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 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.
Kessler RC, Merikangas KR, Wang PS. Prevalence, comorbidity, and service utilization for mood disorders in the United States at the beginning of the twenty-first century. Annu Rev Clin Psychol 2007;3:137-58.
Berton O, Nestler EJ. New approaches to antidepressant drug discovery: beyond monoamines. Nat Rev Neurosci 2006;7:137-51.
Cakmakci E, Caliskan KC, Tabakci ON, Tahtabasi M, Karpat Z. Percutaneous liver biopsies guided with
ultrasonography: a case series. Iran J Radiol 2013;10:182-4.
Arroll B, Macgillivray S, Ogston S, Reid I, Sullivan F, Williams B, et al. Efficacy and tolerability of tricyclic antidepressants and SSRIs compared with placebo for treatment of depression in primary care: a meta-analysis. Ann Fam Med 2005;3:449-56.
Lidbrink P, Jonsson G, Fuxe K. The effect of imipramine-like drugs and antihistamine drugs on uptake mechanisms in the central noradrenaline and 5-hydroxytryptamine neurons. Neuropharmacology 1971;10:521-30.
Shishido S, Oishi R, Saeki K. In vivo effects of some histamine H1-receptor antagonists on monoamine metabolism in the mouse brain. Naunyn Schmiedebergs Arch Pharmacol 1991;343:185-9.
Tatsumi M, Groshan K, Blakely RD, Richelson E. Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol 1997;340:249-58.
Onodera K, Yamatodani A, Watanabe T, Wada H. Neuropharmacology of the histaminergic neuron system in the brain and its relationship with behavioral disorders. Progr Neurobiol 1994;42:685-702.
Goodwin RD. Panic disorder treated with the antihistamine chlorpheniramine. Ann Allergy Asthma Immunol 2003;90:361-2.
Gammoh O, Mayyas F, Darwish Elhajji F. Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety. Biomed Rep 2017;6:675-80.
Aslanian R, Mutahi Mw, Shih NY, Piwinski JJ, West R, Williams SM, et al. Identification of a dual histamine H1/H3 receptor ligand based on the H1 antagonist chlorpheniramine. Bioorg Med Chem Lett 2003;13:1959-61.
Hirano S, Miyata S, Onodera K, Kamei J. Effects of histamine H 1 receptor antagonists on depressive-like behavior in diabetic mice. Pharmacol Biochem Behav 2006;83:214-20.
Rogoz Z, Skuza G, Sowinska H. Effects of antihistaminic drugs in tests for antidepressant action. Pol J Pharmacol Pharm 1981;33:321-35.
Hirano S, Miyata S, Onodera K, Kamei J. Involvement of dopamine D1 receptors and alpha1-adrenoceptors in the antidepressant-like effect of chlorpheniramine in the mouse tail suspension test. Eur J Pharmacol 2007;562:72-6.
Kurauchi Y, Hisatsune A, Isohama Y, Sawa T, Akaike T, Shudo K, et al. Midbrain dopaminergic neurons utilize nitric oxide/cyclic GMP signaling to recruit ERK that links retinoic acid receptor stimulation to up‐regulation ofBDNF. J Neurochem 2011;116:323-33.
Klejbor I, Domaradzka-Pytel B, Ludkiewicz B, Wójcik S, Moryś J. The relationships between neurons containing dopamine and nitric oxide synthase in the ventral tegmental area. Folia Histochem Cytobiol 2004;42:83-7.
Surmeier DJ1, Bargas J, Hemmings HC Jr, Nairn AC, Greengard P. Modulation of calcium currents by a D 1 dopaminergic protein kinase/phosphatase cascade in rat neostriatal neurons. Neuron 1995;14:385-97.
Förstermann U, Sessa WC. Nitric oxide synthases: regulation and function. Eur Heart J 2012;33:829-37.
Garthwaite J, Boulton CL. Nitric oxide signaling in the central nervous system. Annu Rev Physiol 1995;57:683-706.
Salter M, Knowles RG, Moncada S. Widespread tissue distribution, species distribution and changes in activity of Ca(2+)-dependent and Ca(2+)-independent nitric oxide synthases. FEBS Lett 1991;291:145-9.
Joca SR, Guimaraes FS. Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressant-like effects. Psychopharmacology (Berl) 2006;185:298-305.
Denninger JW, Marletta MA. Guanylate cyclase and the NO/cGMP signaling pathway. Biochim Biophys Acta 1999;1411:334-50.
Harkin AJ, Bruce KH, Craft B, Paul IA. Nitric oxide synthase inhibitors have antidepressant-like properties in mice 1. Acute treatments are active in the forced swim test. Eur J Pharmacol;1999;372:207-13.
Rosa AO, Lin J, Calixto JB, Santos AR, Rodrigues AL. Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice. Behav Brain Res 2003;144:87-93.
