Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test

Chlorpheniramine, a first-generation antihistamine, is widely used for allergic reactions. Previous studies showed the interaction between antidepressant activity and nitric oxide and cyclic guanosine monophosphate (NO/cGMP) pathway. Thus, we aimed to assess the possible involvement of NO/cGMP pathw...

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Main Authors: Saeed Shakiba, Nazanin Rajai, Mehdi Qaempanah, Nazgol‐Sadat Haddadi, Abbas Norouzi-Javidan, Reyhaneh Akbarian, Sattar Ostadhadi, Ahmad-Reza Dehpour
Format: Article
Language:English
Published: Tehran University of Medical Sciences 2018-11-01
Series:Acta Medica Iranica
Subjects:
Online Access:https://acta.tums.ac.ir/index.php/acta/article/view/6933
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author Saeed Shakiba
Nazanin Rajai
Mehdi Qaempanah
Nazgol‐Sadat Haddadi
Abbas Norouzi-Javidan
Reyhaneh Akbarian
Sattar Ostadhadi
Ahmad-Reza Dehpour
author_facet Saeed Shakiba
Nazanin Rajai
Mehdi Qaempanah
Nazgol‐Sadat Haddadi
Abbas Norouzi-Javidan
Reyhaneh Akbarian
Sattar Ostadhadi
Ahmad-Reza Dehpour
author_sort Saeed Shakiba
collection DOAJ
description Chlorpheniramine, a first-generation antihistamine, is widely used for allergic reactions. Previous studies showed the interaction between antidepressant activity and nitric oxide and cyclic guanosine monophosphate (NO/cGMP) pathway. Thus, we aimed to assess the possible involvement of NO/cGMP pathway in this effect using forced swim test (FST) in male mice. To evaluate the locomotor activity and immobility time, we performed open field test (OFT) and FST on each mouse. Chlorpheniramine was administered intraperitoneally (i.p.) (0.1, 0.3, 1, 10 mg/kg) 30 minutes before FST. To assess the involvement of NO/cGMP pathway, a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10mg/kg, i.p.), a selective inducible NOS (iNOS) inhibitor, aminoguanidine (50 mg/kg, i.p.), a selective neural NOS (nNOS) inhibitor, 7-nitroindazole (7-NI, 30 mg/kg, i.p.), a NO precursor, L-arginine (750 mg/kg, i.p.) and a selective phosphodiesterase-5 (PDE-5) inhibitor, sildenafil (5 mg/kg, i.p.) was co-administered with chlorpheniramine. Chlorpheniramine significantly decreased the immobility time at doses of 1mg/kg (P<0.01) and 10 mg/kg (P<0.001). Administration of L-NAME (P<0.01) and 7-NI enhanced the anti-immobility activity of chlorpheniramine (P<0.001), while aminoguanidine did not have any significant effects on the immobility time (P>0.05). Moreover, pretreatment with L-arginine (P<0.01) and sildenafil (P<0.001) significantly reduced the anti-immobility effect of chlorpheniramine. These treatments did not alter the locomotor activity of mice in OFT. Our results revealed that the antidepressant-like effect of chlorpheniramine is mediated through inhibition of NO/cGMP pathway.
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spelling doaj.art-0f2f714ca9ab423690b709c2fb75bc382022-12-22T00:38:19ZengTehran University of Medical SciencesActa Medica Iranica0044-60251735-96942018-11-015686933Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim TestSaeed Shakiba0Nazanin Rajai1Mehdi Qaempanah2Nazgol‐Sadat Haddadi3Abbas Norouzi-Javidan4Reyhaneh Akbarian5Sattar Ostadhadi6Ahmad-Reza Dehpour7Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. AND Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND 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. AND 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.Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran. AND 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. AND Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. AND Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran.Chlorpheniramine, a first-generation antihistamine, is widely used for allergic reactions. Previous studies showed the interaction between antidepressant activity and nitric oxide and cyclic guanosine monophosphate (NO/cGMP) pathway. Thus, we aimed to assess the possible involvement of NO/cGMP pathway in this effect using forced swim test (FST) in male mice. To evaluate the locomotor activity and immobility time, we performed open field test (OFT) and FST on each mouse. Chlorpheniramine was administered intraperitoneally (i.p.) (0.1, 0.3, 1, 10 mg/kg) 30 minutes before FST. To assess the involvement of NO/cGMP pathway, a non-selective nitric oxide synthase (NOS) inhibitor, L-NAME (10mg/kg, i.p.), a selective inducible NOS (iNOS) inhibitor, aminoguanidine (50 mg/kg, i.p.), a selective neural NOS (nNOS) inhibitor, 7-nitroindazole (7-NI, 30 mg/kg, i.p.), a NO precursor, L-arginine (750 mg/kg, i.p.) and a selective phosphodiesterase-5 (PDE-5) inhibitor, sildenafil (5 mg/kg, i.p.) was co-administered with chlorpheniramine. Chlorpheniramine significantly decreased the immobility time at doses of 1mg/kg (P<0.01) and 10 mg/kg (P<0.001). Administration of L-NAME (P<0.01) and 7-NI enhanced the anti-immobility activity of chlorpheniramine (P<0.001), while aminoguanidine did not have any significant effects on the immobility time (P>0.05). Moreover, pretreatment with L-arginine (P<0.01) and sildenafil (P<0.001) significantly reduced the anti-immobility effect of chlorpheniramine. These treatments did not alter the locomotor activity of mice in OFT. Our results revealed that the antidepressant-like effect of chlorpheniramine is mediated through inhibition of NO/cGMP pathway.https://acta.tums.ac.ir/index.php/acta/article/view/6933ChlorpheniramineNitric oxideCyclic guanosine monophosphateForced swim testMice
spellingShingle Saeed Shakiba
Nazanin Rajai
Mehdi Qaempanah
Nazgol‐Sadat Haddadi
Abbas Norouzi-Javidan
Reyhaneh Akbarian
Sattar Ostadhadi
Ahmad-Reza Dehpour
Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test
Acta Medica Iranica
Chlorpheniramine
Nitric oxide
Cyclic guanosine monophosphate
Forced swim test
Mice
title Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test
title_full Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test
title_fullStr Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test
title_full_unstemmed Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test
title_short Pharmacological Profile for the Contribution of NO/cGMP Pathway on Chlorpheniramine Antidepressant-Like Effect in Mice Forced Swim Test
title_sort pharmacological profile for the contribution of no cgmp pathway on chlorpheniramine antidepressant like effect in mice forced swim test
topic Chlorpheniramine
Nitric oxide
Cyclic guanosine monophosphate
Forced swim test
Mice
url https://acta.tums.ac.ir/index.php/acta/article/view/6933
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