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Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test.
Biomed Pharmacother 2016; 82:713-21BP

Abstract

Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (P<0.01) without any effect on locomotor activity in the open-field test (OFT), while higher dose of lamotrigine (30mg/kg) reduced the immobility time in the FST (P<0.001) as well as the number of crossings in the OFT. Pretreatment of animals with NMDA (75mg/kg), l-arginine (750mg/kg, a substrate for nitric oxide synthase [NOS]) or sildenafil (5mg/kg, a phosphodiesterase [PDE] 5 inhibitor) reversed the antidepressant-like effect of lamotrigine (10mg/kg) in the FST. Injection of l-nitroarginine methyl ester (l-NAME, 10mg/kg, a non-specific NOS inhibitor), 7-nitroindazole (30mg/kg, a neuronal NOS inhibitor), methylene blue (20mg/kg, an inhibitor of both NOS and soluble guanylate cyclase [sGC]), or MK-801 (0.05mg/kg), ketamine (1mg/kg), and magnesium sulfate (10mg/kg) as NMDA receptor antagonists in combination with a sub-effective dose of lamotrigine (5mg/kg) diminished the immobility time of animals in the FST compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the OFT. Based on our findings, it is suggested that the antidepressant-like effect of lamotrigine might mediated through inhibition of either NMDA receptors or NO-cGMP synthesis.

Authors+Show Affiliations

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 and Therapeutics, National University of Ireland, Galway, Ireland.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran.Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Experimental Medicine Research Center, 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.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; Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address: Dehpour@sina.tums.ac.ir.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27470415

Citation

Ostadhadi, Sattar, et al. "Pharmacological Evidence for the Involvement of the NMDA Receptor and Nitric Oxide Pathway in the Antidepressant-like Effect of Lamotrigine in the Mouse Forced Swimming Test." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 82, 2016, pp. 713-21.
Ostadhadi S, Ahangari M, Nikoui V, et al. Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test. Biomed Pharmacother. 2016;82:713-21.
Ostadhadi, S., Ahangari, M., Nikoui, V., Norouzi-Javidan, A., Zolfaghari, S., Jazaeri, F., ... Dehpour, A. R. (2016). Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 82, pp. 713-21. doi:10.1016/j.biopha.2016.05.035.
Ostadhadi S, et al. Pharmacological Evidence for the Involvement of the NMDA Receptor and Nitric Oxide Pathway in the Antidepressant-like Effect of Lamotrigine in the Mouse Forced Swimming Test. Biomed Pharmacother. 2016;82:713-21. PubMed PMID: 27470415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test. AU - Ostadhadi,Sattar, AU - Ahangari,Mohammad, AU - Nikoui,Vahid, AU - Norouzi-Javidan,Abbas, AU - Zolfaghari,Samira, AU - Jazaeri,Farahnaz, AU - Chamanara,Mohsen, AU - Akbarian,Reyhaneh, AU - Dehpour,Ahmad-Reza, Y1 - 2016/06/14/ PY - 2016/04/26/received PY - 2016/05/23/accepted PY - 2016/7/30/entrez PY - 2016/7/30/pubmed PY - 2017/2/9/medline KW - Depression KW - Forced swimming test KW - Lamotrigine KW - Mice KW - NMDA KW - Nitric oxide SP - 713 EP - 21 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 82 N2 - Lamotrigine is an anticonvulsant agent that shows clinical antidepressant properties. The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) receptors and nitric oxide-cyclic guanosine monophosphate (NO-cGMP) synthesis in possible antidepressant-like effect of lamotrigine in forced swimming test (FST) in mice. Intraperitoneal administration of lamotrigine (10mg/kg) decreased the immobility time in the FST (P<0.01) without any effect on locomotor activity in the open-field test (OFT), while higher dose of lamotrigine (30mg/kg) reduced the immobility time in the FST (P<0.001) as well as the number of crossings in the OFT. Pretreatment of animals with NMDA (75mg/kg), l-arginine (750mg/kg, a substrate for nitric oxide synthase [NOS]) or sildenafil (5mg/kg, a phosphodiesterase [PDE] 5 inhibitor) reversed the antidepressant-like effect of lamotrigine (10mg/kg) in the FST. Injection of l-nitroarginine methyl ester (l-NAME, 10mg/kg, a non-specific NOS inhibitor), 7-nitroindazole (30mg/kg, a neuronal NOS inhibitor), methylene blue (20mg/kg, an inhibitor of both NOS and soluble guanylate cyclase [sGC]), or MK-801 (0.05mg/kg), ketamine (1mg/kg), and magnesium sulfate (10mg/kg) as NMDA receptor antagonists in combination with a sub-effective dose of lamotrigine (5mg/kg) diminished the immobility time of animals in the FST compared with either drug alone. None of the drugs produced significant effects on the locomotor activity in the OFT. Based on our findings, it is suggested that the antidepressant-like effect of lamotrigine might mediated through inhibition of either NMDA receptors or NO-cGMP synthesis. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/27470415/Pharmacological_evidence_for_the_involvement_of_the_NMDA_receptor_and_nitric_oxide_pathway_in_the_antidepressant_like_effect_of_lamotrigine_in_the_mouse_forced_swimming_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)30560-1 DB - PRIME DP - Unbound Medicine ER -