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 I1/alpha2-adrenoceptor antagonist), idazoxan (0.06 mg/kg, i.p., an imidazoline I2/alpha2-adrenoceptor antagonist) and antazoline (5 mg/kg, i.p., a ligand with high affinity for the I2 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 I1/alpha2-adrenoceptor agonist), moxonidine (0.5 mg/kg, i.p., an imidazoline I1/alpha2-adrenoceptor agonist), antazoline (1 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 alpha2-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 antazoline (5 mg/kg, i.p.), but not with efaroxan (1 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 I1 and I2 receptors.
Zeidan
Mariana P
MP
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, 88040-900, SC, Brazil.
Zomkowski
Andréa D E
AD
Rosa
Angelo O
AO
Rodrigues
Ana Lúcia S
AL
Gabilan
Nelson H
NH
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000865:Antazoline / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology*; D001572:Benzofurans / Q000494:pharmacology; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D007093:Imidazoles / Q000494:pharmacology; D054755:Imidazoline Receptors; D008297:Male; D051379:Mice; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D011955:Receptors, Drug / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013550:Swimming
D000928:Antidepressive Agents; D001572:Benzofurans; D007093:Imidazoles; D054755:Imidazoline Receptors; D018341:Receptors, Adrenergic, alpha-2; D011955:Receptors, Drug; D016194:Receptors, N-Methyl-D-Aspartate; D000376:Agmatine; C043482:moxonidine; D000865:Antazoline; C062597:efaroxan; D003000:Clonidine