Shuang Li Yusuke Ohgami Yang Dai Raymond M. Quock +1-509-3355956 +1-509-3355902 email@example.com Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, P.O. Box 646534, Pullman, WA 99164-6534, USA Graduate Program in Pharmacology and Toxicology, Washington State University, Pullman, WA, USA Department of Pharmaceutics, School of Pharmacy, University of Washington, Seattle, WA, USA Department of School-Nursing, Kyushu Women's Junior College, Fukuoka, Japan Rationale. Previous studies have shown the anxiolytic-like effects of nitrous oxide (N 2 O) 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 N 2 O-induced behavior in mice. Methods. Male NIH Swiss mice were tested in the light/dark exploration test to determine how N 2 O-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 N 2 O- versus room air-exposed mice to determine the effects of N 2 O on NOS activity. Results. The behavioral effects of N 2 O 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 N 2 O-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% N 2 O 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 N 2 O-induced anxiolytic-like behavior and that this NO is the product of nNOS enzyme activity.
Psychopharmacology – Springer Journals
Published: Apr 1, 2003
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