Light-induced phase shift in the Syrian hamster (Mesocricetus auratus) is attenuated by the PACAP receptor antagonist PACAP6-38 or PACAP immunoneutralization.
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.
Bergström
A L
AL
Department of Clinical Biochemistry, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark.
Hannibal
J
J
Hindersson
P
P
Fahrenkrug
J
J
D000818:Animals; D000906:Antibodies; D001522:Behavior, Animal; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae; D007031:Hypothalamus / Q000502:physiology*; D007150:Immunohistochemistry; D008027:Light; D008297:Male; D008647:Mesocricetus; D009434:Neural Pathways / Q000737:chemistry / Q000502:physiology; D009474:Neurons / Q000187:drug effects; D009479:Neuropeptides / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology / Q000494:pharmacology* / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000032:analysis; D010446:Peptide Fragments / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone / Q000037:antagonists & inhibitors; D012160:Retina / Q000737:chemistry / Q000502:physiology*; D017299:Rod Opsins / Q000187:drug effects / Q000502:physiology; D012420:Running; D013493:Suprachiasmatic Nucleus / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects; D000099210:Melanopsin
D000906:Antibodies; D009479:Neuropeptides; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D051237:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I; D011979:Receptors, Pituitary Hormone; D017299:Rod Opsins; D000099210:Melanopsin; C075647:pituitary adenylate-cyclase-activating-peptide (6-38)