5HT(1B) receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c- fos in the suprachiasmatic nucleus

Gary E. Pickard, E. Todd Weber, Paul A. Scott, Anne F. Riberdy, Michael A. Rea

Research output: Contribution to journalArticle

123 Citations (Scopus)

Abstract

The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical component of the mammalian circadian system. It receives afferents from the retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment of the SCN, whereas the serotonergic afferents originating from the midbrain modulate photic responses in the SCN; however, the serotonin (5HT) receptor subtypes in the SCN responsible for these modulatory effects are not well characterized. In this study, we tested the hypothesis that 5HT(1B) receptors are located presynaptically on retinal axon terminals in the SCN and that activation of these receptors inhibits retinal input. The 5HT(1B) receptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points. This inhibition was not affected by previous systemic application of either the selective 5HT(1A) receptor antagonist (P)WAY 100135 or by the 5HT2 receptor antagonist mesulergine, whereas pretreatment with the nonselective 5HT1 antagonist methiothepin significantly attenuated the effect of TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos expression in the SCN, although a small subset of cells in the dorsolateral aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mM) infused into the SCN produced complete inhibition of light-induced phase advances. Finally, bilateral orbital enucleation reduced the density of SCN 5HT(1B) receptors as determined using [125I]-iodocyanopindolol to define 5HT(1B) binding sites. These results are consistent with the interpretation that 5HT(1B) receptors are localized presynaptically on retinal terminals in the SCN and that activation of these receptors by 5HT(1B) agonists inhibits retinohypothalamic input.

Original languageEnglish (US)
Pages (from-to)8208-8220
Number of pages13
JournalJournal of Neuroscience
Volume16
Issue number24
StatePublished - Dec 15 1996

Fingerprint

Suprachiasmatic Nucleus
Immediate-Early Genes
Circadian Rhythm
Light
Iodocyanopindolol
Methiothepin
Serotonin Receptors
Presynaptic Terminals
Mesencephalon
Retina
Binding Sites

Keywords

  • 5HT(1B)
  • CGS 12066A
  • TFMPP
  • [I]-iodocyanopindolol
  • c-fos
  • circadian rhythm
  • photic entrainment
  • presynaptic
  • retinal afferents
  • suprachiasmatic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

5HT(1B) receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c- fos in the suprachiasmatic nucleus. / Pickard, Gary E.; Weber, E. Todd; Scott, Paul A.; Riberdy, Anne F.; Rea, Michael A.

In: Journal of Neuroscience, Vol. 16, No. 24, 15.12.1996, p. 8208-8220.

Research output: Contribution to journalArticle

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abstract = "The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical component of the mammalian circadian system. It receives afferents from the retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment of the SCN, whereas the serotonergic afferents originating from the midbrain modulate photic responses in the SCN; however, the serotonin (5HT) receptor subtypes in the SCN responsible for these modulatory effects are not well characterized. In this study, we tested the hypothesis that 5HT(1B) receptors are located presynaptically on retinal axon terminals in the SCN and that activation of these receptors inhibits retinal input. The 5HT(1B) receptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points. This inhibition was not affected by previous systemic application of either the selective 5HT(1A) receptor antagonist (P)WAY 100135 or by the 5HT2 receptor antagonist mesulergine, whereas pretreatment with the nonselective 5HT1 antagonist methiothepin significantly attenuated the effect of TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos expression in the SCN, although a small subset of cells in the dorsolateral aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mM) infused into the SCN produced complete inhibition of light-induced phase advances. Finally, bilateral orbital enucleation reduced the density of SCN 5HT(1B) receptors as determined using [125I]-iodocyanopindolol to define 5HT(1B) binding sites. These results are consistent with the interpretation that 5HT(1B) receptors are localized presynaptically on retinal terminals in the SCN and that activation of these receptors by 5HT(1B) agonists inhibits retinohypothalamic input.",
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T1 - 5HT(1B) receptor agonists inhibit light-induced phase shifts of behavioral circadian rhythms and expression of the immediate-early gene c- fos in the suprachiasmatic nucleus

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AU - Weber, E. Todd

AU - Scott, Paul A.

AU - Riberdy, Anne F.

AU - Rea, Michael A.

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AB - The suprachiasmatic nucleus (SCN) is a circadian oscillator and a critical component of the mammalian circadian system. It receives afferents from the retina and the mesencephalic raphe. Retinal afferents mediate photic entrainment of the SCN, whereas the serotonergic afferents originating from the midbrain modulate photic responses in the SCN; however, the serotonin (5HT) receptor subtypes in the SCN responsible for these modulatory effects are not well characterized. In this study, we tested the hypothesis that 5HT(1B) receptors are located presynaptically on retinal axon terminals in the SCN and that activation of these receptors inhibits retinal input. The 5HT(1B) receptor agonists TFMPP and CGS 12066A, administered systemically, inhibited light-induced phase shifts of the circadian activity rhythm in a dose-dependent manner at phase delay and phase advance time points. This inhibition was not affected by previous systemic application of either the selective 5HT(1A) receptor antagonist (P)WAY 100135 or by the 5HT2 receptor antagonist mesulergine, whereas pretreatment with the nonselective 5HT1 antagonist methiothepin significantly attenuated the effect of TFMPP. TFMPP also produced a dose-dependent reduction in light-stimulated Fos expression in the SCN, although a small subset of cells in the dorsolateral aspect of the caudal SCN were TFMPP-insensitive. TFMPP (1 mM) infused into the SCN produced complete inhibition of light-induced phase advances. Finally, bilateral orbital enucleation reduced the density of SCN 5HT(1B) receptors as determined using [125I]-iodocyanopindolol to define 5HT(1B) binding sites. These results are consistent with the interpretation that 5HT(1B) receptors are localized presynaptically on retinal terminals in the SCN and that activation of these receptors by 5HT(1B) agonists inhibits retinohypothalamic input.

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