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B inhibitor peptide
inhibits spontaneous and interleukin-1
-induced sleep
Department of Veterinary and Comparative Anatomy, Pharmacology, and Physiology, Washington State University College of Veterinary Medicine, Pullman, Washington 99164-6520
Nuclear factor-
B (NF-B)
is a transcription factor that when activated promotes production of
several sleep-promoting substances such as interleukin-1
(IL-1),
tumor necrosis factor-
, and nerve growth factor. Therefore, we
hypothesized that inhibition of NF-B activation would attenuate
sleep. A NF-B cell-permeable inhibitor peptide (IP) was injected
intracerebroventricularly (5 and 50 µg for rats, 100 µg for
rabbits). On a separate day, time-matched control injections of a
cell-permeable inactive control peptide were done in the same animals.
The 50-µg dose of IP in rats and the 100-µg dose in rabbits
significantly inhibited non-rapid eye movement sleep and rapid eye
movement sleep if administered during the light period. Moreover,
pretreatment of rabbits with 100 µg of the IP 12 h before
intracerebroventricular injection of IL-1 (10 ng) significantly
attenuated IL-1-induced sleep and febrile responses. The current
data support the hypothesis that a brain cytokine network is involved
in sleep regulation and that NF-B is a crucial factor in
physiological sleep regulation.
electroencephalogram; power density; rapid eye movement sleep; rabbits; rats
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