title: Possible role of nitric oxide (NO) in the regulation of gender related differences in stress induced anxiogenesis in rats.
abstract: Gender related differences in stress induced neurobehavioral disorders have been reported although the mechanisms involved are not yet clear. The present study investigated the role of nitric oxide, an important biomodulator in the sex related differences in stress induced anxiety like behavior in rats. Restraint stress (RS for 1 h) was used as the experimental stressor and the effects of NO modulators were assessed in the elevated plus maze (EPM) test in both male and female rats. No metabolites (NOx) and asymmetric dimethyl arginine (ADMA) were measured in brain homogenates of these rats for corroborative purposes. RS induced anxiogenesis in both male and female rats and such changes were greater in males as compared to females. The behavioral alterations were associated with enhanced levels of ADMA and reductions in levels of NOx in brain homogenates - the effects being greater in intensity in males as compared to females. Pretreatment with NO precursor L-arginine (500 mg/kg) reversed the RS induced behavioral and biochemical changes, while NO synthase inhibitor L-NAME (50 mg/kg) had opposite effects. Additionally, Formestane (50 mg/kg), an estrogen synthesis blocker, aggravated stress induced anxiogenesis with a corresponding increase in ADMA and decrease in NOx levels in the females. To our knowledge, this is the first report indicating the involvement of ADMA, an endogenous nitric oxide synthase inhibitor in stress induced neurobehavioral changes. Furthermore, it is also evident that nitric oxide and its interactions with estrogens play a crucial modulatory role in the differential anxiogenic response to stress among males and females.
authors.affiliation: Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.
authors.forename: Ayanabha
authors.initials: A
authors.lastname: Chakraborti
authors.affiliation: Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India. Electronic address: kavgul2002@gmail.com.
authors.forename: Kavita
authors.initials: K
authors.lastname: Gulati
authors.affiliation: Department of Pharmacology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.
authors.forename: Arunabha
authors.initials: A
authors.lastname: Ray
mesh_terms: D000735:Androstenedione / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors; D013312:Stress, Physiological / Q000187:drug effects
chemical_list: D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D000735:Androstenedione; C018524:N,N-dimethylarginine; D001120:Arginine; C014594:formestane; D019331:NG-Nitroarginine Methyl Ester
keywords: Anxiety; Estrogen; Gender difference; Nitric oxide; Stress