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

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• 作者：Nandkishor R. Kotagale ; Sunil J. Tripathi ; Manish M. Aglawe ; Chandrabhan T. Chopde ; Milind J. Umekar ; Brijesh G. Taksande ; ^{b_taksande@rediffmail.com}
• 关键词：Bupropion ; Agmatine ; Imidazoline receptors ; Depression ; FST
• 刊名：Pharmacology Biochemistry and Behavior
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：107
• 期：Complete
• 页码：42-47
• 全文大小：697 K

文摘

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 (10-20 mg/kg, ip) and by the drugs known to increase endogenous agmatine levels in brain viz., l-arginine (40 ¦Ìg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-¦Á-difluoromethyl ornithine hydrochloride, DFMO (12.5 ¦Ìg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 ¦Ìg/mouse, icv) and agmatinase inhibitor, arcaine (50 ¦Ìg/mouse, icv) as well as imidazoline I₁ receptor agonists, moxonidine (0.25 mg/kg, ip) and clonidine (0.015 mg/kg, ip) and imidazoline I₂ receptor agonist, 2-(2-benzofuranyl)-2-imidazoline hydrochloride, 2-BFI (5 mg/kg, ip). Conversely, prior administration of I₁ receptor antagonist, efaroxan (1 mg/kg, ip) and I₂ receptor antagonist, idazoxan (0.25 mg/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.