Ostadhadi S, Ahangari M, Nikoui V, Norouzi-Javidan A, Zolfaghari S, Jazaeri F, et al. Pharmacological evidence for the involvement of the NMDA receptor and nitric oxide pathway in the antidepressant-like effect of lamotrigine in the mouse forced swimming test. Biomed Pharmacother 2016;82:713-21.
Haj-Mirzaian A, Kordjazy N, Amiri S, Haj-Mirzaian A, Amini-Khoei H, Ostadhadi S, et al. Involvement of nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of tropisetron and ondansetron in mice forced swimming test and tail suspension test. Eur J Pharmacol 2016;780:71-81.
Khan MI, Ostadhadi S, Zolfaghari S, Ejtemaei Mehr S, Hassanzadeh G, Dehpour AR, The involvement of NMDA receptor/NO/cGMP pathway in the antidepressant like effects of baclofen in mouse force swimming test. Neurosci Lett 2016;612:52-61.
Ostadhadi S, Kordjazy N, Haj-Mirzaian A, Ameli S,
Akhlaghipour G, Dehpour A. Involvement of NO/cGMP pathway in the antidepressant-like effect of gabapentin in mouse forced swimming test. Naunyn Schmiedebergs Arch Pharmacol 2016;389:393-402.
Ostadhadi S, Khan MI, Norouzi-Javidan A, Chamanara M, Jazaeri F, Zolfaghari S, et al. Involvement of NMDA receptors and l-arginine/nitric oxide/cyclic guanosine monophosphate pathway in the antidepressant-like effects of topiramate in mice forced swimming test. Brain Res Bull 2016;122:62-70.
National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals. Guide for the Care and Use of Laboratory Animals. 8th ed. Washington DC: National Academies Press (US), 2011.
Turner PV, Brabb T, Pekow C, Vasbinder MA. Administration of substances to laboratory animals: routes of administration and factors to consider. J Am Assoc Lab Anim Sci 2011;50:600-13.
Ostadhadi S, Haj-Mirzaian A, Nikoui V, Kordjazy N, Dehpour AR. Involvement of opioid system in antidepressant-like effect of the cannabinoid CB1 receptor inverse agonist AM-251 after physical stress in mice. Clin Exp Pharmacol Physiol 2016;43:203-12.
Khaloo P, Sadeghi B, Ostadhadi S, Norouzi-Javidan A, Haj-Mirzaian A, Zolfagharie S, et al. Lithium attenuated the behavioral despair induced by acute neurogenic stress through blockade of opioid receptors in mice. Biomed Pharmacother 2016;83:1006-15.
Haj-Mirzaian A, Kordjazy N, Haj-Mirzaian A, Ostadhadi S, Ghasemi M, Amiri S. et al. Evidence for the involvement of NMDA receptors in the antidepressant-like effect of nicotine in mouse forced swimming and tail suspension tests. Psychopharmacology (Berl) 2015;232:3551-61.
Porsolt RD, Bertin A, Jalfre M. Behavioral despair in mice: a primary screening test for antidepressants. Arch Int Pharmacodyn Ther 1977;229:327-36.
Kordjazy N, Haj-Mirzaian A, Amiri S, Ostadhadi S, Amini-Khoei H, Dehpour AR. Involvement of N-methyl-d-aspartate receptors in the antidepressant-like effect of 5-hydroxytryptamine 3 antagonists in mouse forced swimming test and tail suspension test. Pharmacolo Biochem Behav 2016;141:1-9.
Kaster MP, Rosa AO, Santos AR, Rodrigues AL. Involvement of nitric oxide-cGMP pathway in the antidepressant-like effects of adenosine in the forced swimming test. Int J Neuropsychopharmacol 2005;8:601-6.
Noguchi S, Fukuda Y, Inukai T. Possible contributory role of the central histaminergic system in the forced swimming model. Arzneimittelforschung 1992;42:611-3
Lamberti C, Ipponi A, Bartolini A, Schunack W, Malmberg-Aiello P. Antidepressant‐like effects of endogenous histamine and of two histamine H1 receptor agonists in the mouse forced swim test. Br J Pharmacol 1998;123:1331-6.
Yanai K, Son LZ, Endou M, Sakurai E, Nakagawasai O, Tadano T, et al. Behavioural characterization and amounts of brain monoamines and their metabolites in mice lacking histamine H1 receptors. Neuroscience 1998;87:479-87.
Hirano S, Miyata S, Onodera K, Kamei J. Effects of histamine H1 receptor antagonists on depressive-like behavior in diabetic mice. Pharmacol Biochem Behav 2006;83:214-20.
Suzuki T, Mori T, Tsuji M, Nomura M, Misawa M, Onodera K. Evaluation of the histamine H1-antagonist-induced place preference in rats. Jpn J Pharmacol 2001;81:332-8.
Kordjazy N, Haj-Mirzaian A, Amiri S, Ostadhadi S, Kordjazy M, Sharifzadeh M, et al. Elevated level of nitric oxide mediates the anti-depressant effect of rubidium chloride in mice. Eur J Pharmacol 2015;762:411-8.
