title: Differential neuromodulatory role of NO in anxiety and seizures: an experimental study.
abstract: Nitric oxide is a simple, ubiquitous, diatomic molecule with complex neuromodulatory functions. Anxiety and seizures are closely similar neurobehavioral disorders and are regulated by limbic system. The present study evaluated the regulatory roles of NO in these pathophysiological states in experimental models. In test for anxiety, aminophylline induced anxiogenic responses were assessed by the elevated plus maze (EPM) test, and a low dose of the drug (50 mg/kg) reduced both open arm entries and open arm time in rats. Pretreatment with the NO mimetic, L-arginine (500 and 1000 mg/kg) and melatonin (50 mg/kg) attenuated aminophylline induced anxiogenesis whereas the NO synthase inhibitors, L-NAME and 7-NI (30 mg/kg) aggravated the anxiogeneic response. Such aminophylline induced neurobehavioral suppression in the EPM activity was accompanied by increases in MDA levels and reductions in GSH and NOx activity in brain homogenates - changes which were reversed by L-arginine and melatonin pretreatments. In tests for seizures, aminophylline induced seizures and mortality at higher dose levels of the drug (300 mg/kg). Interestingly, such seizures and mortality in rats were antagonized by L-NAME and 7-NI pretreatments. On the other hand, L-arginine tended to potentiate seizures after sub-convulsive dose (100 mg/kg) of this methylxanthine. Aminophylline induced seizures were accompanied by greater elevations in brain MDA levels, whereas, GSH levels were consistently lowered. Unlike that seen during anxiety, NOx levels were increased in brain homogenates of these rats. The changes in oxidative stress markers were neutralized by NO synthase inhibitors. Synergistic anticonvulsant effect on aminophylline seizures was seen when L-NAME was combined with melatonin. These pharmacological and biochemical data indicate that aminophylline induced anxiety and seizures are differentially modulated by NO.
authors.affiliation: Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110 007, India. Electronic address: kavgul2002@yahoo.com.
authors.forename: Kavita
authors.initials: K
authors.lastname: Gulati
authors.affiliation: Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110 007, India.
authors.forename: Arunabha
authors.initials: A
authors.lastname: Ray
mesh_terms: D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D001120:Arginine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008550:Melatonin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures
chemical_list: D004791:Enzyme Inhibitors; D018377:Neurotransmitter Agents; D000628:Aminophylline; D009569:Nitric Oxide; D008315:Malondialdehyde; D001120:Arginine; D008550:Melatonin; D019331:NG-Nitroarginine Methyl Ester
keywords: Anxiety; L-NAME; L-arginine; Melatonin; Nitric oxide; Seizures