title: Involvement of NMDA receptors and L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test.
abstract: Topiramate (TPM) is an agent primarily used in the treatment of epilepsy. Using mice model of forced swimming test (FST) the current study was basically aimed to investigate the influence of TPM on depression by inhibiting NMDA receptor and nitric oxide-cGMP production. When TPM was administered in a dose of 20 and 30 mg/kg by i.p. route it reduced the immobility time during FST. However this effect of TPM (30 mg/kg, i.p.) in the FST was abolished when the mice were pretreated either with NMDA (75 mg/kg, i.p.), or l-arginine (750 mg/kg, i.p. NO precursor), or sildenafil (5mg/kg, i.p. Phosphodiesterase 5 inhibitor). The immobility time in the FST was reduced after administration of L-NAME (10mg/kg, i.p, a non-specific NOS inhibitor), 7-nitoinidazol (30 mg/kg, i.p. a nNOS inhibitor) or MK-801 (0.05 mg/kg, i.p, a NMDA receptor antagonist) in combination with a subeffective dose of TPM (10mg/kg, i.p.) as compared with single use of either drug. Co-administrated of lower doses of MK-801 (0.01 mg/kg) or L-NAME (1mg/kg) failed to effect immobility time. However, simultaneous administration of these two agents in the same doses with subeffective dose of TPM (10mg/kg, i.p.), reduced the immobility time during FST. None of these drugs were found to have a profound effect on the locomotor activity per se during the open field test. Taken together, our data demonstrates that TPM exhibit antidepressant-like effect which is accomplished either due to inhibition of NMDA receptors or NO-cGMP production.
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Sattar
authors.initials: S
authors.lastname: Ostadhadi
authors.affiliation: Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Muhammad Imran
authors.initials: MI
authors.lastname: Khan
authors.affiliation: Brain and Spinal Cord Injury Research Center, Neuroscience Institute Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Abbas
authors.initials: A
authors.lastname: Norouzi-Javidan
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Chamanara
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Farahnaz
authors.initials: F
authors.lastname: Jazaeri
authors.affiliation: Department of Tissue Engineering and Applied Cell Sciences Iran University of Medical Sciences, Tehran, Iran.
authors.forename: Samira
authors.initials: S
authors.lastname: Zolfaghari
authors.affiliation: Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Brain and Spinal Cord Injury Research Center, Neuroscience Institute Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: dehpour@yahoo.com.
authors.forename: Ahmad-Reza
authors.initials: AR
authors.lastname: Dehpour
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D001120:Arginine / Q000378:metabolism*; D001522:Behavior, Animal / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology; D019417:Hindlimb Suspension; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction; D013550:Swimming; D000077236:Topiramate
chemical_list: D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D016194:Receptors, N-Methyl-D-Aspartate; D000077236:Topiramate; D005632:Fructose; D009569:Nitric Oxide; D001120:Arginine; D006152:Cyclic GMP
keywords: Depression; Forced swimming test; Mice; NMDA; Nitric oxide; Topiramate