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The role of nitric oxide—cGMP pathway in selegiline antidepressant-like effect in the mice forced swim test

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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 4 min was evaluated. All drugs were given intraperitoneally (ip).

Results

Selegiline (10 mg/kg) decreased the immobility time in the FST similar to fluoxetine (20 mg/kg). Pretreatment with l-arginine (NO precursor, 750 mg/kg) or sildenafil (a phosphodiesterase 5 inhibitor, 5 mg/kg) significantly reversed the selegiline anti-immobility effect. Sub-effective dose of selegiline (1 mg/kg) showed a synergistic antidepressant effect with NG-nitro-l-arginine methyl ester (L-NAME, inhibitor of NO synthase, 10 mg/kg) or 7-nitroindazole (specific neuronal NO synthase inhibitor, 30 mg/kg), but not with aminoguanidine (specific inducible NO synthase inhibitor, 50 mg/kg). Pretreatment of mice with methylene blue (an inhibitor of NO synthase and soluble guanylyl cyclase, 10 mg/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.

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Authors and Affiliations

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

    Sattar Ostadhadi, Saeed Shakiba, Abbas Norouzi-Javidan & Ahmad-Reza Dehpour

  2. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Sattar Ostadhadi, Saeed Shakiba, Mohsen Chamanara & Ahmad-Reza Dehpour

  3. Razi Drug Research Center, Iran University of Medical Sciences, Tehran, Iran

    Vahid Nikoui

  4. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

    Sattar Ostadhadi, Saeed Shakiba & Ahmad-Reza Dehpour

  5. Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran

    Samira Zolfaghari

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  1. Sattar Ostadhadi
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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 70, 1015–1022 (2018). https://doi.org/10.1016/j.pharep.2018.05.004

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