Agmatine, an endogenous imidazoline receptor ligand modulates ethanol anxiolysis and withdrawal anxiety in rats.
Present study investigated the role of agmatine in ethanol-induced anxiolysis and withdrawal anxiety using elevated plus maze (EPM) test in rats. The anxiolytic-like effect of ethanol was potentiated by pretreatment with imidazoline I(1)/I(2) receptor agonist agmatine (10-20 mg/kg, i.p.), imidazoline I(1) receptor agonists, moxonidine (0.25 mg/kg, i.p.) and clonidine (0.015 mg/kg, i.p.), imidazoline I(2) receptor agonist, 2-BFI (5 mg/kg, i.p.) as well as by the drugs known to increase endogenous agmatine levels in brain viz., L-arginine, an agmatine biosynthetic precursor (100 microg/rat, i.c.v.), ornithine decarboxylase inhibitor, DFMO (125 microg/rat, i.c.v.), diamine oxidase inhibitor, aminoguanidine (65 microg/rat, i.c.v.) and agmatinase inhibitor, arcaine (50 microg/rat, i.c.v.). Conversely, prior administration of I(1) receptor antagonist, efaroxan (1 mg/kg, i.p.), I(2) receptor antagonist, idazoxan (0.25mg/kg, i.p.) and arginine decarboxylase inhibitor, D-arginine (100 microg/rat, i.c.v.) blocked the anxiolytic-like effect of ethanol. Moreover, ethanol withdrawal anxiety was markedly attenuated by agmatine (10-20 mg/kg, i.p.), moxonidine (0.25 mg/kg, i.p.), clonidine (0.015 mg/kg, i.p.), 2-BFI (5 mg/kg, i.p.), L-arginine (100 microg/rat, i.c.v.), DFMO (125 microg/rat, i.c.v.), aminoguanidine (65 microg/rat, i.c.v.) and arcaine (50 microg/rat, i.c.v.). The anti-anxiety effect of agmatine in ethanol-withdrawn rats was completely blocked by efaroxan (1 mg/kg, i.p.) and idazoxan (0.25 mg/kg, i.p.). These results suggest that agmatine and imidazoline receptor system may be implicated in ethanol-induced anxiolysis and withdrawal anxiety and strongly support further investigation of agmatine in ethanol dependence mechanism. The data also project agmatine as a potential therapeutic target in overcoming alcohol withdrawal symptoms such as anxiety.
Taksande
Brijesh G
BG
Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar, College of Pharmacy, New Kamptee, Nagpur, MS, India.
Kotagale
Nandkishor R
NR
Patel
Mital R
MR
Shelkar
Gajanan P
GP
Ugale
Rajesh R
RR
Chopde
Chandrabhan T
CT
D000376:Agmatine / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology; D001120:Arginine / Q000494:pharmacology; D001645:Biguanides / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000518:Eflornithine / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D006146:Guanidines / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors / Q000737:chemistry / Q000378:metabolism*; D008024:Ligands; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000188:drug therapy*
D014151:Anti-Anxiety Agents; D001645:Biguanides; D006146:Guanidines; D007093:Imidazoles; D054755:Imidazoline Receptors; D008024:Ligands; D000431:Ethanol; C006624:arcaine; D000376:Agmatine; D001120:Arginine; C043482:moxonidine; D003000:Clonidine; C004479:pimagedine; D000518:Eflornithine