Serotonergic mediation of constant light-potentiated nonphotic phase shifting of the circadian locomotor activity rhythm in Syrian hamsters

Abstract

(1-3 days) constant light exposure (brief LL) potentiates nonphotic phase shifting induced by sleep deprivation and serotonin (5-HT) agonist stimulation. The present assessments reveal that exposure to brief LL markedly alters the magnitude and shape of the 5-HT 1A,7 receptor agonist, 8-(ϩ)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahyronapthalene (8-OH-DPAT) phase-response curve, facilitating (ϳ12 h) phase-advance shifts during the early morning when serotonergics have no phase-shifting effect. Brief LL also reduces the threshold for 8-OH-DPAT shifting at midday, evidenced by 5-to 6-h phase-advance shifts elicited by dosages that have no effect without the LL treatment. The brief LL-potentiated phase advances to intraperitoneal 8-OH-DPAT at zeitgeber time 0 (ZT 0) were blocked by the 5-HT 1A antagonists, pindolol and WAY 100635, indicating that this shifting is mediated by 5-HT 1A receptors. Antagonists with action at 5-HT7 receptors, including ritanserin and metergoline, were without effect. Although autoradiographic analyses of [ 3 H]8-OH-DPAT binding indicate that brief LL does not upregulate suprachiasmatic nucleus (SCN) 5-HT 1A receptor binding, intra-SCN microinjection of 8-OH-DPAT at ZT 0 in brief LL-exposed hamsters induced shifts similar to those produced by intraperitoneal injection, suggesting that SCN 5-HT 1A receptors mediate potentiated 8-OH-DPAT-induced shifts during the early morning. Lack of shifting by intra-SCN 8-OH-DPAT at ZT 6 or 18 (when intraperitoneal 8-OH-DPAT induces large shifts), further indicates that brief LL-potentiated shifts at these time points are mediated by 5-HT target(s) outside the SCN. Significantly, sleep deprivation-induced phase-advance shifts potentiated by brief LL (ϳ9 h) at ZT 0 were blocked by pindolol, suggesting that these behavioral shifts could be mediated by the same SCN 5-HT 1A receptor phase-resetting pathway as that activated by 8-OH-DPAT treatment. suprachiasmatic nucleus; sleep deprivation; 8-OH-DPAT THE SUPRACHIASMATIC NUCLEUS (SCN) of the anterior hypothalamus is the site of the master circadian clock in mammals (21,23,40,47). The SCN clock is entrained by photic input received principally from the retina via the retinohypothalamic tract and nonphotic signaling received from the intergeniculate leaflet via the geniculohypothalamic tract, and possibly from the midbrain raphe nuclei (28). Inputs from these nonphotic sources to the SCN are mediated by neuropeptide Y and serotonin (5-HT), respectively (34, 41).In Syrian hamsters, nonphotic stimuli, in the form of behavioral manipulations (e.g., social interaction, cage changing, novel wheel exposure, or sleep deprivation) or pharmacological intervention (e.g., 5-HT agonists or benzodiazepines) can induce phase shifts similar in magnitude to photic shifts (ϳ1-2 h) (15,31,36). Recently, we demonstrated that nonphotic shifting responses of hamsters receiving sleep deprivation treatment or systemic application of the 5-HT 1A,7 receptor agonist 8-OH-DPAT are greatly potentiated (ϳ10 -12 h) by prior treatment with s...

Chronic ethanol intake modulates photic and non-photic circadian phase responses in the Syrian hamster

“…5). Similar responses to other non-photic phase-shifting stimuli have been reported recently in animals pre-exposed to constant light for one or more cycles prior to phase-shift testing (Knoch et al, 2004(Knoch et al, , 2006Landry and Mistlberger, 2005). Thus, these responses may have been related to our decision to delay the onset of darkness from the normal ZT 12 until ZT 21 on the day of treatment in order to facilitate triazolam administration during the night phase of the LD cycle, resulting in exposure to 23 hours of continuous light.…”

“…We chose the latter strategy, both to equate lighting conditions for the ZT 6 and ZT 21 injections, and for experimental convenience. However, recent studies have shown that pre-exposure to even relatively short periods of continuous light (i.e., 1−3 circadian cycles) can dramatically potentiate the response to other varieties of non-photic stimuli (Knoch et al, 2004(Knoch et al, ,2006Landry and Mistlberger, 2005). Thus, these observations suggest that similar light-induced potentiation of non-photic phase responses may also occur for triazolam-induced responses in some animals.…”

Two Distinct Serotonin Receptors Co-mediate Non-photic Signals to the Circadian Clock

“…It has been reported that systemic administration of 8-OH-DPAT causes a large non-photic phase shift in behavioral activity by activating 5-HT 1A receptors on the SCN when exposed to short-term constant light (15). This phase-shifting is associated with the decreased 5-HT release in the SCN and is not blocked by 5-HT 7 receptor antagonists.…”

Illuminating serotonergic gateways for strong resetting of the mammalian circadian clock

“…One possibility is that 5-HT receptor numbers are altered by brief LL, such that postsynaptic responses are enhanced and/or presynaptic autoinhibitory responses are attenuated. However, autoradiographic analyses of 8-OH-DPAT binding in the SCN and midbrain raphe have provided no evidence for upregulation or downregulation of 5-HT receptors by brief LL (11,22). Changes at the level of second messengers remain possible, but there could be a more general mechanism at work.…”

“…In this issue of the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Knoch et al (22) report their third in a recent series of studies in which they describe and pharmacologically characterize a marked potentiation of nonphotic phase shifting in Syrian hamsters by one or two nights of exposure to constant light (brief LL). The inspiration for testing this effect of light was empirically grounded, as follows.…”