Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test

• Published in: Pharmacology, biochemistry and behavior Vol. 107; pp. 42 - 47
• Main Authors: Kotagale, Nandkishor R., Tripathi, Sunil J., Aglawe, Manish M., Chopde, Chandrabhan T., Umekar, Milind J., Taksande, Brijesh G.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2013
• Subjects: Agmatine; Agmatine - administration & dosage; Agmatine - antagonists & inhibitors; Agmatine - pharmacology; Animals; Antidepressive Agents - administration & dosage; Antidepressive Agents - pharmacology; Arginine - administration & dosage; Arginine - pharmacology; Benzofurans - pharmacology; Biguanides - administration & dosage; Biguanides - pharmacology; Bupropion; Bupropion - administration & dosage; Bupropion - antagonists & inhibitors; Bupropion - pharmacology; Clonidine - pharmacology; Depression; Dose-Response Relationship, Drug; Drug Interactions; Eflornithine - administration & dosage; Eflornithine - pharmacology; FST; Guanidines - administration & dosage; Guanidines - pharmacology; Idazoxan - pharmacology; Imidazoles - pharmacology; Imidazoline receptors; Immobility Response, Tonic - drug effects; Immobility Response, Tonic - physiology; Injections, Intraventricular; Male; Mice; Motor Activity - drug effects; Depression; Imidazoline receptors; Bupropion; Agmatine; FST
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2013.03.019

Although bupropion has been widely used in the treatment of depression, the precise mechanism of its therapeutic actions is not fully understood. The present study investigated the role of agmatine in an antidepressant like effect of bupropion in mouse forced swim test. The antidepressant like effect of bupropion was potentiated by pretreatment with agmatine (10–20mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40μg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5μg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5μg/mouse, icv) and agmatinase inhibitor, arcaine (50μg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015mg/kg, ip) and imidazoline I2 receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5mg/kg, ip). Conversely, prior administration of I1 receptor antagonist, efaroxan (1mg/kg, ip) and I2 receptor antagonist, idazoxan (0.25mg/kg, ip) blocked the antidepressant like effect of bupropion and its synergistic combination with agmatine. These results demonstrate involvement of agmatine in the antidepressant like effect of bupropion and suggest agmatine and imidazoline receptors as a potential therapeutic target for the treatment of depressive disorders. •Agmatine and its modulators potentiated the anti-immobility effect of bupropion.•Imidazoline receptor agonists potentiated the effect of bupropion in FST.•Imidazoline receptor antagonists blocked the anti-immobility effect of bupropion.•Imidazoline receptor ligands may be a developed for antidepressant therapy.