Blanco-Centurion CA, Salin-Pascual R, Gerashchenko D, Greco MA, Lappi DA, Kilduff TS, Shiromani PJ (2000) DBH-saporin lesions the locus coeruleus, but does not produce cataplexy or abnormal REM sleep triggering. Neuroscience 2000 Abstracts 566.17. Society for Neuroscience, New Orleans, LA.
Summary: Recently, canine narcolepsy was associated with a mutation in the hypocretin-2 receptor (Lin et al., 1999), which binds the neuropeptide hypocretin, also known as orexin. The locus coeruleus receives a very heavy projection of HCRT/OX fibers, and the LC also contains HCRT/OX receptor mRNA. Silence of LC neurons is hypothesized to be key in triggering cataplexy and REM sleep. To test this hypothesis, DBH-saporin was used to selectively lesion the LC. Male Sprague-Dawley rats (400-450 g) instrumented for recording sleep were given DBH-saporin (n=4) (500ng/0.5ul) via a micropipette to the LC. Control rats were administered 192-saporin (n=3), or saline (n=4). Two days later, sleep recordings were obtained for 7 consecutive days. The rat’s behavior was videotaped at night. To identify whether cataplexy was induced, the alpha antagonist, Prazosin was administered (1500h, 500mg/kg, IP) and then sleep and video recordings were made for three hours. Brains were removed for histology. DBH-saporin completely lesioned the LC neurons. However, there were no changes in wakefulness, nonREM or REM sleep. Video recordings also did not reveal any cataplexy episodes. The application of Prazosin did not induce cataplexy or diminish muscle tone in DBH-saporin LC treated rats. Historically, LC lesions have never been found to induce cataplexy. Use of DBH-saporin provides a more specific lesion restricted to the LC neurons where the HCRT/OX receptor mRNA is localized. Our findings indicate that LC neurons are not essential for maintaining muscle tone or wakefulness.
Related Products: Anti-DBH-SAP (Cat. #IT-03)