Orexin-SAP References

Cat #IT-20


Takeuchi Y, Nagy AJ, Barcsai L, Li Q, Ohsawa M, Mizuseki K, Berényi A (2021) The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies. Front Neural Circuits 15:701080. doi: 10.3389/fncir.2021.701080

Summary: The medial septum (MS) may be a potential target for treating neurological and psychiatric disorders with abnormal oscillations (oscillopathies) to restore healthy patterns or erase undesired ones. The time-targeted strategy for the MS stimulation may provide an effective way of treating multiple disorders.
Dose: 192-IgG-SAP. The MS cholinergic neurons along with theta oscillations are known to be essential for memory because selective lesion of the cholinergic neurons resulted in spatial memory impairments (150 ng; Easton et al., 2011)  (5.04 μg icv; Jeong et al., 2014). Orexin-SAP. The enhanced gamma oscillations and altered PPI and auditory gating created by psychoactive drugs in rats were mediated by GABAergic neurons in the MS because they were abolished by ablation of these neurons by Orexin-SAP (140 ng total bilateral; Ma et al., 2012). mu p75-SAP. Anxious environment-induced type 2 theta oscillation and associated anxiety were shown to be dependent on the MS cholinergic neurons because lesion of MS cholinergic neurons reduced them (0.65 or 1.3 µg, bilateral; Nag et al., 2009).

Wang YQ, Liu WY, Li L, Qu WM, Huang ZL (2021) Neural circuitry underlying REM sleep: A review of the literature and current concepts. Prog Neurobiol 204:102106. doi: 10.1016/j.pneurobio.2021.102106

Summary: To investigate the role of the LC in sleep the authors injected 0.3 µl of 192-Saporin (Cat. IT-01) or anti-DBH-SAP (Cat. #IT-03) at 1 µg/µl. They also used 0.3 µl of orexin-SAP (Cat. #IT-20) at either 90 ng/µl or 60 ng/µl in a separate group of animals. The results indicate that orexin innervation to the pons plays a role in arousal from sleep.

See: Blanco-Centurion C et al. Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone. Eur J Neurosci 19(10):2741-2752, 2004.

Xu Q, Wang DR, Dong H, Chen L, Lu J, Lazarus M, Cherasse Y, Chen GH, Qu WM, Huang ZL (2021) Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats. Front Neurosci 15:645877.

Summary: Lesions of the LC with 192-IgG-SAP have no significant effect on wakefulness in rats (see Blanco-Centurion et al. 2007). Only the Orexin-SAP lesion involved in the MPB region resulted in the dramatic decrease of wakefulness in rats (See Fuller et al. 2011).


Cui S-Y, Huang Y-L, Cui X-Y, Zhao H-L, Hu X, Liu Y-T, Qin Y, Kurban N, Zhang Y-H (2020) A common neuronal mechanism of hypertension and sleep disturbances in spontaneously hypertensive rats: Role of orexinergic neurons. Prog Neuropsychopharmacol Biol Psychiatry 100:109902. doi: 10.1016/j.pnpbp.2020.109902

Objective: To investigate dynamic changes in sleep patterns during the development of hypertension.
Summary: Although the correlation between sleep disturbances and hypertension is very complex, common mechanisms may underlie these comorbidities.
Dose: Orexin-B-SAP (HCRT2-SAP) was administered in two injections/side (100 and 200 ng/0.5 μl/injection).


Benade V, Daripelli S, Tirumalasetty C, Subramanian R, Petlu S, Badange R, & Nirogi R. 0054 SUVN-G3031, a Histamine H3 Receptor Inverse Agonist Produces Wake Promoting Effect in Orexin-2-saporin Lesioned Rats. (2019) Sleep, 42 (Supplement_1):A22-A23. . doi: 10.1093/sleep/zsz067.053

Summary:  Rats lesioned with Orexin-SAP in lateral hypothalamus produced narcoleptic-like behavior.

