Behavioral, biochemical and cellular correlates in the protective effect of sertraline against transient global ischemia induced behavioral despair: possible involvement of nitric oxide-cyclic guanosine monophosphate study pathway.
Post-stroke depression (PSD) is one of the psychiatric complications after stroke. Present study was conducted to elucidate the protective effect of sertraline and possible involvement of nitric oxide mechanism against transient global ischemia induced behavioral despair. Bilateral common carotid artery occlusion was given twice for 5 min at 10 min interval followed by 96 h reperfusion. Ischemia reperfusion significantly increased immobility period and decreased resistance to lateral push as compared to sham-operated group. Ischemia reperfusion caused significant oxidative damage and mitochondrial enzyme complex (I-III) dysfunction as compared to sham group. Sertraline (5 and 10mg/kg) treatment significantly reduced immobility period, increased resistance to lateral push, attenuated oxidative damage and restored mitochondrial enzyme complex activities as compared to ischemia group. L-Arginine (100mg/kg) or sildenafil (5mg/kg) pretreatment with sertraline (5mg/kg) significantly reversed the protective effect of sertraline. However, L-NAME (10mg/kg) or 7NI (10mg/kg) pretreatment with sertraline (5mg/kg) significantly potentiated their protective effect which were significant as compared to their effect alone. The present study shows that nitric oxide modulation is involved in the protective effect of sertraline.
Gaur
Vaibhav
V
Pharmacology Division, University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Study, Panjab University, Chandigarh 160014, India.
Kumar
Anil
A
D000328:Adult; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D006152:Cyclic GMP / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000378:metabolism; D006801:Humans; D002546:Ischemic Attack, Transient / Q000150:complications* / Q000503:physiopathology; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009483:Neuropsychological Tests; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000378:metabolism; D018384:Oxidative Stress; D011897:Random Allocation; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology; D020280:Sertraline / Q000494:pharmacology / Q000627:therapeutic use
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D006152:Cyclic GMP; D020280:Sertraline; D019331:NG-Nitroarginine Methyl Ester