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The role of nitric oxide-cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test.
Pharmacol Rep 2018; 70(5):1015-1022PR

Abstract

BACKGROUND

Considering the pivotal role of nitric oxide (NO) pathway in depressive disorders, the aim of the present study was to investigate the antidepressant-like effect of selegiline in mice forced swimming test (FST), and possible involvement of NO-cyclic guanosine monophosphate (cGMP) pathway in this action.

METHODS

After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4min was evaluated. All drugs were given intraperitoneally (ip).

RESULTS

Selegiline (10mg/kg) decreased the immobility time in the FST similar to fluoxetine (20mg/kg). Pretreatment with l-arginine (NO precursor, 750mg/kg) or sildenafil (a phosphodiesterase 5 inhibitor, 5mg/kg) significantly reversed the selegiline anti-immobility effect. Sub-effective dose of selegiline (1mg/kg) showed a synergistic antidepressant effect with NG-nitro-l-arginine methyl ester (L-NAME, inhibitor of NO synthase, 10mg/kg) or 7-nitroindazole (specific neuronal NO synthase inhibitor, 30mg/kg), but not with aminoguanidine (specific inducible NO synthase inhibitor, 50mg/kg). Pretreatment of mice with methylene blue (an inhibitor of NO synthase and soluble guanylyl cyclase, 10mg/kg) significantly produced a synergistic response with the sub-effective dose of selegiline. Neither of the drugs changed the locomotor activity. Also, hippocampal and prefrontal cortex (PFC) nitrite content was significantly lower in selegiline-injected mice compared to saline-administrated mice. Also, co-injection of 7-nitroindazole with selegiline produced a significant reduction in hippocampal or PFC nitrite contents.

CONCLUSIONS

It is concluded that selegiline possesses antidepressant-like effect in mice FST through inhibition of l-arginine-NO-cyclic guanosine monophosphate pathway.

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; 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.Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.Razi Drug Research Center, Iran 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, 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

30144662

Citation

Ostadhadi, Sattar, et al. "The Role of Nitric oxide-cGMP Pathway in Selegiline Antidepressant-like Effect in the Mice Forced Swim Test." Pharmacological Reports : PR, vol. 70, no. 5, 2018, pp. 1015-1022.
Ostadhadi S, Shakiba S, Norouzi-Javidan A, et al. The role of nitric oxide-cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test. Pharmacol Rep. 2018;70(5):1015-1022.
Ostadhadi, S., Shakiba, S., Norouzi-Javidan, A., Nikoui, V., Zolfaghari, S., Chamanara, M., & Dehpour, A. R. (2018). The role of nitric oxide-cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test. Pharmacological Reports : PR, 70(5), pp. 1015-1022. doi:10.1016/j.pharep.2018.05.004.
Ostadhadi S, et al. The Role of Nitric oxide-cGMP Pathway in Selegiline Antidepressant-like Effect in the Mice Forced Swim Test. Pharmacol Rep. 2018;70(5):1015-1022. PubMed PMID: 30144662.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of nitric oxide-cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test. AU - Ostadhadi,Sattar, AU - Shakiba,Saeed, AU - Norouzi-Javidan,Abbas, AU - Nikoui,Vahid, AU - Zolfaghari,Samira, AU - Chamanara,Mohsen, AU - Dehpour,Ahmad-Reza, Y1 - 2018/05/13/ PY - 2017/04/09/received PY - 2018/04/03/revised PY - 2018/05/11/accepted PY - 2018/8/26/pubmed PY - 2018/11/18/medline PY - 2018/8/26/entrez KW - Depression KW - Forced swimming test KW - Mice KW - Nitric oxide KW - Selegiline SP - 1015 EP - 1022 JF - Pharmacological reports : PR JO - Pharmacol Rep VL - 70 IS - 5 N2 - BACKGROUND: Considering the pivotal role of nitric oxide (NO) pathway in depressive disorders, the aim of the present study was to investigate the antidepressant-like effect of selegiline in mice forced swimming test (FST), and possible involvement of NO-cyclic guanosine monophosphate (cGMP) pathway in this action. METHODS: After assessment of locomotor activity in open-field test, mice were forced to swim individually and the immobility time of the last 4min was evaluated. All drugs were given intraperitoneally (ip). RESULTS: Selegiline (10mg/kg) decreased the immobility time in the FST similar to fluoxetine (20mg/kg). Pretreatment with l-arginine (NO precursor, 750mg/kg) or sildenafil (a phosphodiesterase 5 inhibitor, 5mg/kg) significantly reversed the selegiline anti-immobility effect. Sub-effective dose of selegiline (1mg/kg) showed a synergistic antidepressant effect with NG-nitro-l-arginine methyl ester (L-NAME, inhibitor of NO synthase, 10mg/kg) or 7-nitroindazole (specific neuronal NO synthase inhibitor, 30mg/kg), but not with aminoguanidine (specific inducible NO synthase inhibitor, 50mg/kg). Pretreatment of mice with methylene blue (an inhibitor of NO synthase and soluble guanylyl cyclase, 10mg/kg) significantly produced a synergistic response with the sub-effective dose of selegiline. Neither of the drugs changed the locomotor activity. Also, hippocampal and prefrontal cortex (PFC) nitrite content was significantly lower in selegiline-injected mice compared to saline-administrated mice. Also, co-injection of 7-nitroindazole with selegiline produced a significant reduction in hippocampal or PFC nitrite contents. CONCLUSIONS: It is concluded that selegiline possesses antidepressant-like effect in mice FST through inhibition of l-arginine-NO-cyclic guanosine monophosphate pathway. SN - 1734-1140 UR - https://www.unboundmedicine.com/medline/citation/30144662/The_role_of_nitric_oxide_cGMP_pathway_in_selegiline_antidepressant_like_effect_in_the_mice_forced_swim_test_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1734-1140(17)30260-8 DB - PRIME DP - Unbound Medicine ER -