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The serotonergic anxiolytic buspirone attenuates circadian responses to light.
MedLine Citation:
PMID:  25195769     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Serotonergic drugs modify circadian responses to light, with agonists attenuating and some partial agonists or antagonists potentiating photic phase shifts. The anxiolytic buspirone is a 5-HT1A receptor partial agonist. Given that buspirone is used therapeutically to manage generalised anxiety disorder, it would be useful to understand if and how this drug may modify circadian responses to light, not only to help manage side effects, but also to examine its potential use as a chronobiotic. Here we examined behavioral and molecular responses to phase-shifting light in mice and hamsters treated with buspirone. Phase advances to late subjective night light pulses in hamsters and wildtype mice were significantly attenuated by buspirone. 5-HT1A receptor knockout mice exhibited potentiated photic phase shifts when pretreated with buspirone. In wildtype mice, the attenuated phase shifts were accompanied by increased cFos expression in the suprachiasmatic nucleus, whereas potentiated phase shifts in knockouts were accompanied by increased phosphorylation of extracellular signal-regulated kinase (ERK) and cyclic AMP response element-binding protein (CREB), and decreased cFos expression. Attenuated photic phase shifts in buspirone-treated hamsters were accompanied by decreased phosphorylation of ERK and CREB. Chronic buspirone treatment decreased the amplitude of wheel-running rhythms, lengthened the duration of the active phase and advanced the phase angle of entrainment. Buspirone administration at midday produced non-photic phase advances in wildtype but not 5-HT1A receptor knockout mice. These findings suggest that buspirone affected the circadian system in a manner similar to the 5-HT1A/7 agonist (±)-8-Hydroxy-2-dipropylaminotetralin hydrobromide, primarily through the 5-HT1A receptor, and suggest that therapeutic use of buspirone to manage anxiety may impact circadian function.
Authors:
Victoria M Smith; Stephanie Iannatonne; Sanjay Achal; Ryan T Jeffers; Michael C Antle
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-6
Journal Detail:
Title:  The European journal of neuroscience     Volume:  -     ISSN:  1460-9568     ISO Abbreviation:  Eur. J. Neurosci.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-8     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8918110     Medline TA:  Eur J Neurosci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
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