Short‐term constant light potentiation of large‐magnitude circadian phase shifts induced by 8‐OH‐DPAT: effects on serotonin receptors and gene expression in the hamster suprachiasmatic nucleus

Nov 3, 2005The European journal of neuroscience

Short-term constant light increases large daily rhythm shifts caused by 8-OH-DPAT, affecting serotonin receptors and gene activity in the hamster’s internal clock

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Abstract

Approximately 2 days of constant light exposure significantly influenced the expression of key circadian genes in the suprachiasmatic nucleus.

Constant light exposure did not affect 5-HT7 receptor binding in the suprachiasmatic nucleus or dorsal raphe.
No changes were observed in 5-HT1A autoreceptors in the median raphe or 5-HT1B receptors in the suprachiasmatic nucleus due to constant light.
The serotonin agonist 8-OH-DPAT suppressed the expression of Per1 and Per2 mRNAs in the suprachiasmatic nucleus.
Constant light alone also suppressed Per1 mRNA levels.
Constant light exposure significantly reduced arginine vasopressin mRNA but did not affect vasoactive intestinal polypeptide mRNA.
The suppression of SCN Per1 mRNA and arginine vasopressin mRNA may enhance the effectiveness of phase-shifting stimuli.

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Nonphotic phase-shifting of mammalian circadian rhythms is thought to be mediated in part by serotonin (5-HT) acting in the suprachiasmatic nucleus (SCN) circadian clock. Previously we showed that brief (1-3 days) exposure to constant light (LL) greatly potentiates nonphotic phase-shifting induced by the 5-HT agonist, (+/-)2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT). Here we investigated potential mechanisms for this action of LL, including 5-HT receptor upregulation and SCN clock gene and neuropeptide gene expression. Autoradiographic analysis of ritanserin inhibition of [3H]8-OH-DPAT binding indicated that LL (approximately 2 days) did not affect 5-HT7 receptor binding in the SCN or dorsal raphe. Measurement of 5-HT1A autoreceptors in the median raphe and 5-HT1B receptors in the SCN also showed no effect of LL. In experiment 2, hamsters held under a 14-h light : 10-h dark photocycle (LD) or exposed to LL for approximately 2 days received an intraperitoneal injection of 8-OH-DPAT or vehicle at zeitgeber time (ZT) 6 or 0 and were killed after 2 h of dark exposure. 8-OH-DPAT suppressed SCN Per1 and Per2 mRNAs at both ZTs, as assessed by in situ hybridization. Per1 mRNA was also suppressed by LL alone. In addition, in situ hybridization of arginine vasopressin (AVP) mRNA and vasoactive intestinal polypeptide mRNA showed that LL significantly suppressed the former but not the latter. The LL-induced suppression of SCN Per1 mRNA and AVP mRNA may be involved in LL-induced potentiation of pacemaker resetting, especially as these data provide additional evidence that LL suppresses circadian pacemaker amplitude, thus rendering the clock more susceptible to phase-shifting stimuli.

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Short‐term constant light potentiation of large‐magnitude circadian phase shifts induced by 8‐OH‐DPAT: effects on serotonin receptors and gene expression in the hamster suprachiasmatic nucleus

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