Maki Y, Inoue T, Izumi T, Muraki I, Ito K, Kitaichi Y, Li X, Koyama T
Department of Psychiatry, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, 060-8638, Sapporo, Japan.
Eur J Pharmacol. 2000 Oct 20;406(3):411-8. doi: 10.1016/s0014-2999(00)00706-8.
The present study examined the acute anxiolytic effects of monoamine oxidase inhibitors on freezing behavior, a putative index of anxiety induced by conditioned fear stress. The selective serotonin 1A receptor agonist tandospirone (0.1-10 mg/kg) inhibited freezing dose dependently. The irreversible, non-selective monoamine oxidase inhibitors tranylcypromine (3 and 15 mg/kg) and phenelzine (30 and 80 mg/kg) reduced freezing significantly. Clorgyline (10 mg/kg, irreversible selective monoamine oxidase A inhibitor), N-(2-aminoethyl)-5-(m-fluorophenyl)-4-thiazole carboxamide (Ro 41-1049) (30 mg/kg, reversible selective monoamine oxidase A inhibitor), selegiline (3 mg/kg, irreversible selective monoamine oxidase B inhibitor) and lazabemide (10 mg/kg, reversible selective monoamine oxidase B inhibitor) had no effect on freezing behavior. However, combined administration of clorgyline (10 mg/kg) and selegiline (3 mg/kg) reduced freezing significantly, as well as combined administration of clorgyline (10 mg/kg) and lazabemide (10 mg/kg), Ro 41-1049 (30 mg/kg) and selegiline (3 mg/kg), or Ro 41-1049 (30 mg/kg) and lazabemide (10 mg/kg). These effects of monoamine oxidase inhibitors on freezing were not due to non-specific motor effects. These results suggest that acute inhibition of both monoamine oxidase A and B reduced anxiety or fear, while inhibition of monoamine oxidase A or B alone failed to reduce anxiety or fear.
本研究考察了单胺氧化酶抑制剂对僵住行为的急性抗焦虑作用，僵住行为是条件性恐惧应激诱导的焦虑的一种假定指标。选择性5-羟色胺1A受体激动剂坦度螺酮（0.1 - 10毫克/千克）剂量依赖性地抑制僵住行为。不可逆的非选择性单胺氧化酶抑制剂反苯环丙胺（3和15毫克/千克）和苯乙肼（30和80毫克/千克）显著降低僵住行为。氯吉兰（10毫克/千克，不可逆选择性单胺氧化酶A抑制剂）、N-（2-氨基乙基）-5-（间氟苯基）-4-噻唑甲酰胺（Ro 41 - 1049）（30毫克/千克，可逆选择性单胺氧化酶A抑制剂）、司来吉兰（3毫克/千克，不可逆选择性单胺氧化酶B抑制剂）和拉扎贝胺（10毫克/千克，可逆选择性单胺氧化酶B抑制剂）对僵住行为无影响。然而，氯吉兰（10毫克/千克）与司来吉兰（3毫克/千克）联合给药显著降低僵住行为，氯吉兰（10毫克/千克）与拉扎贝胺（10毫克/千克）联合给药、Ro 41 - 1049（30毫克/千克）与司来吉兰（3毫克/千克）联合给药或Ro 41 - 1049（30毫克/千克）与拉扎贝胺（10毫克/千克）联合给药也有此效果。单胺氧化酶抑制剂对僵住行为的这些作用并非由于非特异性运动效应。这些结果表明，急性抑制单胺氧化酶A和B可减轻焦虑或恐惧，而单独抑制单胺氧化酶A或B则无法减轻焦虑或恐惧。
