Differential effects of nitric oxide synthase inhibitors on anxiety in unstressed and stressed mice.
Effects of selective nitric oxide synthase (NOS) inhibitors, 7-nitroindazole (7-NI), a selective inhibitor of neuronal nitric oxide synthase (nNOS) and aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on anxiety in unstressed and stressed mice were investigated using elevated plus maze (EPM) test and light-dark test (LDT). 7-NI (20 and 40 mg/kg, ip) produced anti-anxiety effect in unstressed mice but not in stressed mice. AG (50 and 100 mg/kg, ip) produced anxiolytic effect in stressed mice and failed to produce the similar effect in unstressed mice. Nitrite levels were increased in stressed mice, but not in unstressed mice, exposed to EPM and LDT for 5 min. Increased nitrite levels in stressed mice were attenuated by AG, but not by 7-NI. The effects of AG were enhanced by pyrrolidine-dithio-carbamate (PDTC), an inhibitor of NF-kappaB induction, in stressed mice. The results suggest the possible role of inducible nitric oxide synthase in stress-induced anxiogenesis as compared to unstressed mice, where neuronal form of NOS may plays predominant role.
Gilhotra
Neeraj
N
Pharmacology Division, Department of Pharmaceutical Sciences, Guru Jambheshwar University of Science and Technology, Hisar 125 001, India. neeraj_gilhotra@yahoo.co.in
Jain
Harshita
H
Dhingra
Dinesh
D
D000818:Animals; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D003624:Darkness; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007191:Indazoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008027:Light; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D009573:Nitrites / Q000097:blood; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology / Q000503:physiopathology; D013859:Thiocarbamates / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use
D014151:Anti-Anxiety Agents; D004791:Enzyme Inhibitors; D006146:Guanidines; D007191:Indazoles; D009573:Nitrites; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496321:Nos1 protein, mouse; C496317:Nos2 protein, mouse; C004479:pimagedine; C080122:7-nitroindazole