title: Panax quinquefolium involves nitric oxide pathway in olfactory bulbectomy rat model.
abstract: Olfactory bulbectomy (OBX) is a well known screening model for depression. Panax quinquefolium (PQ) is known for its therapeutic potential against several psychiatric disorders. Nitric oxide (NO), an intercellular messenger has been suggested to play a crucial role in the pathogenesis of depression. The present study was designed to explore the possible involvement of NO mechanism in the protective effect of PQ against olfactory bulbectomy induced depression. Wistar rats were bulbectomized surgically and kept for a rehabilitation period of two weeks. PQ (50, 100 and 200mg/kg; p.o.) alone and in combination with NO modulators like l-NAME (10mg/kg, i.p.) and l-arginine (100mg/kg; i.p.) were then administered daily for another two weeks. Ablation of olfactory bulbs caused depression-like symptoms as evidenced by increased immobility time in forced swim test, hyperactivity in open field arena, and anhedonic like response in sucrose preference test. Further, OBX caused elevation in serum corticosterone levels and increased oxidative-nitrosative damage. These deficits were integrated with increased levels of neuroinflammatory cytokines (TNF-α), apoptotic factor (caspase-3) and a marked reduction in neurogenesis factor (BDNF) in both cerebral cortex and hippocampal regions of bulbectomized rats. Treatment with PQ significantly and dose-dependently restored these behavioral, biochemical and molecular alterations associated with OBX. Further, pretreatment of l-NAME with subeffective dose of PQ (100mg/kg) significantly potentiated its protective effects; however l-arginine pretreatment reversed the beneficial effects. The present study suggests that protective effect of P. quinquefolium might involve nitric oxide modulatory pathway against olfactory bulbectomy-induced depression in rats.
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India.
authors.forename: Puneet
authors.initials: P
authors.lastname: Rinwa
authors.affiliation: Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India. Electronic address: kumaruips@yahoo.com.
authors.forename: Anil
authors.initials: A
authors.lastname: Kumar
mesh_terms: D059445:Anhedonia / Q000187:drug effects; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009830:Olfactory Bulb / Q000503:physiopathology / Q000601:surgery; D005894:Panax; D008517:Phytotherapy; D028321:Plant Preparations / Q000494:pharmacology*; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D028321:Plant Preparations; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone
keywords: Immobility time; Neuroinflammatory cytokines; Nitric oxide; Olfactory bulbectomy; Oxidative damage