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The role of NMDA receptor and nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effect of dextromethorphan in mice forced swimming test and tail suspension test.
Biomed Pharmacother 2017; 85:627-634BP

Abstract

Depression is a devastating disorder which has a high impact on the wellbeing of overall society. As such, need for innovative therapeutic agents are always there. Most of the researchers focused on N-methyl-d-aspartate receptor to explore the antidepressant like activity of new therapeutic agents. Dextromethorphan is a cough suppressant agent with potential antidepressant activity reported in mouse force swimming test. Considering N-methyl-d-aspartate as a forefront in exploring antidepressant agents, here we focused to unpin the antidepressant mechanism of dextromethorphan targeting N-methyl-d-aspartate receptor induced nitric oxide-cyclic guanosine monophosphate signaling. Dextromethorphan administered at a dose of 10 and 30mg/kg i.p significantly reduced the immobility time. Interestingly, this effect of drug (30mg/kg) was inhibited when the animals were pretreated either with N-methyl-d-aspartate (75mg/kg), or l-arginine (750mg/kg) as a nitric oxide precursor and/or sildenafil (5mg/kg) as a phosphodiesterase 5 inhibitor. However, the antidepressant effect of Dextromethorphan subeffective dose (3mg/kg) was augmented when the animals were administered with either L-NG-Nitroarginine methyl ester (10mg/kg) non-specific nitric oxide synthase inhibitor, 7-Nitroindazole (30mg/kg) specific neural nitric oxide synthase inhibitor, MK-801 (0.05mg/kg) an N-methyl-d-aspartate receptor antagonist but not aminoguanidine (50mg/kg) which is specific inducible nitric oxide synthase inhibitor as compared to the drugs when administered alone. No remarkable effect on locomotor activity was observed during open field test when the drugs were administered at the above mentioned doses. Therefore, it is evident that the antidepressant like effect of Dextromethorphan is owed due to its inhibitory effect on N-methyl-d-aspartate receptor and NO- Cyclic guanosine monophosphate pathway.

Authors+Show Affiliations

Department of Neurology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Science, 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, International Campus, 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; Experimental Medicine Research Center, 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.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran; Department of Pharmacology, School of Medicine, AJA 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; 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. Electronic address: Dehpour@sina.tums.ac.ir.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27908707

Citation

Sakhaee, Ehsan, et al. "The Role of NMDA Receptor and Nitric Oxide/cyclic Guanosine Monophosphate Pathway in the Antidepressant-like Effect of Dextromethorphan in Mice Forced Swimming Test and Tail Suspension Test." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 85, 2017, pp. 627-634.
Sakhaee E, Ostadhadi S, Khan MI, et al. The role of NMDA receptor and nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effect of dextromethorphan in mice forced swimming test and tail suspension test. Biomed Pharmacother. 2017;85:627-634.
Sakhaee, E., Ostadhadi, S., Khan, M. I., Yousefi, F., Norouzi-Javidan, A., Akbarian, R., ... Dehpour, A. R. (2017). The role of NMDA receptor and nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effect of dextromethorphan in mice forced swimming test and tail suspension test. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 85, pp. 627-634. doi:10.1016/j.biopha.2016.11.073.
Sakhaee E, et al. The Role of NMDA Receptor and Nitric Oxide/cyclic Guanosine Monophosphate Pathway in the Antidepressant-like Effect of Dextromethorphan in Mice Forced Swimming Test and Tail Suspension Test. Biomed Pharmacother. 2017;85:627-634. PubMed PMID: 27908707.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of NMDA receptor and nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effect of dextromethorphan in mice forced swimming test and tail suspension test. AU - Sakhaee,Ehsan, AU - Ostadhadi,Sattar, AU - Khan,Muhammad Imran, AU - Yousefi,Farbod, AU - Norouzi-Javidan,Abbas, AU - Akbarian,Reyhaneh, AU - Chamanara,Mohsen, AU - Zolfaghari,Samira, AU - Dehpour,Ahmad-Reza, Y1 - 2016/11/28/ PY - 2016/08/04/received PY - 2016/10/29/revised PY - 2016/11/16/accepted PY - 2016/12/3/pubmed PY - 2017/2/9/medline PY - 2016/12/3/entrez KW - Depression KW - Dextromethorphan KW - Forced swimming test KW - Mice KW - NMDA KW - Nitric oxide KW - Tail suspension test SP - 627 EP - 634 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 85 N2 - Depression is a devastating disorder which has a high impact on the wellbeing of overall society. As such, need for innovative therapeutic agents are always there. Most of the researchers focused on N-methyl-d-aspartate receptor to explore the antidepressant like activity of new therapeutic agents. Dextromethorphan is a cough suppressant agent with potential antidepressant activity reported in mouse force swimming test. Considering N-methyl-d-aspartate as a forefront in exploring antidepressant agents, here we focused to unpin the antidepressant mechanism of dextromethorphan targeting N-methyl-d-aspartate receptor induced nitric oxide-cyclic guanosine monophosphate signaling. Dextromethorphan administered at a dose of 10 and 30mg/kg i.p significantly reduced the immobility time. Interestingly, this effect of drug (30mg/kg) was inhibited when the animals were pretreated either with N-methyl-d-aspartate (75mg/kg), or l-arginine (750mg/kg) as a nitric oxide precursor and/or sildenafil (5mg/kg) as a phosphodiesterase 5 inhibitor. However, the antidepressant effect of Dextromethorphan subeffective dose (3mg/kg) was augmented when the animals were administered with either L-NG-Nitroarginine methyl ester (10mg/kg) non-specific nitric oxide synthase inhibitor, 7-Nitroindazole (30mg/kg) specific neural nitric oxide synthase inhibitor, MK-801 (0.05mg/kg) an N-methyl-d-aspartate receptor antagonist but not aminoguanidine (50mg/kg) which is specific inducible nitric oxide synthase inhibitor as compared to the drugs when administered alone. No remarkable effect on locomotor activity was observed during open field test when the drugs were administered at the above mentioned doses. Therefore, it is evident that the antidepressant like effect of Dextromethorphan is owed due to its inhibitory effect on N-methyl-d-aspartate receptor and NO- Cyclic guanosine monophosphate pathway. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/27908707/The_role_of_NMDA_receptor_and_nitric_oxide/cyclic_guanosine_monophosphate_pathway_in_the_antidepressant_like_effect_of_dextromethorphan_in_mice_forced_swimming_test_and_tail_suspension_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)31212-4 DB - PRIME DP - Unbound Medicine ER -