Evidence for imidazoline receptors involvement in the agmatine antidepressant-like effect in the forced swimming test

This study investigated the involvement of the imidazoline receptors in the antidepressant-like effect of agmatine in the forced swimming test. The antidepressant-like effects of agmatine (10 mg/kg, i.p.) in the forced swimming test was blocked by pretreatment of mice with efaroxan (1 mg/kg, i.p., an imidazoline I-1/alpha(2)-adrenoceptor antagonist), idazoxan (0.06 mg/kg, i.p., an imidazoline I-2/alpha(2)-adrenoceptor antagonist) and amazoline (5 mg/kg, i.p., a ligand with high affinity for the 12 receptor). A subeffective dose of agmatine (0.001 mg/kg, i.p.) produced a synergistic antidepressant-like effect with clonidine (0.06 mg/kg, i.p, an imidazoline I-1/alpha(2)-adrenoceptor agonist), moxonidine (0.5 mg/kg, i.p., an imidazoline I-1/alpha(2)-adrenoceptor agonist), amazoline (I mg/kg, i.p.) and MK-801 (0.001 mg/kg, i.p., a non-competitive NMDA receptor antagonist), but not with efaroxan (1 mg/kg, i.p.) and idazoxan (0.06 mg/kg, i.p.). Pretreatment of mice with yohimbine (1 mg/kg, i.p., an alpha(2)-adrenoceptor antagonist) blocked the synergistic antidepressant-like effect of agmatine (0.001 mg/kg, i.p.) with clonidine (0.06 mg/kg, i.p). A subeffective dose of MK-801 (0.001 mg/kg, i.p.) produced a synergistic antidepressant-like effect with amazoline (5 mg/kg, i.p.), but not with efaroxan (I mg/kg, i.p.) or idazoxan (0.06 mg/kg, i.p.). In conclusion, this study suggests that the anti-immobility effect of agmatine in the forced swimming test is dependent on its interaction with imidazoline I-1 and I-2 receptors. (c) 2007 Elsevier B.V. All rights reserved.