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Imidazoline binding sites mediates anticompulsive-like effect of agmatine in marble-burying behavior in mice.

Authors
  • Dixit, Madhura P1
  • Thakre, Prajwal P1
  • Pannase, Akshay S1
  • Aglawe, Manish M1
  • Taksande, Brijesh G1
  • Kotagale, Nandkishor R2
  • 1 Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India. , (India)
  • 2 Division of Neuroscience, Department of Pharmacology, Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India. Electronic address: [email protected] , (India)
Type
Published Article
Journal
European journal of pharmacology
Publication Date
Jun 05, 2014
Volume
732
Pages
26–31
Identifiers
DOI: 10.1016/j.ejphar.2014.02.045
PMID: 24657463
Source
Medline
Keywords
License
Unknown

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.

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