Murillo-Rodríguez E, Millán-Aldaco D, Palomero-Rivero M, Morales-Lara D, Mechoulam R, Drucker-Colín R. Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data. (2019) CNS Neurol Disord Drug Targets 18(9):705-712. doi: 10.2174/1871527318666191021143300

Objective:  To determine whether the systemic injection of CBD (5 mg/kg, i.p.) would block the excessive sleepiness in a narcoleptic model.
Summary:  Preliminary findings suggest that CBD might prevent sleepiness in narcolepsy.
Dose:  Orexin-SAP (490 ng/0.5 μL, n= 10) was bilaterally injected into the LH of rats to eliminate HCRT leading to the establishment of narcoleptic-like behavior.

Nirogi R, Shinde A, Mohammed AR, Badange RK, Reballi V, Bandyala TR, Saraf SK, Bojja K, Manchineella S, Achanta PK, Kandukuri KK, Subramanian R, Benade V, Palacharla RC, Jayarajan P, Pandey S, Jasti V. Discovery and Development of N-[4-(1-Cyclobutylpiperidin-4-yloxy)phenyl]-2-(morpholin-4-yl)acetamide Dihydrochloride (SUVN-G3031): A Novel, Potent, Selective, and Orally Active Histamine H3 Receptor Inverse Agonist with Robust Wake-Promoting Activity. (2019) J Med Chem 62(3):1203-1217. doi: 10.1021/acs.jmedchem.8b01280

Objective:  To examine the effects of clinical candidate, 17v on sleep/wake activity in Orexin-SAP lesioned male Wistar rats.
Summary:  17v demonstrated high receptor occupancy and marked wake-promoting effects with decreased rapid-eye-movement sleep in Orexin-SAP lesioned rats supporting its potential therapeutic utility in treating human sleep disorders.
Dose:  Intracerebral injections of Orexin-B-SAP (100 ng/0.5 μl) in lateral hypothalamus of rats produce selective disruption of neurons containing orexin-B receptors and produces symptoms that are characteristic of narcolepsy.


Arias-Carrion O, Ortega-Robles E, de Celis-Alonso B, Palasz A, Mendez-Rojas MA, Salas-Pacheco J, & Murillo-Rodriguez E. Depletion of Hypocretin/Orexin Neurons Increases Cell Proliferation in the Adult Subventricular Zone. (2018). CNS & Neurological Disorders – Drug Targets- CNS & Neurological Disorders), 17 (2):106-112.

Objective:  To establish the relationship between the depletion of orexin neurons and the number of proliferating cells in the subventricular zone.
Summary:  The adult subventricular zone is affected by orexinergic signaling, the functional implication of which must be further elucidated.
Dose:  90 ng of Orexin-SAP or pyrogen-free saline was stereotaxically injected into the lateral hypothalamus (3.2 caudal, 1.7 lateral to bregma, 8.1 ventral to the skull surface) of male Wistar rats.

Oliveira LM, Falquetto B, Moreira TS, & Takakura AC. Orexinergic Neurons Are Involved in the Chemosensory Control of Breathing During the Dark Phase in a Parkinson’s Disease Model. (2018). Experimental Neurology, 309 107-118.

Objective:  To determine the involvement of orexin cells from the lateral hypothalamus/perifornical area (LH/PeF) on breathing.
Summary:  The degeneration of orexinergic neurons in this model of PD can be related to impaired chemoreceptor function in the dark phase.
Dose:  For lesions of LH/PeF, two injections of Orexin-B-SAP or Rabbit IgG-SAP (100 ng/μl) were made into the lateral hypothalamus / perifornical area (LH/PeF).


