Serotonergic serotonin1A mixed agonists/antagonists elicit large-magnitude phase shifts in hamster circadian wheel-running rhythms

Gannon, Robert L.

doi:10.1016/s0306-4522(03)00161-1

Cited by 37 publications

(32 citation statements)

References 28 publications

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“…As with the present findings, earlier reports noted that compounds acting at the 5HT1A receptor potentiate the response to light (Gannon, 2003;Gannon and Millan, 2006;Moriya et al, 1998;Rea et al 1995;Lall and Harrington, 2006). These studies, however, uniformly employed an experimental design in which animals were housed in constant darkness for several days prior to treatment.…”

Section: Discussionsupporting

confidence: 76%

“…However, sildenafil did not appear to alter the number of transient cycles following a single light pulse-induced phase shift, whereas in our experiments NAN-190 sped the rate of resetting such that fewer transient cycles occurred. The latter was observed both in the single light pulse and re-entrainment paradigms; earlier studies reported similar abrupt phase shifts with NAN-190 (Rea et al, 1995) and with BMY 7378 and S15535, compounds that also act as 5HT1A partial agonists (Gannon, 2003).…”

Section: Discussionsupporting

confidence: 59%

“…Serotonin (5HT) itself and synthetic agonists are able to phase shift the circadian rhythm during the subjective day and attenuate light-induced phase shifting during the subjective night in hamsters (Bobrzynska et al, 1996;Gannon and Millan, 2006;Horikawa et al, 2000;Rea et al, 1994;Tominaga et al, 1992). Furthermore, there have been several reports of 5HT1A antagonists potentiating the phase advance to light, suggesting that serotonergic tone on this receptor normally provides an inhibitory input to the SCN (Gannon, 2003;Gannon and Millan, 2006;Rea et al, 1995;Lall and Harrington, 2006).In this study, we investigated the properties of NAN-190 as a pharmacological treatment for circadian desynchrony. NAN-190 acts at the 5HT1A receptor, activating autoreceptors and functionally antagonizing post-synaptic receptors (Claustre et al, 1991;Ryldelek-Fitzgerald et al, 1990).…”

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confidence: 99%

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NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

2008

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Health problems can arise from de-synchrony between the external environment and the endogenous circadian rhythm, yet the circadian system is not able to quickly adjust to large, abrupt changes in the external daily cycle. In this study, we investigated the ability of to potentiate the circadian rhythm response to light as measured by phase of behavioral activity rhythms. (5 mg/kg, i.p.) was able to significantly potentiate the response to light both in dark-adapted and entrained hamsters. Furthermore, was effective even when administered up to 6 hours after light onset. Response to a light pulse was both greater in magnitude and involved fewer unstable transient cycles. Finally, was able to speed re-entrainment to a 6 h advance of the light: dark cycle by an average of 6 days when compared to vehicle-treated animals. This work suggests that compounds like NAN-190 may hold great potential as a pharmaceutical treatment for jetlag, shift work, and other circadian disorders. Keywordsserotonin; circadian; light; rhythm; jet-lag; phase shift; transient; entrainment Circadian rhythms are endogenously generated rhythms that coordinate processes such as hormone release, digestive enzyme secretion, and the sleep/wake cycle. In mammals, the major pacemaker is located in the suprachiasmatic nucleus (SCN) in the brain, which uses environmental cues to synchronize, or entrain, internal rhythms to the external surroundings (Rusak and Zucker, 1979; Ralph et al., 1990). Jetlag occurs when internal circadian rhythms become desynchronized from the external time. In humans, this desynchronization results in acute negative effects such as lowered performance levels on the job, difficulty sleeping at the appropriate times, and gastrointestinal problems. If frequent or prolonged, circadian desynchrony may be associated with more chronic health problems in people such as increased risk of breast cancer, cardiovascular disease, reproductive difficulties and peptic ulcers (Knutsson, 2003;Megdal et al., 2005). Studies using laboratory animals even link jetlag with increased rate of tumor growth and increased mortality in aged mice (Davidson et al., 2006;Filipski et al., 2004). Given the detrimental effects, studies have investigated several different methods to reduce circadian desynchrony. Melatonin, exposure to bright light, and gradual shifting of the sleep/wake cycle prior to jet travel in varying combinations have all been shown *Corresponding author. Tel: 1-413-585-3925; fax: 1-413-585-3786. E-mail address: mharring@email.smith.edu (M. Harrington). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the ...

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Section: Discussionsupporting

confidence: 76%

Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 99%

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NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

2008

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“…However, blockade of raphe-localized SERT would increase 5-HT 1A autoreceptor inhibition of raphe neuronal firing and attenuate serotonergic output from the raphe (Millan et al 2000). Consequently, light-induced phase advances of hamster circadian activity rhythms should be increased, as 5-HT input to the SCN is inhibitory (Weber et al 1998;Gannon 2003;Gannon and Millan 2006a). In addition, there is extensive SERT immunoreactivity within the SCN of hamsters and other rodents (Sur et al 1996;Amir et al 1998;Legutko and Gannon 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Accordingly, in the present study, we the influence of citalopram, fluoxetine, fluvoxamine, and paroxetine (upon light-induced phase shifts) in circadian activity rhythms in hamsters. This model was selected in view of its broad utilization in previous studies (Pickard et al 1996;Van Reeth et al 1997;Kennaway and Moyer 1998;Weber et al 1998;Gannon 2003;Sprouse et al 2005;Millan 2005, 2006b;Lall and Harrington 2006) and because altered diurnal rhythms in hamsters provoke changes in affective responses, including depressive-like behaviors (Prendergast and Nelson 2005). SSRIs were compared to venlafaxine, a mixed inhibitor of 5-HT and noradrenaline (NA) reuptake (SNRI), reboxetine, a preferential NA reuptake inhibitor, and bupropion, a preferential inhibitor of dopamine (DA) reuptake (Ascher et al 1995;Millan et al 2000;Wong et al 2000;Bymaster et al 2001;Morilak and Frazer 2004;Walter 2005;Millan 2006).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of serotonin, noradrenaline and dopamine reuptake inhibitors on light-induced phase advances in hamster circadian activity rhythms

Gannon

Millan

2007

Psychopharmacology

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These data suggest that suppression of serotonin (but not noradrenaline or dopamine) reuptake by SSRIs and SNRIs modifies circadian locomotor activity rhythms in hamsters. Further, they support the notion that an inhibitory influence upon the early-morning light-induced advance in circadian activity contributes to the therapeutic effects of serotonin uptake inhibitors in certain depressed patients.

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Air Pollution and the Nervous System: Diseases of the Brain Caused by Air Pollutants and Air Pollution

Lenzi

Bonsanto

2017

Clinical Handbook of Air Pollution-Related Diseases

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Serotonergic serotonin1A mixed agonists/antagonists elicit large-magnitude phase shifts in hamster circadian wheel-running rhythms

Cited by 37 publications

References 28 publications

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

NAN-190 potentiates the circadian response to light and speeds re-entrainment to advanced light cycles

Evaluation of serotonin, noradrenaline and dopamine reuptake inhibitors on light-induced phase advances in hamster circadian activity rhythms

Air Pollution and the Nervous System: Diseases of the Brain Caused by Air Pollutants and Air Pollution

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