title: Serotonergic enhancement of circadian responses to light: role of the raphe and intergeniculate leaflet.
abstract: Light serves as the primary stimulus that synchronizes the circadian clock in the suprachiasmatic nucleus (SCN) to the external day/night cycle. Appropriately timed light exposure can reset the phase of the circadian clock. Some serotonergic drugs that bind to the serotonin 1A receptor can enhance phase shifts to light. The mechanism by which this potentiation occurs is not well understood. In this study, we examined where one of these drugs, 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione dihydrochloride (BMY7378), might be working in the hamster brain. Systemic (5 mg/kg), intra-dorsal raphe and intra-median raphe (both 15.6 nmol in 0.5 μL), but not intra-SCN (7.8 nmol or 15.6 nmol in 0.5 μL) injections of BMY7378 significantly potentiated phase shifts to light. Potentiation of photic shifts persisted when serotonergic innervation of the SCN was lesioned with infusions of the serotonin neurotoxin 5,7-dihydroxytryptamine into the SCN. Light-induced c-Fos expression in the rostral and caudal intergeniculate leaflet (IGL) was attenuated with systemic BMY7378, suggesting that the IGL may be involved in this response. Both complete IGL lesions and depletion of serotonergic innervation of the IGL prevented systemic BMY7378 from potentiating photic phase shifts. Together, these findings suggest that the mechanism by which BMY7378 enhances photic responses is by changing the activity of the raphe nuclei to influence how the IGL responds to light, which subsequently influences the SCN as one of its downstream targets. Identification of the network that underlies this potentiation could lead to the development of useful therapeutic interventions for treating sleep and circadian disorders.
authors.affiliation: Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada, T2N 1N4.|Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Smith
authors.affiliation: Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada, T2N 1N4.|Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1.
authors.forename: Ryan T
authors.initials: RT
authors.lastname: Jeffers
authors.affiliation: Department of Psychology, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada, T2N 1N4.|Hotchkiss Brain Institute, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1.|Department of Physiology and Pharmacology, University of Calgary, 3330 Hospital Drive NW, Calgary, AB, Canada, T2N 4N1.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Antle
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000187:drug effects; D006224:Cricetinae; D065847:Dorsal Raphe Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D005829:Geniculate Bodies / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D017440:Photoperiod; D010879:Piperazines / Q000008:administration & dosage; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D059326:Serotonergic Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D058825:Serotonin 5-HT1 Receptor Agonists / Q000008:administration & dosage; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000008:administration & dosage; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*
chemical_list: D010879:Piperazines; D058825:Serotonin 5-HT1 Receptor Agonists; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; C053428:BMY 7378
keywords: 5,7-dihydroxytryptamine; Zeitgeber; cannula; hamster; radiofrequency lesion; rodent