Mohammed M, Kulasekara K, Ootsuka Y, Blessing WW. (2016) Locus coeruleus noradrenergic innervation of the amygdala facilitates alerting-induced constriction of the rat tail artery. Am J Physiol Regul Integr Comp Physiol 310(11):R1109-19. PMID: 27101292 (Targeting Trends 16q3)

Schwartz MD, Nguyen AT, Warrier DR, Palmerston JB, Thomas AM, Morairty SR, Neylan TC, Kilduff TS. (2016) Locus Coeruleus and Tuberomammillary Nuclei Ablations Attenuate Hypocretin/Orexin Antagonist-Mediated REM Sleep. eNeuro 3(2) PMID: 27022631 (Targeting Trends 16q2)


Arias-Carrion O, Murillo-Rodriguez E. (2014) Effects of hypocretin/orexin cell transplantation on narcoleptic-like sleep behavior in rats. PLoS One 9(4):e95342. (Targeting Trends 14q3)

Vetrivelan R, Saper CB, Fuller PM. (2014) Armodafinil-induced wakefulness in animals with ventrolateral preoptic lesions. Nat Sci Sleep 6:57-63. (Targeting Trends 14q3)

Wheeler DS, Wan S, Miller A, Angeli N, Adileh B, Hu W, Holland PC. (2014) Role of lateral hypothalamus in two aspects of attention in associative learning. Eur J Neurosci 40(2):2359-2377. (Targeting Trends 14q3)

Zhang GH, Liu ZL, Zhang BJ, Geng WY, Song NN, Zhou W, Cao YX, Li SQ, Huang ZL, Shen LL. (2014) Orexin A activates hypoglossal motoneurons and enhances genioglossus muscle activity in rats. Br J Pharmacol 171(18):4233-4246. (Targeting Trends 14q3)


Kukkonen JP. (2013) Physiology of the orexinergic/hypocretinergic system: a revisit in 2012. Am J Physiol Cell Physiol 304(1):C2-32. (Targeting Trends 13q2)


Anaclet C, Lin JS, Vetrivelan R, Krenzer M, Vong L, Fuller PM, Lu J. (2012) Identification and characterization of a sleep-active cell group in the rostral medullary brainstem. J Neurosci 32(50):17970-17976. (Targeting Trends 13q1)

Brown RE, Basheer R, McKenna JT, Strecker RE, McCarley RW. (2012) Control of sleep and wakefulness. Physiol Rev 92(3):1087-1187. (Targeting Trends 12q4)

Ma J, Tai SK, Leung LS. (2012) Septohippocampal GABAergic neurons mediate the altered behaviors induced by n-methyl-D-aspartate receptor antagonists. Hippocampus 22(12):2208-2218. (Targeting Trends 12q4)

Olarte-Sanchez C, Valencia Torres L, Body S, Cassaday H, Bradshaw C, Szabadi E. (2012) Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule. J Psychopharmacol 26(6):871-886. (Targeting Trends 11q4)

Vetrivelan R, Fuller PM, Yokota S, Lu J, Saper CB. (2012) Metabolic effects of chronic sleep restriction in rats. Sleep 35(11):1511-1520. (Targeting Trends 13q1)


Di Sebastiano AR, Wilson-Perez HE, Lehman MN, Coolen LM (2011) Lesions of orexin neurons block conditioned place preference for sexual behavior in male rats. Horm Behav 59(1):1-8. (Targeting Trends 11q1)

Fuller P, Sherman D, Pedersen NP, Saper CB, Lu J (2011) Reassessment of the structural basis of the ascending arousal system. J Comp Neurol 519(5):933-956. doi: 10.1002/cne.22559

Summary: Traditional thought has been that electroencephalogram activity is mainly generated by the thalamo-cortical system. In this work the authors investigated the effects of basal forebrain lesions on various measurements of wakefulness. Rats received 4 50 ng injections of 192-IgG-SAP (Cat. #IT-01) into the basal forebrain. The effects of these lesions showed that the parabrachial nucleus/precoeruleus region projection relayed by the basal forebrain to the cerebral cortex plays a critical role in behavioral and electrocortical arousal.

