The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801
The opposite effect of a low and a high dose of serotonin-1A agonist on behavior induced by MK-801
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DOI：
10.1016/j.neuropharm.2006.11.004
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发表时间：
2007-03-01
影响因子：
4.7
通讯作者：
Horacek, Jiri
中科院分区：
文献类型：
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作者：
Bubenikova-Valesova, Vera;Votava, Martin;Horacek, Jiri
本研究的目的是探讨突触前和突触后血清素 1A (5-HT1A) 受体对 NMDA 受体非竞争性拮抗剂地佐环平 (MK-801) 诱导的精神病样行为的相反作用。 雄性 Wistar 大鼠接受两剂（0.025 mg/kg 和 1 mg/kg）5-HT1A 受体激动剂 8-OH-DPAT (8-羟基-2-(二正丙氨基)四氢化萘)和/或MK-801，两种不同剂量，0.1mg/kg或0.3mg/kg。我们通过测试大鼠声惊吓反应 (PPI) 和运动活动的前脉冲抑制来测量感觉运动门控。我们发现低和高 5-HT1A 受体激动剂剂量对 MK-801 诱导的习惯性大鼠 PPI 缺陷和运动过度产生相反的作用。低剂量的 8-OH-DPAT 优先作用于突触前 5-HT1A 受体，恢复了 MK-801 (0.1 mg/kg) 治疗的习惯大鼠的 PPI 缺陷和过度运动。然而，高剂量的 8-OH-DPAT 可激活突触前和突触后 5-HT1A 受体，在给予低剂量 MK-801 后，可降低 PPI 并增加运动活性。施用 8-OH-DPAT 本身可剂量依赖性地降低 PPI。然而，只有高剂量的8-OH-DPAT才能增加大鼠的自发运动活动。我们的结果表明NMDA和5-HT1A受体之间存在相互作用。此外，这些发现可能表明，5-HT1A 自身受体的激活可以有效治疗精神分裂症，但受体的完全有效激动可能会使精神病症状恶化。 (c) 2006 Elsevier Ltd. 保留所有权利。
The purpose of the present study was to investigate the opposite effect of the pre- and postsynaptic serotonin-1A (5-HT1A) receptors on the psychotic-like behavior induced by a non-competitive antagonist of the NMDA receptor, dizocilpine (MK-801).Male Wistar rats received two doses (0.025 mg/kg and 1 mg/kg) of 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino) tetralin) and/or MK-801 in two different doses, 0.1 mg/kg or 0.3 mg/kg. We measured sensorimotor gating by testing prepulse inhibition of acoustic startle response (PPI) and locomotor activity of rats.We found an opposite effect of the low and high 5-HT1A receptor agonist doses on MK-801 induced deficit in PPI and hyperlocomotion in habituated rats. The low dose of 8-OH-DPAT, which preferentially acts on presynaptic 5-HT1A receptors, restored the deficit in PPI and hyperlocomotion in MK-801 (0.1 mg/kg)-treated habituated rats. However, the high dose of 8-OH-DPAT, which activates both pre- and postsynaptic 5-HT1A receptors, decreased PPI and increased locomotor activity after administration of the low dose of MK-801. Administration of 8-OH-DPAT itself dose-dependently decreased PPI. However, only the high dose of 8-OH-DPAT increased spontaneous locomotor activity of rats.Our results indicate that there is an interaction between the NMDA and 5-HT1A receptors. In addition, these findings could indicate that activation of the 5-HT1A autoreceptor could be effective as a treatment in schizophrenia, but full potent agonism of the receptor could worsen the psychotic symptoms. (c) 2006 Elsevier Ltd. All rights reserved.