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



Shakiba S1, 2, 3 ; Rajai N2, 3 ; Qaempanah M2 ; Haddadi NS2, 3 ; Norouzijavidan A1 ; Akbarian R2 ; Ostadhadi S1, 2 ; Dehpour AR1, 2, 3
Authors
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Authors Affiliations
  1. 1. Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Departments of Pharmacology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. Experimental Medicine Research Center, Tehran University of Medical Sciences, Tehran, Iran

Source: Acta Medica Iranica Published:2018

Abstract

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. © 2018 Tehran University of Medical Sciences. All rights reserved.
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