Prolactin-releasing peptide (PrRP) promotes awakening and suppresses absence seizures.
Prolactin releasing peptide (PrRP) is a recently identified neuropeptide that stimulates prolactin release from pituitary cells. The presence of its receptor outside the hypothalamic-pituitary axis suggests that it may have other functions. We present here evidence that PrRP can modulate the activity of the reticular thalamic nucleus, a brain region with prominent PrRP receptor expression that is critical for sleep regulation and the formation of non-convulsive absence seizures. Intracerebroventricular injection of PrRP (1-10 nmol) into sleeping animals significantly suppresses sleep oscillations and promotes rapid and prolonged awakening. Higher concentrations of PrRP (10-100 nmol) similarly suppress spike wave discharges seen during absence seizures in genetic absence epilepsy rats from Strasbourg, an animal model for this disorder. In concordance with these findings, PrRP suppressed evoked oscillatory burst activity in reticular thalamic slices in vitro. These results indicate that PrRP modulates reticular thalamic function and that activation of its receptor provides a new target for therapies directed at sleep disorders and absence seizures.
Department of Pharmacology, University of California, Irvine, Med Surge II, Room 369, Irvine, CA 92697-4855, USA.
S H S
SH
Lin
A C
AC
Arai
R A
RA
España
C W
CW
Berridge
F M
FM
Leslie
J R
JR
Huguenard
M
M
Vergnes
O
O
Civelli
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D004569:Electroencephalography / Q000187:drug effects; D004832:Epilepsy, Absence / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D007028:Hypothalamic Hormones / Q000378:metabolism* / Q000494:pharmacology; D020646:Intralaminar Thalamic Nuclei / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D009924:Organ Culture Techniques; D056690:Prolactin-Releasing Hormone; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011922:Rats, Mutant Strains; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D012890:Sleep / Q000187:drug effects / Q000502:physiology; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D014851:Wakefulness / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis
D007028:Hypothalamic Hormones; D007527:Isoenzymes; D009479:Neuropeptides; C534379:Prlh protein, rat; D056690:Prolactin-Releasing Hormone; D012333:RNA, Messenger; D018013:Receptors, Neuropeptide; C400801:receptor, prolactin-releasing peptide; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1