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


OBJECTIVE
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 micro g and 1.0 micro g 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.


CONCLUSIONS
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.
Li
Shuang
S
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, PO Box 646534, Pullman, WA 99164-6534, USA.
Ohgami
Yusuke
Y
Dai
Yang
Y
Quock
Raymond M
RM
D018685:Anesthetics, Inhalation; D000818:Animals; D001007:Anxiety / Q000139:chemically induced*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005106:Exploratory Behavior / Q000187:drug effects*; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009609:Nitrous Oxide / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017440:Photoperiod; D051381:Rats
D018685:Anesthetics, Inhalation; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D009609:Nitrous Oxide