Lesions of the suprachiasmatic nucleus eliminate the daily rhythm of hypocretin-1 release.
OBJECTIVE
Hypocretins (orexins) are involved in the sleep disorder narcolepsy. While hypocretin-1 has a daily oscillation, little is known regarding the relative contribution of circadian and homeostatic components on hypocretin release. The effect of lesions of the suprachiasmatic nucleus (SCN) on hypocretin-1 in the cerebrospinal fluid (CSF) was examined.


METHODS
SCN-ablated (SCNx) and sham-operated control rats were implanted with activity-temperature transmitters. Animals were housed individually under 1 of 3 lighting conditions: 12-hour:12-hour light:dark cycle (LD), constant light (LL), and constant darkness (DD). Lesions were verified histologically and shown not to affect hypocretin-containing cells. Hypocretin-1 concentrations in the CSF were determined every 4 hours using radioimmunoassays.


RESULTS
Control animals displayed robust circadian (LL, DD) and diurnal (LD) fluctuations in CSF hypocretin-1, locomotor activity, and temperature. Peak CSF hypocretin-1 was at the end of the active period. Activity, temperature, and CSF hypocretin-1 were arrhythmic in SCNx animals in LL and DD. In LD, a weak but significant fluctuation in activity and temperature but not CSF hypocretin-1 was observed in SCNx animals. We also explored correlations between CSF hypocretin-1, CSF corticosterone, and locomotor activity occurring prior to CSF sampling in arrhythmic SCNx rats under constant conditions. Significant correlations between hypocretin-1 and activity were observed both across and within animals, suggesting that interindividual and time-of-the-day differences in activity have significant effects on hypocretin release in arrhythmic animals. No correlation was found between CSF hypocretin-1 and corticosterone.


CONCLUSIONS
Hypocretin-1 release is under SCN control. Locomotor activity influences the activity of the hypocretin neurons.
Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Palo Alto, CA, USA.
Shengwen
S
Zhang
Jamie M
JM
Zeitzer
Yasushi
Y
Yoshida
Jonathan P
JP
Wisor
Seiji
S
Nishino
Dale M
DM
Edgar
Emmanuel
E
Mignot
D000818:Animals; D001831:Body Temperature / Q000502:physiology; D002352:Carrier Proteins / Q000134:cerebrospinal fluid / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins; D008124:Locomotion / Q000502:physiology; D009290:Narcolepsy / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000473:pathology; D009479:Neuropeptides / Q000134:cerebrospinal fluid / Q000378:metabolism*; D000068797:Orexins; D011863:Radioimmunoassay; D051381:Rats; D013493:Suprachiasmatic Nucleus / Q000473:pathology*
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins