title: Substance P receptor antagonist in lateral habenula improves rat depression-like behavior.
abstract: Substance P (SP) levels are closely related with the pathogenesis of depression. Recent work has focused on antidepressive effect of substance P receptor antagonist (SPA), however, its action site and mechanism remain largely unresolved. Our previous results showed that the lateral habenula (LHb) plays a key role in the pathogenesis of depression. The current study investigated the effects of SPA microinjected into LHb on the behavioral responses of two rat models that exhibit depression-like behavior. To produce adult rats that exhibit depression-like behavior, rats were either exposed to chronic mild stress (CMS), or chronically administered clomipramine (CLI), a tricyclic antidepressant, during the neonatal state of life. The forced-swimming test (FST) was used to evaluate behavioral responses. Furthermore, we measured serotonin (5-HT) levels in dorsal raphe nucleus (DRN) using microdialysis. The FST showed a decreased immobility time and an increased climbing time after SPA injection into the LHb of depression-like behavior rats. In addition, 5-HT levels in DRN increased after SPA was microinjected into LHb of the rats that exhibited depression-like behavior. This study demonstrates that LHb mediates antidepressive effect of SPA by increasing 5-HT levels in the DRN, suggesting that the LHb may be a potential target of antidepressant.
authors.affiliation: Department of Physiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Yang
authors.affiliation: Department of Physiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Physiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Department of Physiology, Norman Bethune College of Medicine, Jilin University, Changchun 130021, PR China; Neuroscience Research Center, First Hospital of Jilin University, Changchun 130021, PR China. Electronic address: zhua@jlu.edu.cn.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003863:Depression / Q000378:metabolism*; D004195:Disease Models, Animal; D019262:Habenula / Q000187:drug effects* / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D017551:Microdialysis; D008845:Microinjections; D064729:Neurokinin-1 Receptor Antagonists / Q000008:administration & dosage*; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000032:analysis / Q000378:metabolism; D013373:Substance P / Q000378:metabolism
chemical_list: D064729:Neurokinin-1 Receptor Antagonists; D012701:Serotonin; D013373:Substance P
keywords: Depression-like behavior; Dorsal raphe nucleus; Lateral habenula; Serotonin; Substance P; Substance P receptor antagonist