Effect of Withania somnifera Dunal Root Extract on Behavioral Despair Model in Mice: a Possible Role for Nitric Oxide.
Withania somnifera (WS) possess anti-inflammatory and antioxidant properties. WS preparations have a potential therapeutic role in the central nervous system (CNS) related disorders in animal models. In this study, the possible protective effect of acute aqueous WS root extract on behavioral despair was explored and compared with fluoxetine, an antidepressant with selective serotonin (5-HT) reuptake inhibitor activity (SSRI). Further, the probable involvement of nitric oxide (NO) determined to measure immobility time in forced swimming test (FST) and tail suspension test (TST) in male mice. Immediately after assessment of locomotor activity, the immobility time was evaluated. WS was administered intraperitoneally (200, 400 mg/kg; i.p.) 60 min before the behavioral tests. To assess the involvement of NO in the possible protective effect of WS, a non-specific NO synthase inhibitor, NG-L-arginine methyl ester (L-NAME, 10 mg/kg, i.p.) was administered 30 min before the extract administration (400 mg/kg, i.p.), 90 min before the tests. Acute WS extract (200, 400 mg/kg, i.p.) dose-dependently decreased the immobility time in FST, P<0.05, P<0.001, respectively and 400 mg/kg proved the most effective dose and this dose was comparable to fluoxetine (20 mg/kg, i.p. WS (400 mg/kg, i.p.) also lowered the immobility measure in TST (P<0.05). However, these effects were not related to change in locomotor activity. Moreover, L-NAME (10 mg/kg, i.p.) did not influence the effect of the extract on the behavioral tests. As a consequence, the immobility time was virtually constant between the group received the extract (400 mg/kg) alone, and the group received L-NAME (10 mg/kg) before the extract. It is probable that NO does not mediate this beneficial effect, and WS may affect other neurochemical systems and pathways.
Department of Biology, Islamic Azad University, Qom Branch, Qom, Iran. AND Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Mahshid
M
Attari
Department of Biology, Islamic Azad University, Qom Branch, Qom, Iran.
Fatemeh
F
Jamaloo
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Sahar
S
Shadvar
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Nahid
N
Fakhraei
Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.
Ahmad Reza
AR
Dehpour
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D013550:Swimming; D032341:Withania / Q000737:chemistry*
D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D010936:Plant Extracts; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester
Forced swimming test; Nitric oxide; Open field test; Tail suspension test; Withania somnifera