A role of nitric oxide mechanism involved in the protective effects of venlafaxine in sleep deprivation.
The present study was designed to explore the possible nitric oxide mechanism in protective effect of venlafaxine in sleep deprivation in mice. Laca mice were sleep deprived for period of 72 h using grid suspended over water method. Venlafaxine (2.5, 5 and 10mg/kg, ip), l-arginine (50mg/kg, ip), l-NAME (10mg/kg, ip) and methylene blue (10mg/kg, ip) were administered for 5 days, starting 2 days before 72-h sleep deprivation. Various behavioral tests (plus maze, zero maze, mirror chamber tests for anxiety, and actophotometer test) followed by oxidative stress parameters (malondialdehyde level, glutathione, catalase, nitrite and protein) were assessed. The present study showed that venlafaxine (5 and 10mg/kg, ip) drug treatment significantly reversed 72-h sleep deprivation caused anxiety like behavior, impairment in locomotor activity and oxidative damage (increased lipid peroxidation and nitrite levels and depleted reduced glutathione and catalase activity) as compared to control. l-NAME (10mg/kg) and methylene blue (10mg/kg) pretreatment with lower dose of venlafaxine (5mg/kg) potentiated the protective effect of venlafaxine (5mg/kg). However, l-arginine (50mg/kg) pretreatment with venlafaxine (5mg/kg) reversed the protective effect of venlafaxine. Results of present study suggest that nitric oxide mechanism is involved in the protective effect of venlafaxine against sleep-deprivation-induced behavior alteration and oxidative damage in mice.
Kumar
Anil
A
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India. kumaruips@yahoo.com
Garg
Ruchika
R
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage*; D001007:Anxiety / Q000209:etiology / Q000517:prevention & control*; D001120:Arginine / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D003511:Cyclohexanols / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D015227:Lipid Peroxidation / Q000187:drug effects; D018782:Maze Learning / Q000187:drug effects; D008751:Methylene Blue / Q000008:administration & dosage; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000378:metabolism; D011930:Reaction Time / Q000187:drug effects; D012892:Sleep Deprivation / Q000150:complications* / Q000188:drug therapy; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D003511:Cyclohexanols; D004791:Enzyme Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D000069470:Venlafaxine Hydrochloride; D001120:Arginine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester