Nishikawa Hiroyuki, Inoue Takeshi, Izumi Takeshi, Nakagawa Shin, Koyama Tsukasa
Department of Psychiatry, Hokkaido University Graduate School of Medicine, Kita-ku, Sapporo, Japan.
Behav Pharmacol. 2010 Sep;21(5-6):576-9. doi: 10.1097/FBP.0b013e32833d419d.
Conditioned stress-induced freezing has been used as an indicator of anxiety in rodents to evaluate the anxiolytic effects of various compounds. However, the role of glycinergic neurotransmission in fear conditioning is not well understood. In this study, we investigated the effects of a selective glycine transporter-1 inhibitor, SSR504734, on contextual fear conditioning. In a fear acquisition experiment, rats were administered SSR504734 (3-30 mg/kg, intraperitoneal) 1 h before fear conditioning (i.e. inescapable footshock). Twenty-four hours after fear conditioning, the rats were placed in the experimental chamber without footshock, and freezing behavior was observed. SSR504734 (30 mg/kg) significantly inhibited contextual conditioned freezing. In a fear expression experiment, rats were administered SSR504734 (3-30 mg/kg, intraperitoneal) 23 h after fear conditioning and were tested 1 h after injection. SSR504734 (30 mg/kg) significantly inhibited contextual conditioned freezing. These findings indicate that SSR504734 attenuates both the acquisition and expression of contextual conditioned fear, and suggest that glycinergic neurotransmission may play an important role in conditioned fear.
条件性应激诱导的僵住反应已被用作啮齿动物焦虑的指标，以评估各种化合物的抗焦虑作用。然而，甘氨酸能神经传递在恐惧条件反射中的作用尚未得到充分理解。在本研究中，我们研究了选择性甘氨酸转运体-1抑制剂SSR504734对情境恐惧条件反射的影响。在恐惧习得实验中，大鼠在恐惧条件反射（即不可逃避的足部电击）前1小时腹腔注射SSR504734（3-30mg/kg）。恐惧条件反射24小时后，将大鼠置于无足部电击的实验箱中，观察僵住行为。SSR504734（30mg/kg）显著抑制情境性条件性僵住。在恐惧表达实验中，大鼠在恐惧条件反射后23小时腹腔注射SSR504734（3-30mg/kg），并在注射后1小时进行测试。SSR504734（30mg/kg）显著抑制情境性条件性僵住。这些发现表明，SSR504734减弱了情境性条件性恐惧的习得和表达，并提示甘氨酸能神经传递可能在条件性恐惧中起重要作用。
