title: Evidences for the agmatine involvement in antidepressant like effect of bupropion in mouse forced swim test.
abstract: 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 (40 μg/mouse, icv), an agmatine biosynthetic precursor, ornithine decarboxylase inhibitor, dl-α-difluoromethyl ornithine hydrochloride, DFMO (12.5 μg/mouse, icv), diamine oxidase inhibitor, aminoguanidine (6.5 μg/mouse, icv) and agmatinase inhibitor, arcaine (50 μg/mouse, icv) as well as imidazoline I1 receptor agonists, moxonidine (0.25mg/kg, ip) and clonidine (0.015 mg/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.
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur, Maharashtra 441 002, India.
authors.forename: Nandkishor R
authors.initials: NR
authors.lastname: Kotagale
authors.forename: Sunil J
authors.initials: SJ
authors.lastname: Tripathi
authors.forename: Manish M
authors.initials: MM
authors.lastname: Aglawe
authors.forename: Chandrabhan T
authors.initials: CT
authors.lastname: Chopde
authors.forename: Milind J
authors.initials: MJ
authors.lastname: Umekar
authors.forename: Brijesh G
authors.initials: BG
authors.lastname: Taksande
mesh_terms: D000376:Agmatine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D001572:Benzofurans / Q000494:pharmacology; D001645:Biguanides / Q000008:administration & dosage / Q000494:pharmacology; D016642:Bupropion / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D000518:Eflornithine / Q000008:administration & dosage / Q000494:pharmacology; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology; D019329:Idazoxan / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D046353:Immobility Response, Tonic / Q000187:drug effects* / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D001572:Benzofurans; D001645:Biguanides; D006146:Guanidines; D007093:Imidazoles; D016642:Bupropion; C006624:arcaine; D000376:Agmatine; C103723:2-(2-benzofuranyl)-2-imidazoline; D001120:Arginine; C043482:moxonidine; C062597:efaroxan; D003000:Clonidine; C004479:pimagedine; D019329:Idazoxan; D000518:Eflornithine