Behavioral effects of 7-nitroindazole on hyperbaric oxygen toxicity.
The aim of this study was to evaluate the role of nitric oxide (NO) upon hyperbaric oxygen (HBO) toxicity in male Sprague-Dawley rats during exposure to 0.5 MPa >99% O(2). In the first experiment, the selective neuronal NO synthase inhibitor 7-nitroindazole (7-NI) was injected intraperitoneally (ip) in 15 rats. Another 15 rats received vehicle injections of peanut oil intraperitoneally. Latency to observable tonic-clonic convulsions and motor activity during the HBO exposure were scored and compared between the control group and the 7-NI group. The results showed that injection of 7-NI (30 mg/kg) significantly prolonged the latency to observable tonic-clonic convulsions. The 7-NI group also showed a significant decrease in motor activity compared with the control group. A second experiment was performed to measure the effect of 7-NI injections upon open-field activity during normobaric conditions. Twenty-four male Sprague-Dawley rats were randomly divided into three groups, each consisting of eight rats receiving 30 mg/kg 7-NI injections, 10 mg/kg 7-NI injections or vehicle injections of peanut oil intraperitoneally, respectively. The results showed that injection of 7-NI led to a significant dose-dependent reduction in horizontal and vertical activities. This study shows that 7-NI prolongs the latency to hyperoxia-induced seizures. However, it also demonstrates that 7-NI in doses ranging from 30 to 10 mg/kg has a secondary effect upon motor behavior in general. It can therefore not be ruled out that the protective effect of 7-NI upon HBO intoxication is partly due to reduced motor activity.
Division of Physiological Psychology, Department of Biological and Medical Psychology, University of Bergen, Aarstadvn. 21, N-5009 Bergen, Norway. jellestad@psych.uib.no
Finn Konow
FK
Jellestad
Hilde
H
Gundersen
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004830:Epilepsy, Tonic-Clonic / Q000139:chemically induced; D006931:Hyperbaric Oxygenation / Q000009:adverse effects*; D007191:Indazoles / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D052248:Nitric Oxide Synthase Type I; D010100:Oxygen / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007191:Indazoles; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D010100:Oxygen; C080122:7-nitroindazole