown of autoreceptors leads to long-term increases in the excitability of serotonergic neurons, which may represent a mechanism underlying the effects of post-natal receptor variation on behavior later in life. Finally, we also examined the interplay between receptor variation and juvenile exposure to stress (applied from P14 to P21). Similar to receptor knockdown, juvenile exposure to stress led to increased anxiety phenotypes but did not exacerbate 5-HT1A knockdown-mediated anxiety levels. This work indicates that the effects of 5-HT1A autoreceptors on anxiety and social behaviors are developmentally mediated and suggests that natural variations in the expression of 5-HT1A may act during development to influence individual anxiety levels and contribute to susceptibility to anxiety disorders.
authors.affiliation: 1] Departments of Neuroscience and Psychiatry, Columbia University, New York, NY, USA [2] Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Zoe R
authors.initials: ZR
authors.lastname: Donaldson
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia Research Institute and University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Piel
authors.affiliation: Department of Neuroscience, Barnard College, New York, NY, USA.
authors.forename: Tabia L
authors.initials: TL
authors.lastname: Santos
authors.affiliation: 1] Departments of Neuroscience and Psychiatry, Columbia University, New York, NY, USA [2] Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.
authors.forename: Jesse
authors.initials: J
authors.lastname: Richardson-Jones
authors.affiliation: 1] Departments of Neuroscience and Psychiatry, Columbia University, New York, NY, USA [2] Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.
authors.forename: E David
authors.initials: ED
authors.lastname: Leonardo
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia Research Institute and University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Sheryl G
authors.initials: SG
authors.lastname: Beck
authors.affiliation: Department of Psychology, Columbia University, New York, NY, USA.
authors.forename: Frances A
authors.initials: FA
authors.lastname: Champagne
authors.affiliation: 1] Departments of Neuroscience and Psychiatry, Columbia University, New York, NY, USA [2] Division of Integrative Neuroscience, The New York State Psychiatric Institute, New York, NY, USA.
authors.forename: René
authors.initials: R
authors.lastname: Hen
mesh_terms: D000367:Age Factors; D000818:Animals; D001008:Anxiety Disorders / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology; D017660:Autoreceptors / Q000172:deficiency* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D044282:Receptor, Serotonin, 5-HT1A / Q000172:deficiency* / Q000235:genetics; D012919:Social Behavior
chemical_list: D017660:Autoreceptors; D044282:Receptor, Serotonin, 5-HT1A
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