title: Orexin-A increases the activity of globus pallidus neurons in both normal and parkinsonian rats.
abstract: Orexin is a member of neuropeptides which was first identified in the hypothalamus. The globus pallidus is a key structure in the basal ganglia, which is involved in both normal motor function and movement disorders. Morphological studies have shown the expression of both OX1 and OX2 receptors in the globus pallidus. Employing single unit extracellular recordings and behavioural tests, the direct in vivo electrophysiological and behavioural effects of orexin-A in the globus pallidus were studied. Micro-pressure administration of orexin-A significantly increased the spontaneous firing rate of pallidal neurons. Correlation analysis revealed a negative correlation between orexin-A induced excitation and the basal firing rate. Furthermore, application of the specific OX1 receptor antagonist, SB-334867, decreased the firing rate of pallidal neurons, suggesting that endogenous orexinergic systems modulate the firing activity of pallidal neurons. Orexin-A increased the excitability of pallidal neurons through both OX1 and OX2 receptors. In 6-hydroxydopamine parkinsonian rats, orexin-A-induced increase in firing rate of pallidal neurons was stronger than that in normal rats. Immunostaining revealed positive OX1 receptor expression in the globus pallidus of both normal and parkinsonian rats. Finally, postural test showed that unilateral microinjection of orexin-A led to contralateral deflection in the presence of systemic haloperidol administration. Further elevated body swing test revealed that pallidal orexin-A and SB-334867 induced contralateral-biased swing and ipsilateral-biased swing respectively. Based on the electrophysiological and behavioural findings of orexin-A in the globus pallidus, the present findings may provide a rationale for the pathogenesis and treatment of Parkinson's disease.
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Yang
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.|Department of Pathology, Qingdao Municipal Hospital, Qingdao, China.
authors.forename: Hong-Yun
authors.initials: HY
authors.lastname: Liu
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: An-Qi
authors.initials: AQ
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Qing
authors.identifier: 0000-0003-1558-8938
authors.initials: Q
authors.lastname: Sheng
authors.affiliation: Department of Neurology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China.
authors.forename: Xin-Yi
authors.initials: XY
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, Qingdao Municipal Hospital, Qingdao, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Liu
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Ya-Yan
authors.initials: YY
authors.lastname: Pang
authors.affiliation: Department of Physiology, Faculty of Medicine, Qingdao University, Qingdao 266071, Shandong, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
mesh_terms: D000200:Action Potentials; D000818:Animals; D001583:Benzoxazoles / Q000494:pharmacology; D005917:Globus Pallidus / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D000068796:Orexin Receptor Antagonists / Q000494:pharmacology; D064446:Orexin Receptors / Q000378:metabolism; D000068797:Orexins / Q000378:metabolism* / Q000494:pharmacology; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004856:Postural Balance; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C420062:1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea; D001583:Benzoxazoles; D009287:Naphthyridines; D000068796:Orexin Receptor Antagonists; D064446:Orexin Receptors; D000068797:Orexins; D016627:Oxidopamine; D014508:Urea; D006220:Haloperidol
keywords: OX receptor; globus pallidus; orexin-A; single unit recording