title: The serotonergic anxiolytic buspirone attenuates circadian responses to light.
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.
authors.affiliation: Department of Psychology, University of Calgary, Calgary, AB, Canada; Hotchkiss Brain Institute, University of Calgary, Calgary, AB, Canada.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Smith
authors.forename: Stephanie
authors.initials: S
authors.lastname: Iannattone
authors.forename: Sanjay
authors.initials: S
authors.lastname: Achal
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Jeffers
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
mesh_terms: D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D002065:Buspirone / Q000494:pharmacology*; D050882:CREB-Binding Protein / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008027:Light; D008297:Male; D008647:Mesocricetus; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010766:Phosphorylation / Q000187:drug effects; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011897:Random Allocation; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D016760:Proto-Oncogene Proteins c-fos; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D050882:CREB-Binding Protein; C494364:Crebbp protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D002065:Buspirone
keywords: JunB; hamster; mouse; photic phase shift