I’anson H, Jethwa PH, Warner A, Ebling FJ. (2011) Histaminergic regulation of seasonal metabolic rhythms in Siberian hamsters. Physiol Behav 103(3-4):268-278. (Targeting Trends 11q2)

Lecourtier L, de Vasconcelos AP, Leroux E, Cosquer B, Geiger K, Lithfous S, Cassel JC. (2011) Septohippocampal pathways contribute to system consolidation of a spatial memory: Sequential implication of gabaergic and cholinergic neurons. Hippocampus 21(12):1277-1289. (Targeting Trends 10q4)

Luo T, Leung LS. (2011) Involvement of Tuberomamillary Histaminergic Neurons in Isoflurane Anesthesia. Anesthesiology 115(1):36-43. (Targeting Trends 11q3)

Ocampo-Garces A, Ibanez F, Perdomo G, Torrealba F (2011) Orexin-B-saporin lesions in the lateral hypothalamus enhance photic masking of rapid eye movement sleep in the albino rat. J Sleep Res20(1 Pt 1):3-11. (Targeting Trends 10q4)


Di Sebastiano AR, Yong-Yow S, Wagner L, Lehman MN, Coolen LM (2010) Orexin mediates initiation of sexual behavior in sexually naive male rats, but is not critical for sexual performance. Horm Behav 58(3):397-404. (Targeting Trends 10q3)

Luo T, Leung LS (2010) Endogenous Histamine Facilitates Long-Term Potentiation in the Hippocampus during Walking. J Neurosci 30(23):7845-7852. (Targeting Trends 10q3)


Arias-Carrion O, Murillo-Rodriguez E (2009) Cell transplantation: a future therapy for narcolepsy? CNS Neurol Disord Drug Targets 8:309-314. (Targeting Trends 10q1)

Kaur S, Thankachan S, Begum S, Liu M, Blanco-Centurion C, Shiromani PJ (2009) Hypocretin-2 saporin lesions of the ventrolateral periaquaductal gray (vlPAG) increase REM sleep in hypocretin knockout mice. PLoS One 4:e6346. (Targeting Trends 09q4)

Vetrivelan R, Fuller PM, Tong Q, Lu J (2009) Medullary circuitry regulating rapid eye movement sleep and motor atonia. J Neurosci 29:9361-9369. (Targeting Trends 09q4)

See also: Society for Neuroscience 2009 Abstracts


Murillo-Rodriguez E, Liu M, Blanco-Centurion C, Shiromani PJ (2008) Effects of hypocretin (orexin) neuronal loss on sleep and extracellular adenosine levels in the rat basal forebrain. Eur J Neurosci 28(6):1191-1198. (Targeting Trends 08q4)

See also: Society for Neuroscience 2008 Abstracts


Blanco-Centurion C, Gerashchenko D, Shiromani PJ (2007) Effects of saporin-induced lesions of three arousal populations on daily levels of sleep and wake. J Neurosci 27:14041-14048. (Targeting Trends 08q1)

Frederick-Duus D, Guyton MF, Fadel J (2007) Food-elicited increases in cortical acetylcholine release require orexin transmission. Neuroscience 149:499-507. (Targeting Trends 08q1)

Furlong T, Carrive P (2007) Neurotoxic lesions centered on the perifornical hypothalamus abolish the cardiovascular and behavioral responses of conditioned fear to context but not of restraint. Brain Res 1128(1):107-119. (Targeting Trends 07q1)

See also: Society for Neuroscience 2007 Abstracts


Easton A, Dwyer E, Pfaff DW (2006) Estradiol and orexin-2 saporin actions on multiple forms of behavioral arousal in female mice. Behav Neurosci 120(1):1-9. (Targeting Trends 06q2)

Gerashchenko D, Blanco-Centurion CA, Miller JD, Shiromani PJ (2006) Insomnia following hypocretin2-saporin lesions of the substantia nigra. Neuroscience 137(1):29-36. (Targeting Trends 06q1)

Lu J, Sherman D, Devor M, Saper CB (2006) A putative flip-flop switch for control of REM sleep. Nature 441(1):589-594. (Targeting Trends 07q1)

See also: Society for Neuroscience 2006 Abstracts


Lappi DA (2005) Targeted Toxins from Here to There. Targeting Trends 6(3):1, 6.

