The European journal of neuroscienceFeb 24, 2001

Vasoactive intestinal polypeptide shifts the timing of the rat's brain internal clock in a lab setting

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 25, 2026

Abstract

Application of vasoactive intestinal polypeptide (VIP) during the early or late subjective night resulted in a small phase delay or a large phase advance, respectively, in rat SCN neuron firing rates.

VIP does not shift the peak firing rate rhythm when applied during the subjective day.
The phase-advancing effect of VIP is attributed to the VPAC(2) receptor, as shown with the selective agonist RO 25-1553.
Neither the PAC(1) receptor agonist nor the VPAC(1) receptor agonist produced a similar phase-resetting effect.
VIP phase-dependently resets the electrical activity rhythm of SCN neurons in vitro.
The findings suggest a potential role for VIP and the VPAC(2) receptor in synchronizing the rodent circadian clock with light.

Simplified

In mammals, the principal circadian pacemaker is housed in the hypothalamic suprachiasmatic nuclei (SCN). The SCN exhibit high levels of vasoactive intestinal polypeptide (VIP) immunoreactivity and two of the three VIP receptors, VPAC(2) and PAC(1), are found in the rat SCN. However, the role of VIP in the SCN remains unclear. In this study, we examined the phase-resetting actions of VIP and selective VIP receptor agonists on the electrical activity rhythm of rat SCN neurons in vitro. Application of VIP during the subjective day did not shift the peak in the firing rate rhythm. However, VIP treatment during the early or late subjective night evoked a small phase delay or a large phase advance, respectively. The phase-advancing effect of VIP was reproduced by the novel VPAC(2) receptor agonist RO 25-1553, but not by pituitary adenylate cyclase-activating peptide (a potent PAC(1) receptor agonist), or by [K15,R16,L27]VIP(1-7)/GRF(8-27), a novel, selective VPAC(1) receptor agonist. These data show that VIP phase-dependently phase-resets the rodent SCN pacemaker in vitro, presumably via the VPAC(2) receptor. As the pattern of phase-shifting evoked by VIP and RO 25-1553 resembles the phase-resetting actions of light on rodent behavioural rhythms, these data support a role for VIP and the VPAC(2) receptor in photic entrainment of the rodent circadian pacemaker.

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Vasoactive intestinal polypeptide shifts the timing of the rat's brain internal clock in a lab setting

Abstract

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