Effects of lighting condition on circadian behavior in 5-HT1A receptor knockout mice

Smith, Victoria M.; Jeffers, Ryan T.; McAllister, Brendan B.; Basu, Priyoneel; Dyck, Richard H.; Antle, Michael C.

doi:10.1016/j.physbeh.2014.11.005

Cited by 12 publications

(11 citation statements)

References 65 publications

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“…Serotonin and the 5‐HT 1A and 5‐HT 7 receptors have also been implicated in non‐photic phase shifting to exercise and arousal manipulations (Mistlberger et al ., ; Antle et al ., ; Gardani & Biello, ; Smith et al ., , ; Yamakawa & Antle, ), however some studies have questioned this (Antle et al ., , ; Meyer‐Bernstein & Morin, ). While numerous studies have reported non‐photic phase shifts to administration of the 5‐HT 1A/7 agonist 8‐OH‐DPAT (Tominaga et al ., ; Mintz et al ., ; Antle et al ., ), the site of action of this drug has debated.…”

Section: Discussionmentioning

confidence: 99%

“…In both mice and hamsters, responses to light are generally inhibited by 5‐HT agonists (Glass et al ., ; Rea et al ., ; Pickard et al ., , ; Pickard & Rea, ; Weber et al ., ; Rea & Pickard, ; Antle et al ., ; Smith et al ., ; Basu et al ., ) and are enhanced by 5‐HT antagonists (Moriya et al ., ; Byku & Gannon, ; Gannon, , ; Smart & Biello, ; Takahashi et al ., ; Gannon & Millan, ; Lall & Harrington, ; Kessler et al ., ; Sterniczuk et al ., ; Lungwitz & Gannon, ; Smith et al ., ). Of the various 5‐HT receptor subtypes, the 5‐HT 1A , 5‐HT 1B and 5‐HT 7 receptors seem to be important in modulating photic responses (Rea & Pickard, ; Smith et al ., , ). 5‐HT 1A agonists inhibit photic phase shifts in a dose‐dependent manner when injected systemically or directly into the SCN (Rea et al ., ; Weber et al ., ; Antle et al ., ).…”

Section: Introductionmentioning

confidence: 99%

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Chronic BMY7378 treatment alters behavioral circadian rhythms

Shankara

Orr

Mychasiuk

et al. 2017

Eur J of Neuroscience

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The mammalian circadian clock is synchronized to the day : night cycle by light. Serotonin modulates the circadian effects of light, with agonists inhibiting response to light and antagonists enhancing responses to light. A special class of serotonergic compounds, the mixed 5-HT agonist/antagonists, potentiates light-induced phase advances by up to 400% when administered acutely. In this study, we examine the effects of one of these mixed 5-HT agonist/antagonists, BMY7378, when administered chronically. Thirty adult male hamsters were administered either vehicle or BMY7378 via surgically implanted osmotic mini pumps over a period of 28 days. In a light : dark cycle, chronic BMY7378 advanced the phase angle of entrainment, prolonged the duration of the active phase and attenuated the amplitude of the wheel-running rhythm during the early night. In constant darkness, chronic treatment with BMY7378 significantly attenuated light-induced phase advances, but had no significant effect on light-induced phase delays. Non-photic phase shifts to daytime administration of a 5-HT agonist were also attenuated by chronic BMY7378 treatment. qRT-PCR analysis revealed that chronic BMY7378 treatment upregulated mRNA for 5-HT and 5-HT receptors in the hypothalamus and downregulated mRNA for 5-HT and monoamine oxidase-A in the brainstem. These results highlight adaptive changes of serotonin receptors in the brain to chronic treatment with BMY7378 and link such up- and downregulation to changes in important circadian parameters. Such long-term changes to the circadian system should be considered when patients are treated chronically with drugs that alter serotonergic function.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chronic BMY7378 treatment alters behavioral circadian rhythms

Shankara

Orr

Mychasiuk

et al. 2017

Eur J of Neuroscience

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“…The IGL is innervated by the DRN (Meyer-Bernstein & Morin, 1996), whereas the SCN receives input from both the MRN and DRN (Yamakawa & Antle, 2010). At the SCN, 5-HT regulates responses to light (Mistlberger & Antle, 1998;Rea & Pickard, 2000;Antle et al, 2003), in part through the 5-HT 1A receptor (Smith et al, 2008(Smith et al, , 2015a. Stimulation of the MRN leads to release of 5-HT at the SCN (Dudley et al, 1999), whereas stimulation of the DRN leads to 5-HT release at both the IGL and SCN (Dudley et al, 1999;Glass et al, 2000;Grossman et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Serotonergic enhancement of circadian responses to light: role of the raphe and intergeniculate leaflet

Smith

Jeffers

Antle

2015

Eur J of Neuroscience

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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.

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“…Circadian rhythmicity is essential for the control of energy metabolism, cycle-wake, hormone production and cognitive performance (Versteeg, Serlie, Kalsbeek, & Fleur, 2015;Wang, et al 2016;Zouabi et al 2016). The circadian rhythm is regulated by various brain regions, particularly mediated through 5-HT, which can be evidenced by the large number of 5-HT receptors such as the types 1A, 1B, 2A, 2C, 5A and 7 subtypes in SCN (Smith et al 2015). Therefore, in different animal models, healthy volunteers and in patients with circadian dysfunctions, it is remarkable the importance of serotonergic neuromodulation in the maintenance of endogenous rhythms, and also in understanding how circadian dysfunction can influence the efficacy and function of the serotonergic neurotransmission (Matsumura et al 2015;Holst, Valomon, & Landolt, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…In this context, 5-HT is an important regulator of circadian rhythm, by modulating responses to photic and non-photic zeitgebers (Smith et al 2015;Versteeg, Serlie, Kalsbeek, & Fleur, 2015). As with the serotonergic system of the brain, deregulation of the circadian system is associated with a range of disturbance of behavior and development, including depression, bipolar disorder, autism and disorders of the sleep-wake cycle Cho et al 2016;Schaufler et al 2016).…”

Section: Introductionmentioning

confidence: 99%