title: The differential role of NOS inhibitors on stress-induced anxiety and neuroendocrine alterations in the rat.
abstract: The inhibitors of nitric oxide synthase (NOS) have been shown to possess antidepressant- and anxiolytic-properties in animal model. In order to examine the involvement of nitric oxide (NO) on stress-induced neurobehavioral changes and the concomitant alterations of neuroendocrinological factors, we studied the effects of the nonselective NOS inhibitor, N(ω)-Nitro L-arginine methyl ester hydrochloride (L-NAME) and the specific neuronal NOS inhibitor, 7-nitroindazole (7-NI) on restraint stress-induced anxiety in the elevated plus maze (EPM) test and biochemical analysis. Restraint stress significantly reduced the latency time in open arm and the percentage of open arm entries of the plus maze. Pretreatment with L-NAME (10 mg/kg) or 7-NI (10 mg/kg) significantly attenuated stress-induced anxiety response. In addition, administration of L-NAME (10 mg/kg) reversed stress-induced increase in corticosterone and NO metabolites (NO(x)) in plasma. The administration of 7-NI, but not L-NAME, reversed stress-induced NO(x) in paraventricular nucleus of the hypothalamus (PVN) and locus coeruleus (LC), accompanying with decrease of NADPH-d reactivity in the PVN and lateral dorsal tegmental nucleus (LTDg). These results showed that L-NAME influences HPA axis activity such as corticosterone levels and NO(x) in plasma, whereas 7-NI produced anxiolytic-like effects through the direct reduction in NO(x) in the brain. The results of this study demonstrated that NOS inhibitors have differential effect on stress responses and inhibition of NO could be responsible for the beneficial effect on regulation of stress.
authors.affiliation: Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, Banpo-dong, Seocho-gu, Seoul 137-701, Republic of Korea.
authors.forename: Hye-Young
authors.initials: HY
authors.lastname: Joung
authors.forename: Eun-Yee
authors.initials: EY
authors.lastname: Jung
authors.forename: Kyungsoo
authors.initials: K
authors.lastname: Kim
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Lee
authors.forename: Song
authors.initials: S
authors.lastname: Her
authors.forename: Insop
authors.initials: I
authors.lastname: Shim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000097:blood* / Q000188:drug therapy* / Q000209:etiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D003345:Corticosterone / Q000097:blood*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007191:Indazoles / Q000627:therapeutic use; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009249:NADP / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012149:Restraint, Physical / Q000009:adverse effects
chemical_list: D014151:Anti-Anxiety Agents; D007191:Indazoles; D009566:Nitrates; D009573:Nitrites; D009249:NADP; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole; D019331:NG-Nitroarginine Methyl Ester; D003345:Corticosterone