Gerashchenko D, Greco MA, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ (2000) Orexin-B conjugated to saporin lesions LH and TMN neurons and produces narcoleptic-like sleep in rats. Neuroscience 2000 Abstracts 566.27. Society for Neuroscience, New Orleans, LA.
Summary: A dysfunction of the hypocretin/orexin (Hcrt/Ox) system was recently linked with the sleep disorder, narcolepsy. To provide an experimental method that could be used to inactivate Hcrt/Ox receptor bearing neurons, we linked the toxin, saporin, to the orexin receptor binding ligand, orexin-B. Eighteen male Sprague-Dawley rats (400-450 g) were administered orexin-saporin (0.5 ul; 490 ng) to the lateral hypothalamus (LH) (where Hcrt/Ox containing neurons are located) or tuberomammillary nucleus (TMN) (where Hcrt/Ox receptor containing neurons are present) and sleep was recorded for 3 weeks. A significant reduction in the numbers of TMN and Hcrt/Ox neurons in the LH was detected 3 to 5 days after toxin administration and complete loss occurred by 2 weeks. Rats with extensive cell loss exhibited more REM sleep, nonREM sleep, and multiple sleep onset REM periods during the night. In the only two available animal models of human narcolepsy, the dysfunction in the orexin system is inherited and in the entire animal which makes it difficult to localize specific brain regions or circuits underlying narcolepsy. Orexin-saporin provides a method of determining the contribution of a specific Hcrt/Ox innervation in the regulation of behavior.
Related Products: Orexin-B-SAP (Cat. #IT-20)