Neonatal REM sleep is regulated by corticotropin releasing factor.

Sleep/wake regulation is quite different during the neonatal and adult periods. Although cholinergic neurons have been recognized to be the major source of rapid eye movement (REM) sleep regulation in adulthood, their effect on neonatal REM sleep remains to be discovered. Current evidence suggests that corticotropin-releasing factor (CRF) may play a role in REM promotion during the neonatal period. We conducted the following study to test our hypothesis that blocking CRF R1 receptor would reduce REM sleep in developing rat pups. First, rat pups were surgically implanted with electrodes on postnatal day (PN) 13. On PN 14, six hours of polysomnographic (PSG) data were collected before and after administration of three different doses of NBI 27914 (NBI), a CRF R1 receptor antagonist. Compared with baseline, REM sleep was significantly reduced in all groups treated with NBI but not with dimethyl sulfoxide/saline. The reduction of REM sleep was dose-related and was replaced primarily by non-REM (NREM) sleep. Second, two groups of rat pups were given a single dose of either NBI or vehicle on PN 14 for quantification of ACTH and acetylcholine without PSG recording. NBI induced no change of either ACTH or acetylcholine. Third, the effect of administering atropine (6 mg/kg) on sleep/wake in two-week-old rats was investigated. Atropine suppressed REM sleep significantly and increased wakefulness simultaneously. Our data revealed that blockage of CRF R1 receptors deprives neonatal REM sleep. The mechanism for CRF in enhancing REM sleep may be associated with but not be similar to the cholinergic mechanism.