Response of the Mouse Circadian System to Serotonin 1A/2/7 Agonists in vivo: Surprisingly Little

Antle, Michael C.; Ogilvie, Malcolm D.; Pickard, Gary E.; Mistlberger, Ralph E.

doi:10.1177/0748730403251805

Cited by 75 publications

(49 citation statements)

References 67 publications

(85 reference statements)

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“…Electrical stimulation of the median raphe phase shifts circadian activity rhythms in a non-photic pattern, producing the most significant phase changes during the day, and smaller phase delays during the night (MeyerBernstein and Morin 1999). This is similar to the effect of systemic injections of serotonin agonists in hamsters (Bobrzynska et al 1996) or mice (Horikawa and Shibata 2004; but see Antle et al 2003). The rhythm in firing rate in vitro can also be reset by serotonin agonists in a dose-dependent manner in hamster, rat and mouse (Biello and Dafters 2001;Prosser 2001Prosser , 2003.…”

supporting

confidence: 55%

Circadian clock resetting in the mouse changes with age

Biello

2009

AGE

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The most widely recognised consequence of normal age-related changes in biological timing is the sleep disruption that appears in old age and diminishes the quality of life. These sleep disorders are part of the normal ageing process and consist primarily of increased amounts of wakefulness and reduced amounts of deep sleep. Changes in the amplitude and timing of the sleep-wake cycle appear to represent, at least in part, a loss of effective circadian regulation of sleep. Understanding alterations in the characteristics of stimuli that help to consolidate internal rhythms will lead to recommendations to improve synchronisation in old age. Converging evidence from both human and animal studies indicate that senescence is associated with alterations in the neural structure thought to be primarily responsible for the generation of the circadian oscillation, the suprachiasmatic nuclei (SCN). Work has shown that there are changes in the anatomy, physiology and ability of the clock to reset in response to stimuli with age. Therefore it is possible that at least some of the observed age-related changes in sleep and circadian timing could be mediated at the level of the SCN. The SCN contain a circadian clock whose activity can be recorded in vitro for several days. We have tested the response of the circadian clock to a number of neurochemicals that reset the clock in a manner similar to light, including glutamate, N-methyl-D-aspartate (NMDA), gastrin-releasing peptide (GRP) and histamine (HA). In addition, we have also tested agents which phase shift in a pattern similar to behavioural 'non-photic' signals, including neuropeptide Y (NPY), serotonin (5HT) and gamma-aminobutyric acid (GABA). These were tested on the circadian clock in young and older mice (approximately 4 and 15 months old). We found deficits in the response to specific neurochemicals but not to others in our older mice. These results indicate that some changes seen in the responsiveness of the circadian clock to light with age may be mediated at the level of the SCN. Further, the responsiveness of the circadian clock with age is attenuated to some, but not all stimuli. This suggests that not all clock stimuli loose their effectiveness with age, and that it may be possible to compensate for deficits in clock performance by enhancing the strength of those stimulus pathways which are intact.

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supporting

confidence: 55%

Circadian clock resetting in the mouse changes with age

Biello

2009

AGE

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“…While the change in phase angle of entrainment is consistent with a change in free-running period, we cannot exclude the possibility that methylphenidate may alter phase angle of entrainment by altering circadian responses to light either by altering monoamine tone in the SCN or by altering activity levels. Both monoamines and activity have been shown to attenuate phase shifts to light (Antle et al, 2003;Mistlberger and Antle, 1998;Rea and Pickard, 2000). The observation that phase angle required over a week to return to baseline after the end of methylphenidate indicates that the phase of the circadian clock was delayed.…”

Section: Discussionmentioning

confidence: 99%

Methylphenidate Modifies the Motion of the Circadian Clock

Antle

Diepen

Deboer

et al. 2012

Neuropsychopharmacol

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People with attention-deficit/hyperactivity disorder (ADHD) often experience sleep problems, and these are frequently exacerbated by the methylphenidate they take to manage their ADHD symptoms. Many of the changes to sleep are consistent with a change in the underlying circadian clock. The present study was designed to determine if methylphenidate alone could alter properties of the circadian clock. Young male mice were examined in light-dark cycles and in constant darkness and recordings were performed on behavioral activity, sleep, and electrical activity in the suprachiasmatic nucleus (SCN) of freely moving mice. Methylphenidate in the drinking water (0.08%) significantly increased activity in the mid-to-late night, and led to a delay in the onset of activity and sleep relative to the light-dark cycle. While locomotor levels returned to baseline after treatment ended, the phase angle of entrainment required at least a week to return to baseline levels. In constant darkness, the free-running period of both wheel-running and general locomotor rhythms was lengthened by methylphenidate. When the treatment ended, the free-running period either remained stable or only partially reverted to baseline levels. Methylphenidate also altered the electrical firing rate rhythms in the SCN. It induced a delay in the trough of the rhythm, an increment in rhythm amplitude, and a reduction in rhythm variability. These observations suggest that methylphenidate alters the underlying circadian clock. The observed changes are consistent with clock alterations that would promote sleep-onset insomnia.

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“…In mice there is only one report of non-photic phase shifts, and these shifts were small, averaging only about 40 min [10]. Furthermore, in vivo, 8-OH-DPAT produces non-photic phase shifts in hamsters [18] but not mice [3].…”

mentioning

confidence: 92%

The role of Period1 in non-photic resetting of the hamster circadian pacemaker in the suprachiasmatic nucleus

Hamada

Antle

Silver

2004

Neuroscience Letters

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Non-photic stimuli, such as diurnal wheel running in rodents, phase shift the circadian clock and suppress the expression of Per1 in the suprachiasmatic nucleus (SCN). The goal of the present study was to directly decrease Per1 expression using antisense (AS) oligodeoxynucleotides to determine if such suppression produced non-photic phase shifts. Injections of Per1-AS suppressed expression of Per1 within the SCN and produced phase shifts similar to those resulting from other non-photic manipulation, with large phase advances to injections during the subjective day. These results indicate that the decrease in expression of Per1 is a cause rather than a consequence of non-photic phase shifts. KeywordsAntisense oligonucleotides; In situ hybridization; Phase shift Two classes of zeitgebers can reset the mammalian circadian system: photic and non-photic [17]. Photic resetting results from retinal illumination during the night, and is mediated by glutamate release from the retino-hypothalamic tract [14] at the suprachiasmatic nucleus (SCN), the site of the mammalian circadian pacemaker. This results in the rapid expression of the Period genes Per1 and Per2 in the SCN core [8]. Non-photic resetting of the circadian clock differs importantly from photic resetting. Non-photic shifts result from arousal [2] or activity [15] during periods of quiescence in nocturnal animals. Small phase delays are observed to late night non-photic pulses, while large phase advances are observed to daytime pulses [4]. The neurotransmitters neuropeptide Y (NPY) and serotonin (5-HT) have been implicated in non-photic resetting of the circadian system [15].Expression of Per1 and Per2 in the SCN decreases following non-photic manipulations [6,9,12,13,20]. It has been suggested that light and activity "have convergent but opposite effects: light elevates Per and non-photic events decrease Per" (p. 29, Ref. [11]). It has yet to be determined if this non-photic effect on Per expression is the cause or a consequence of

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Response of the Mouse Circadian System to Serotonin 1A/2/7 Agonists in vivo: Surprisingly Little

Cited by 75 publications

References 67 publications

Circadian clock resetting in the mouse changes with age

Circadian clock resetting in the mouse changes with age

Methylphenidate Modifies the Motion of the Circadian Clock

The role of Period1 in non-photic resetting of the hamster circadian pacemaker in the suprachiasmatic nucleus

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