Developmental effects of serotonin 1A autoreceptors on anxiety and social behavior. 2014

Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
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.

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.

UI MeSH Term Description Entries
D008297 Male Males
D008808 Mice, Inbred CBA An inbred strain of mouse that is widely used in BIOMEDICAL RESEARCH. Mice, CBA,Mouse, CBA,Mouse, Inbred CBA,CBA Mice,CBA Mice, Inbred,CBA Mouse,CBA Mouse, Inbred,Inbred CBA Mice,Inbred CBA Mouse
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000367 Age Factors Age as a constituent element or influence contributing to the production of a result. It may be applicable to the cause or the effect of a circumstance. It is used with human or animal concepts but should be differentiated from AGING, a physiological process, and TIME FACTORS which refers only to the passage of time. Age Reporting,Age Factor,Factor, Age,Factors, Age
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001008 Anxiety Disorders Persistent and disabling ANXIETY. Anxiety Neuroses,Anxiety States, Neurotic,Neuroses, Anxiety,Anxiety Disorder,Anxiety State, Neurotic,Disorder, Anxiety,Disorders, Anxiety,Neurotic Anxiety State,Neurotic Anxiety States,State, Neurotic Anxiety,States, Neurotic Anxiety
D012919 Social Behavior Any behavior caused by or affecting another individual or group usually of the same species. Sociality,Behavior, Social,Behaviors, Social,Social Behaviors
D017660 Autoreceptors Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included. Autoreceptor
D044282 Receptor, Serotonin, 5-HT1A A serotonin receptor subtype found distributed through the CENTRAL NERVOUS SYSTEM where they are involved in neuroendocrine regulation of ACTH secretion. The fact that this serotonin receptor subtype is particularly sensitive to SEROTONIN RECEPTOR AGONISTS such as BUSPIRONE suggests its role in the modulation of ANXIETY and DEPRESSION. Serotonin 1A Receptor,5-HT(1A) Receptor,5-HT1A Receptor,5-Hydroxytryptamine 1A Receptor,5-Hydroxytryptamine 1A Receptors,Receptor, 5-Hydroxytryptamine 1A,Serotonin Receptor, 5-HT1A,Serotonin, 5-HT1a Receptor,1A Receptor, 5-Hydroxytryptamine,1A Receptors, 5-Hydroxytryptamine,5 HT1A Receptor,5 Hydroxytryptamine 1A Receptor,5 Hydroxytryptamine 1A Receptors,5-HT1A Serotonin Receptor,5-HT1a Receptor Serotonin,Receptor Serotonin, 5-HT1a,Receptor, 5 Hydroxytryptamine 1A,Receptor, 5-HT1A,Receptor, 5-HT1A Serotonin,Receptor, Serotonin 1A,Receptors, 5-Hydroxytryptamine 1A,Serotonin Receptor, 5 HT1A,Serotonin, 5 HT1a Receptor

Related Publications

Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
October 2010, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
April 2011, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
May 2007, Biological psychiatry,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
May 2016, Proceedings of the National Academy of Sciences of the United States of America,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
February 2010, Genes, brain, and behavior,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
July 2019, Molecular biology and evolution,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
March 1987, Pharmacology, biochemistry, and behavior,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
October 2009, Biological psychiatry,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
October 2014, Psychopharmacology,
Zoe R Donaldson, and David A Piel, and Tabia L Santos, and Jesse Richardson-Jones, and E David Leonardo, and Sheryl G Beck, and Frances A Champagne, and René Hen
January 2015, Frontiers in behavioral neuroscience,
Copied contents to your clipboard!