title: Imidazoline binding sites mediates anticompulsive-like effect of agmatine in marble-burying behavior in mice.
abstract: Agmatine is a cationic amine formed by decarboxylation of l-arginine by the mitochondrial enzyme arginine decarboxylase and widely distributed in mammalian brain. Although the precise function of endogenous agmatine has been largely remained unclear, its exogenous administration demonstrated beneficial effects in several neurological and psychiatric disorders. This study was planned to examine the role of imidazoline binding sites in the anticompulsive-like effect of agmatine on marble-burying behavior. Agmatine (20 and 40mg/kg, ip), mixed imidazoline I1/α2 agonists clonidine (60µg/kg, ip) and moxonidine (0.25mg/kg, ip), and imidazoline I2 agonist 2- BFI (10mg/kg, ip) showed significant inhibition of marble burying behavior in mice. In combination studies, the anticompulsive-like effect of agmatine (10mg/kg, ip) was significantly potentiated by prior administration of moxonidine (0.25mg/kg, ip) or clonidine (30µg/kg,) or 2-BFI (5mg/kg, ip). Conversely, efaroxan (1mg/kg, ip), an I1 antagonist and idazoxan (0.25mg/kg, ip), an I2 antagonist completely blocked the anticompulsive-like effect of agmatine (10mg/kg, ip). These drugs at doses used here did not influence the basal locomotor activity in experimental animals. These results clearly indicated the involvement of imidazoline binding sites in anti-compulsive-like effect of agmatine. Thus, imidazoline binding sites can be explored further as novel therapeutic target for treatment of anxiety and obsessive compulsive disorders.
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India.
authors.forename: Madhura P
authors.initials: MP
authors.lastname: Dixit
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India.
authors.forename: Prajwal P
authors.initials: PP
authors.lastname: Thakre
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India.
authors.forename: Akshay S
authors.initials: AS
authors.lastname: Pannase
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India.
authors.forename: Manish M
authors.initials: MM
authors.lastname: Aglawe
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India.
authors.forename: Brijesh G
authors.initials: BG
authors.lastname: Taksande
authors.affiliation: Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India. Electronic address: nandukotagale@gmail.com.
authors.forename: Nandkishor R
authors.initials: NR
authors.lastname: Kotagale
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000376:Agmatine / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D003192:Compulsive Behavior / Q000188:drug therapy* / Q000523:psychology*; D004305:Dose-Response Relationship, Drug; D054755:Imidazoline Receptors / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D048288:Imidazolines / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects
chemical_list: D000316:Adrenergic alpha-Agonists; D054755:Imidazoline Receptors; D048288:Imidazolines; D000376:Agmatine
keywords: Agmatine; Imidazoline binding sites; Marble burying behavior; Obsessive compulsive disorder