The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic efficacy without tolerance in rats following subchronic administration

The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic efficacy without... The nitric oxide synthase inhibitor 7-nitroindazole (7-NI) dose-dependently (3.0–30.0 mg/kg) displayed anxiolytic activity, as measured by an increase in open arm exploration time in the elevated plus-maze (EPM), following intraperitoneal (i.p.) administration in rats. Acute administration of 7-NI at 30.0 mg/kg significantly ( P <0.05) increased open arm exploration time by 176% compared to vehicle control, similar to the benzodiazepine diazepam at 1.0 and 3.0 mg/kg (+191 and +200%, respectively). However, 39 h following subchronic 5-day administration of diazepam twice daily (bid) at 3.0 mg/kg, diazepam was devoid of anxiolytic activity at 1.0 mg/kg, as measured by no difference in open arm exploration time compared to vehicle control, while the 3.0 mg/kg dose still produced a significant ( P <0.05) 175% increase in open arm exploration time. In contrast, following subchronic administration of 7-NI (30.0 mg/kg, bid), a significant ( P <0.01) enhancement in open arm exploration time was observed at 30.0 mg/kg (+665% compared to control). Therefore, inhibition of nitric oxide synthase by 7-NI resulted in anxiolysis similar to diazepam following acute administration in the EPM. However, following subchronic administration, unlike diazepam which showed an attenuation of anxiolytic activity, 7-NI displayed enhanced anxiolytic efficacy and was devoid of tolerance. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Neuropharmacology Elsevier

The nitric oxide synthase inhibitor 7-nitroindazole displays enhanced anxiolytic efficacy without tolerance in rats following subchronic administration

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Publisher
Elsevier
Copyright
Copyright © 1998 Elsevier Science Ltd
ISSN
0028-3908
eISSN
1873-7064
DOI
10.1016/S0028-3908(98)00076-8
Publisher site
See Article on Publisher Site

Abstract

The nitric oxide synthase inhibitor 7-nitroindazole (7-NI) dose-dependently (3.0–30.0 mg/kg) displayed anxiolytic activity, as measured by an increase in open arm exploration time in the elevated plus-maze (EPM), following intraperitoneal (i.p.) administration in rats. Acute administration of 7-NI at 30.0 mg/kg significantly ( P <0.05) increased open arm exploration time by 176% compared to vehicle control, similar to the benzodiazepine diazepam at 1.0 and 3.0 mg/kg (+191 and +200%, respectively). However, 39 h following subchronic 5-day administration of diazepam twice daily (bid) at 3.0 mg/kg, diazepam was devoid of anxiolytic activity at 1.0 mg/kg, as measured by no difference in open arm exploration time compared to vehicle control, while the 3.0 mg/kg dose still produced a significant ( P <0.05) 175% increase in open arm exploration time. In contrast, following subchronic administration of 7-NI (30.0 mg/kg, bid), a significant ( P <0.01) enhancement in open arm exploration time was observed at 30.0 mg/kg (+665% compared to control). Therefore, inhibition of nitric oxide synthase by 7-NI resulted in anxiolysis similar to diazepam following acute administration in the EPM. However, following subchronic administration, unlike diazepam which showed an attenuation of anxiolytic activity, 7-NI displayed enhanced anxiolytic efficacy and was devoid of tolerance.

Journal

NeuropharmacologyElsevier

Published: Jul 1, 1998

References

  • Inhibition of nitric oxide synthase-potential for a novel class of therapeutic agent?
    Ogden, J.E.; Moore, P.K.
  • Nitric oxide synthase inhibition does not impair visual or spatial discrimination learning
    Tobin, J.R.; Gorman, L.K.; Baxter, M.G.; Traystman, R.J.
  • 7-Nitroindazole, a nitric oxide synthase inhibitor, has anxiolytic-like properties in exploratory models of anxiety
    Volke, V.; Soosaar, A.; Koks, S.; Bourin, M.; Mannisto, P.T.; Vasar, E.

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