1. The serotonergic anxiolytic buspirone attenuates circadian responses to light
- Author
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Victoria M. Smith, Ryan T. Jeffers, Sanjay Achal, Michael C. Antle, and Stephanie Iannattone
- Subjects
Male ,Agonist ,medicine.medical_specialty ,Light ,medicine.drug_class ,Chronobiotic ,Motor Activity ,Pharmacology ,Serotonergic ,CREB ,Partial agonist ,Anxiolytic ,Buspirone ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Circadian rhythm ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,030304 developmental biology ,Mice, Knockout ,8-Hydroxy-2-(di-n-propylamino)tetralin ,0303 health sciences ,Mesocricetus ,biology ,Chemistry ,General Neuroscience ,CREB-Binding Protein ,Circadian Rhythm ,Serotonin Receptor Agonists ,3. Good health ,Endocrinology ,Anti-Anxiety Agents ,Receptor, Serotonin, 5-HT1A ,biology.protein ,Suprachiasmatic Nucleus ,Proto-Oncogene Proteins c-fos ,030217 neurology & neurosurgery ,medicine.drug - Abstract
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.
- Published
- 2014