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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.
Brain Res Bull 2016; 122:62-70BR

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+Show Affiliations

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.Department of Pharmacology, School of Medicine, International Campus, Tehran University of Medical Sciences, Tehran, Iran.Brain and Spinal Cord Injury Research Center, Neuroscience Institute Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.Department of Tissue Engineering and Applied Cell Sciences Iran University of Medical Sciences, Tehran, Iran.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26988103

Citation

Ostadhadi, Sattar, et al. "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." Brain Research Bulletin, vol. 122, 2016, pp. 62-70.
Ostadhadi S, Khan MI, Norouzi-Javidan A, et al. 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. Brain Res Bull. 2016;122:62-70.
Ostadhadi, S., Khan, M. I., Norouzi-Javidan, A., Chamanara, M., Jazaeri, F., Zolfaghari, S., & Dehpour, A. R. (2016). 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. Brain Research Bulletin, 122, pp. 62-70. doi:10.1016/j.brainresbull.2016.03.004.
Ostadhadi S, et al. 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. Brain Res Bull. 2016;122:62-70. PubMed PMID: 26988103.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Ostadhadi,Sattar, AU - Khan,Muhammad Imran, AU - Norouzi-Javidan,Abbas, AU - Chamanara,Mohsen, AU - Jazaeri,Farahnaz, AU - Zolfaghari,Samira, AU - Dehpour,Ahmad-Reza, Y1 - 2016/03/14/ PY - 2015/12/03/received PY - 2016/03/06/revised PY - 2016/03/11/accepted PY - 2016/3/19/entrez PY - 2016/3/19/pubmed PY - 2017/1/6/medline KW - Depression KW - Forced swimming test KW - Mice KW - NMDA KW - Nitric oxide KW - Topiramate SP - 62 EP - 70 JF - Brain research bulletin JO - Brain Res. Bull. VL - 122 N2 - 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. SN - 1873-2747 UR - https://www.unboundmedicine.com/medline/citation/26988103/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0361-9230(16)30047-8 DB - PRIME DP - Unbound Medicine ER -