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Antagonism of nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration procedure by pharmacologic disruption of endogenous nitric oxide function

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Abstract

Rationale

Previous studies have shown the anxiolytic-like effects of nitrous oxide (N2O) to be sensitive to antagonism by non-specific inhibitors of nitric oxide synthase (NOS).

Objectives

The present study was conducted to demonstrate further the involvement of nitric oxide (NO) and ascertain whether a specific isoform of NOS is involved in N2O-induced behavior in mice.

Methods

Male NIH Swiss mice were tested in the light/dark exploration test to determine how N2O-induced behavior was affected by the following pretreatments: the NO scavenger hemoglobin (Hb); the selective nNOS-inhibitor S-methyl-l-thiocitrulline (SMTC); the selective eNOS-inhibitor N(5)-(1-iminoethyl)-l-ornithine (l-NIO); and the selective iNOS-inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine (AMT). Furthermore, NOS activity was assessed in the whole brain as well as five brain areas of N2O- versus room air-exposed mice to determine the effects of N2O on NOS activity.

Results

The behavioral effects of N2O in the light/dark exploration test were significantly attenuated following pretreatment with Hb (2.0 nmol, i.c.v.), SMTC (0.3 µg and 1.0 µg per mouse, i.c.v.) and the higher dose of l-NIO (30 mg/kg, s.c.). However, the N2O-induced behavioral effect was unaltered by pretreatment with either the lower dose of l-NIO (10 mg/kg, s.c.) or AMT (1.0 mg/kg and 3.0 mg/kg, s.c.). Finally exposure to 50% N2O for 15 min significantly increased NOS activity in the cerebellum and corpus striatum but not in other brain regions or whole brain.

Conclusion

These findings provide further support for the hypothesis that NO is involved in N2O-induced anxiolytic-like behavior and that this NO is the product of nNOS enzyme activity.

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Acknowledgement

This work was support by NIH grant DA-10343.

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, P.O. Box 646534, Pullman, WA 99164-6534, USA

    Shuang Li, Yusuke Ohgami & Raymond M. Quock

  2. Graduate Program in Pharmacology and Toxicology, Washington State University, Pullman, WA, USA

    Shuang Li & Raymond M. Quock

  3. Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA

    Yang Dai

  4. Department of School-Nursing, Kyushu Women's Junior College, Fukuoka, Japan

    Yusuke Ohgami

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  1. Shuang Li
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  2. Yusuke Ohgami
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Correspondence to Raymond M. Quock.

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Li, S., Ohgami, Y., Dai, Y. et al. Antagonism of nitrous oxide-induced anxiolytic-like behavior in the mouse light/dark exploration procedure by pharmacologic disruption of endogenous nitric oxide function. Psychopharmacology 166, 366–372 (2003). https://doi.org/10.1007/s00213-002-1363-0

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  • DOI: https://doi.org/10.1007/s00213-002-1363-0

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