Pang K, Smith H. (2005) Effects of Intraseptal Orexin-Saporin on Spatial Memory. Targeting Trends 6(4).

Smith HR, Pang KC (2005) Orexin-saporin lesions of the medial septum impair spatial memory. Neuroscience 132(2):261-271. (Targeting Trends 05q3)

See also: Society for Neuroscience 2005 Abstracts


Blanco-Centurion C, Gerashchenko D, Salin-Pascual RJ, Shiromani PJ (2004) Effects of hypocretin2-saporin and antidopamine-beta-hydroxylase-saporin neurotoxic lesions of the dorsolateral pons on sleep and muscle tone. Eur J Neurosci 19(10):2741-2752. (Targeting Trends 04q3)

Gerashchenko D, Chou TC, Blanco-Centurion CA, Saper CB, Shiromani PJ (2004) Effects of lesions of the histaminergic tuberomammillary nucleus on spontaneous sleep in rats. Sleep 27(7):1275-1281. (Targeting Trends 05q2)


Gerashchenko K, Blanco-Centurion C, Greco MA, Shiromani PJ (2003) Effects of lateral hypothalamic lesion with the neurotoxin hypocretin-2-saporin on sleep in Long-Evans rats. Neuroscience 116:223-235. (Targeting Trends 03q2)

Gerashchenko D, Murillo-Rodriguez E, Lin L, Xu M, Hallett L, Nishino S, Mignot E, Shiromani PJ (2003) Relationship between CSF hypocretin levels and hypocretin neuronal loss. Exp Neurol 184(2):1010-1016. (Targeting Trends 04q2)

Mistlberger RE, Antle MC, Kilduff TS, Jones M (2003) Food- and light-entrained circadian rhythms in rats with hypocretin-2-saporin ablations of the lateral hypothalamus. Brain Res 980(2):161-168. (Targeting Trends 03q3)

See also: Society for Neuroscience 2003 Abstracts


Blanco-Centurion C. (2002) HCRT-SAP Lesion Produces Sleepiness While anti-DBH-SAP Lesion Does Not. Targeting Trends 3(2).

See: Society for Neuroscience 2002 Abstracts


Gerashchenko D, Kohls MD, Greco M, Waleh NS, Salin-Pascual R, Kilduff TS, Lappi DA, Shiromani PJ (2001) Hypocretin-2-Saporin Lesions of the Lateral Hypothalamus Produce Narcoleptic-Like Sleep Behavior in the Rat. J Neurosci 21(18):7273-7283. (Targeting Trends 01q4)

Gerashchenko D, Salin-Pascual R, Shiromani PJ (2001) Effects of Hypocretin-Saporin Injections into the Medial Septum on Sleep and Hippocampal Theta. Brain Res 913:106-115. (Targeting Trends 01q4)

See also: Society for Neuroscience 2001 Abstracts

See also: Society for Neuroscience 2000 Abstracts


Sakurai T, Amemiya A, Ishii M, Matsuzaki I, Chemelli RM, Tanaka H, Williams SC, Richardson JA, Kozlowski GP, Wilson s, Arch JR, Buckingham RE, Haynes AC, Carr SA, Annan RS, McNulty DE, Liu WS, Terrett JA, Elshourbagy NA, Bergsma DJ, Yanagisawa M (1998) Orexins and orexin receptors: a family of hypothalamic neuropeptides and G protein-coupled receptors that regulate feeding behavior. Cell 92:573-585.