7-Nitroindazole, a nitric oxide synthase inhibitor, has anxiolytic-like properties in exploratory models of anxiety

• Published in: Psychopharmacologia 1997-06, Vol.131 (4), p.399-405
• Main Authors: VOLKE, V, SOOSAAR, A, KOKS, S, BOURIN, M, MÄNNISTÖ, P. T, VASAR, E
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animal models; Animals; Anxiety; Anxiety - psychology; Anxiolytics; Arginine; Behavior, Animal - drug effects; Biological and medical sciences; Indazoles - pharmacology; Interpersonal Relations; Male; Medical sciences; Mice; Motor Activity - drug effects; Neuropharmacology; Neuroprotective Agents - pharmacology; Nitric oxide; Nitric Oxide - physiology; Nitric Oxide Synthase - antagonists & inhibitors; Nitric-oxide synthase; Open-field behavior; Pharmacology. Drug treatments; Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Social interaction
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050309

The action of the novel nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI) was studied in different exploratory models of anxiety. In the rat plus-maze test, 7-NI potently increased time spent on open arms and percentage of open arm visits in a dose dependent manner with the minimal effective dose of 40 mg/kg. 7-NI caused an anxiolytic-like effect in the rat social interaction test. The minimal dose increasing social interaction time was 20 mg/kg. However, the drug also produced a clear sedative effect occurring even at smaller doses (10 mg/kg) in the open field test. 7-NI also showed an anxiolytic-like profile in the mouse light-dark compartment test and in the elevated plus-maze test, but the doses required were higher (80-120 mg/kg) than in rat models. Also, the sedative effect occurred at these doses in open field. We failed to demonstrate any effect of L-arginine either in the rat elevated plus-maze test or in the open field test at doses up to 600 mg/kg IP. These results indicate that there are no major interspecies differences between rats and mice in respect of action of 7-NI. The clear anxiolytic-like action of the nitric oxide synthase inhibitor in four different models shows that nitric oxide is involved in the process of anxiety and that NOS could be a new target in developing anxiolytic drugs.