Blanco-Centurion CA, Salin-Pascual RJ, Gerashchenko D, Greco MA, Shiromani PJ (2001) Hypocretin B-saporin lesions of the brainstem increase rem sleep at night. Neuroscience 2001 Abstracts 410.9. Society for Neuroscience, San Diego, CA.
Summary: Loss of hypocretin (Hcrt) neurons has been linked to narcolepsy. These neurons project widely throughout brain, but it is not known which projection to which target site produces what symptom of narcolepsy. We (Molec Brain Res, 88:176-182,2001) showed that Hcrt receptors are present in brainstem areas implicated in REM sleep. Since abnormal REM sleep triggering characterizes narcolepsy, we have used Hcrt-saporin, a toxin that selectively lesions Hcrt receptor bearing cells, to assess the effects of such lesions on sleep. In the present study, Sprague Dawley rats (n=21) were administered (under anesthesia) Hcrt-sap (100ng/1ul, vol=0.5 ul bilaterally) or saline to the locus subcoeruleus (LSC) or the medullary inhibitory area of Magoun and Rhines. Subsequently, continuous sleep recordings were made for 21 days. Sleep records were scored blind. In the medulla, Hcrt-sap (n=5) increased the length of REM sleep bouts (p<0.039), which produced a trend towards an increase in REM sleep at night. There were no significant changes in SWS or W. Lesions of the LSC (n=5) increased total sleep time at night (p<0.03) and produced a trend towards a REM sleep increase. Data from both target sites were combined and the Hcrt-sap lesioned rats (n=10 versus saline=11) had a significant increase in REM sleep (30%; p<0.015). At neither site, cataplectic attacks were evident. Our studies with Hcrt-sap indicate site-specific effects on sleep and EEG depending on which Hcrt-receptor bearing neurons are lesioned. All of the symptoms of narcolepsy are evident when the Hcrt-containing neurons are lost. Supported by: NS30140, AG09975, AG15853, MH55772, DVA Med Research.
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