Karatinos J, Rosse RB, Deutsch SI. The nitric oxide pathway: potential implications for treatment of neuropsychiatric disorders. Clin Neuropharmacol 1995;18:482-99.
Heiberg IL, Wegener G, Rosenberg R. Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats. Behav Brain Res 2002;134:479-84.
Selek S, Savas HA, Gergerlioglu HS, Bulbul F, Uz E, Yumru M. The course of nitric oxide and superoxide dismutase during treatment of bipolar depressive episode. J Affect Disord 2008;107:89-94.
Ghasemi M, Sadeghipour H, Mosleh A, Sadeghipour HR, Mani AR, Dehpour AR. Nitric oxide involvement in the antidepressant-like effects of acute lithium administration in the mouse forced swimming test. Eur Neuropsychopharmacol 2008;18:323-32.
Herken H, Gurel A, Selek S, Armutcu F, Ozen ME, Bulut M, et al. Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment. Arch Med Res 2007;38:247-52.
Chrapko WE, Jurasz P, Radomski MW, Lara N, Archer SL, Le Mellédo JM. Decreased platelet nitric oxide synthase activity and plasma nitric oxide metabolites in major depressive disorder. Biol Psychiatry 2004;56:129-34.
da Silva GD, Matteussi AS, dos Santos AR, Calixto JB, Rodrigues AL. Evidence for dual effects of nitric oxide in the forced swimming test and in the tail suspension test in
mice. Neuroreport 2000;11:3699-702.
Foroutan A, Haddadi NS, Ostadhadi S, Sistany N, Dehpour AR. Chloroquine-induced scratching is mediated by NO/cGMP pathway in mice. Pharmacol Biochem Behav 2015;134:79-84.
Kawabata A, Manabe S, Manabe Y, Takagi H. Effect of topical administration of l‐arginine on formalin‐induced nociception in the mouse: a dual role of peripherally formed NO in pain modulation. Br J Pharmacol 1994;112:547-50.
Liaudet L, Soriano FG, Szabó C. Biology of nitric oxide signaling. Crit Care Med 2000;28:N37-52.
Clancy RM, Amin AR, Abramson SB. The role of nitric oxide in inflammation and immunity. Arthritis Rheum 1998;41:1141-51.
Iadecola C. Bright and dark sides of nitric oxide in ischemic brain injury. Trends Neurosci 1997;20:132-9.
Colasanti M. Suzuki H. The dual personality of NO. Trends Pharmacol Sci 2000;21:249-52.
Inan SY, Yalcin I, Aksu F. Dual effects of nitric oxide in the mouse forced swimming test: possible contribution of nitric oxide-mediated serotonin release and potassium channel modulation. Pharmacol Biochem Behav 2004;77:457-64.
Gammoh O, Mayyas F, Darwish Elhajji F. Chlorpheniramine and escitalopram: Similar antidepressant and nitric oxide lowering roles in a mouse model of anxiety. Biomed Rep 2017;6:675-680.
Wegener G, Volke V, Rosenberg R. Endogenous nitric oxide decreases hippocampal levels of serotonin and dopamine in vivo. Br J Pharmacol 2000;130:575-80.
Harkin A, Connor TJ, Burns MP, Kelly JP. Nitric oxide synthase inhibitors augment the effects of serotonin re-uptake inhibitors in the forced swimming test. Eur Neuropsychopharmacol 2004;14:274-81.
Kulkarni SK, Dhir A. Possible involvement of L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling pathway in the antidepressant activity of berberine chloride. Eur J Pharmacol 2007;569:77-83.
Zomkowski AD, Engel D, Gabilan NH, Rodrigues AL. Involvement of NMDA receptors and L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effects of escitalopram in the forced swimming test. Eur Neuropsychopharmacol 2010;20:793-801.
Steinert JR, Chernova T, Forsythe ID. Nitric oxide signaling in brain function, dysfunction, and dementia. Neuroscientist 2010;16:435-52.
Harvey BH, Oosthuizen F, Brand L, Wegener G, Stein DJ. Stress–restress evokes sustained iNOS activity and altered GABA levels and NMDA receptors in rat hippocampus Psychopharmacology 2004;175:494-502.
Francis H, Glaser S, Demorrow S, Gaudio E, Ueno Y, Venter J, et al. Small mouse cholangiocytes proliferate in response to H1 histamine receptor stimulation by activation of the IP3/CaMK I/CREB pathway. Am J Physiol Cell Physiol 2008;295:C499-513.
Eckeli AL, Dach F, Rodrigues ALS. Acute treatments with GMP produce antidepressant‐like effects in mice. Neuroreport 2000;11:1839-43.
Garthwaite J, Boulton C. Nitric oxide signaling in the central nervous system. Ann Rev Physiol 1995;57:683-706.
Hartell NA. Inhibition of cGMP breakdown promotes the induction of cerebellar long-term depression. J Neurosci 1996;16:2881-90.
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|Chlorpheniramine Nitric oxide Cyclic guanosine monophosphate Forced swim test Mice|
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