Zeidan Mariana P, Zomkowski Andréa D E, Rosa Angelo O, Rodrigues Ana Lúcia S, Gabilan Nelson H
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, 88040-900, SC, Brazil.
Eur J Pharmacol. 2007 Jun 22;565(1-3):125-31. doi: 10.1016/j.ejphar.2007.03.027. Epub 2007 Mar 24.
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.
本研究在强迫游泳试验中调查了咪唑啉受体在胍丁胺抗抑郁样效应中的作用。在强迫游泳试验中，胍丁胺（10毫克/千克，腹腔注射）的抗抑郁样效应被用依发洛新（1毫克/千克，腹腔注射，一种咪唑啉I1/α2肾上腺素能受体拮抗剂）、艾地苯醌（0.06毫克/千克，腹腔注射，一种咪唑啉I2/α2肾上腺素能受体拮抗剂）和安他唑啉（5毫克/千克，腹腔注射，一种对I2受体具有高亲和力的配体）预处理的小鼠所阻断。亚有效剂量的胍丁胺（0.001毫克/千克，腹腔注射）与可乐定（0.06毫克/千克，腹腔注射，一种咪唑啉I1/α2肾上腺素能受体激动剂）、莫索尼定（0.5毫克/千克，腹腔注射，一种咪唑啉I1/α2肾上腺素能受体激动剂）、安他唑啉（1毫克/千克，腹腔注射）和MK - 801（0.001毫克/千克，腹腔注射，一种非竞争性NMDA受体拮抗剂）产生协同抗抑郁样效应，但与依发洛新（1毫克/千克，腹腔注射）和艾地苯醌（0.06毫克/千克，腹腔注射）不产生协同效应。用育亨宾（1毫克/千克，腹腔注射，一种α2肾上腺素能受体拮抗剂）预处理小鼠可阻断胍丁胺（0.001毫克/千克，腹腔注射）与可乐定（0.06毫克/千克，腹腔注射）的协同抗抑郁样效应。亚有效剂量的MK - 801（0.001毫克/千克，腹腔注射）与安他唑啉（5毫克/千克，腹腔注射）产生协同抗抑郁样效应，但与依发洛新（1毫克/千克，腹腔注射）或艾地苯醌（0.06毫克/千克，腹腔注射）不产生协同效应。总之，本研究表明胍丁胺在强迫游泳试验中的抗不动效应取决于其与咪唑啉I1和I2受体的相互作用。
