Venlafaxine involves nitric oxide modulatory mechanism in experimental model of chronic behavior despair in mice.
Present study has been designed to elucidate the nitric oxide modulatory mechanism of venlafaxine in experimental model of chronic behavior despair in mice. Animals (male albino laca mice) were forced to swim daily for 6 min test session for 7 days and immobility period of each animal was measured on every alternate days. Six minutes forced swimming test session for 7 days caused anxiety-like behavior (as assessed by mirror chamber and plus maze tests) and impairment in locomotor activity followed by oxidative damage (increased lipid peroxidation, nitrite concentration, depleted reduced glutathione and catalase activity) as compared to naïve animals. Seven days venlafaxine (5 and 10 mg/kg) treatment significantly caused anti-anxiety-like effect, improved locomotor activity and attenuated oxidative damage (reduced lipid peroxidation, nitrite concentration and caused restoration of reduce glutathione and catalase activity) as compared to control. Caffeine (10 mg/kg) pretreatment with venlfaxine (5 mg/kg) did not produce any significant effect on locomotor activity, immobility period and oxidative damage as compared to their effect per se. Further, L-NAME (5 mg/kg) and methylene blue (10 mg/kg) pretreatment with sub effective dose of venlafaxine (5 mg/kg) potentiated its protective effect which was significant as compared to their effect per se. However, L-arginine (100 mg/kg) pretreatment with venlafaxine (5 mg/kg) significantly reversed the protective effect of venlafaxine (P<0.05). Present study suggests that nitric oxide modulation might be involved in the protective effects of venlafaxine.
Kumar
Anil
A
Pharmacology division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh, India. kumaruips@yahoo.com
Garg
Ruchika
R
Gaur
Vaibhav
V
Kumar
Puneet
P
D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000008:administration & dosage / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001120:Arginine / Q000378:metabolism; D002110:Caffeine / Q000008:administration & dosage / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology; D002908:Chronic Disease / Q000188:drug therapy; D003511:Cyclohexanols / Q000008:administration & dosage / Q000494:pharmacology*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D013550:Swimming; D000069470:Venlafaxine Hydrochloride
D018687:Antidepressive Agents, Second-Generation; D000697:Central Nervous System Stimulants; D003511:Cyclohexanols; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D002110:Caffeine; D000069470:Venlafaxine Hydrochloride; D001120:Arginine; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester