Light-induced phase shift in the Syrian hamster (Mesocricetus auratus) is attenuated by the PACAP receptor antagonist PACAP6-38 or PACAP immunoneutralization

Eur J Neurosci. 2003 Nov;18(9):2552-62. doi: 10.1046/j.1460-9568.2003.03000.x.

Abstract

Circadian rhythms generated by the suprachiasmatic nucleus (SCN) are daily adjusted (entrained) by light via the retinohypothalamic tract (RHT). The RHT contains two neurotransmitters, glutamate and pituitary adenylate cyclase-activating polypeptide (PACAP), which are believed to mediate the phase-shifting effects of light on the clock. In the present study we have elucidated the role of PACAP in light-induced phase shifting at early night in hamsters and shown that (i) light-induced phase delay of running-wheel activity was significantly attenuated by a specific PAC1 receptor antagonist (PACAP6-38) or by immunoblockade with a specific anti-PACAP antibody injected intracerebroventricularly before light stimulation; (ii) PACAP administered close to the SCN was able to phase-delay the circadian rhythm of running-wheel activity in a similar way to light; (iii) PACAP was present in the hamster RHT, colocalized with melanopsin, a recently identified opsin which has been suggested to be a circadian photopigment. The findings indicate that PACAP is a neurotransmitter of the RHT mediating photic information to the clock, possibly via melanopsin located exclusively on the PACAP-expressing cells of the RHT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Behavior, Animal
  • Circadian Rhythm / drug effects*
  • Circadian Rhythm / physiology
  • Cricetinae
  • Hypothalamus / physiology*
  • Immunohistochemistry
  • Light*
  • Male
  • Mesocricetus
  • Neural Pathways / chemistry
  • Neural Pathways / physiology
  • Neurons / drug effects
  • Neuropeptides / administration & dosage
  • Neuropeptides / analysis
  • Neuropeptides / immunology
  • Neuropeptides / pharmacology*
  • Neuropeptides / physiology*
  • Neurotransmitter Agents / analysis
  • Peptide Fragments / pharmacology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Pituitary Hormone / antagonists & inhibitors
  • Retina / chemistry
  • Retina / physiology*
  • Rod Opsins / drug effects
  • Rod Opsins / physiology
  • Running
  • Suprachiasmatic Nucleus / drug effects*
  • Synaptic Transmission / drug effects

Substances

  • Antibodies
  • Neuropeptides
  • Neurotransmitter Agents
  • Peptide Fragments
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Receptors, Pituitary Hormone
  • Rod Opsins
  • melanopsin
  • pituitary adenylate-cyclase-activating-peptide (6-38)