Hippocampal serotonergic system is involved in anxiety-like behavior induced by corticotropin-releasing factor
Hippocampal serotonergic system is involved in anxiety-like behavior induced by corticotropin-releasing factor
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DOI：
10.1016/j.brainres.2003.08.021
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发表时间：
2003-11-21
期刊：
影响因子：
2.9
通讯作者：
Watanabe, S
中科院分区：
文献类型：
--
作者：
Kagamiishi, Y;Yamamoto, T;Watanabe, S
为了阐明促肾上腺皮质激素释放因子（CRF）和5-HT系统产生的焦虑样行为之间的相互作用，我们研究了侧脑室（i. c. v.）在升高的十字迷宫表现上施用CPF作为焦虑的指标，在大鼠中使用体内脑透析方法测量腹侧海马中5-HT的细胞外水平。CRF（0.3-1.0 μ g/大鼠）给药后，迷宫开放臂中花费的时间和开放臂进入次数以剂量依赖性方式减少。通过使用5-HT 1A受体激动剂8-OH-DPAT（0.5 mg/kg，皮下注射）预处理可以预防CRF的这些作用。在生化研究中，CRF使腹侧海马体中5-HT释放增加约150-250%，高于基线，并且这种升高被CRF受体拮抗剂α-螺旋CRF 9 -41（50 μ g/大鼠）和5-HT 1A受体激动剂8-OH-DPAT（0.5 mg/kg，s.c.）显著抑制。这些结果提示CRF产生的焦虑样效应可能与腹侧海马5-HT传递增加有关。采取与证据CRF高分泌的抑郁症和焦虑相关的疾病患者，我们的研究结果导致一个有趣的假设，CPF和5-HT之间的相互作用，特别是在腹侧海马，在情感和焦虑障碍的病因中发挥作用。(C)2003 Elsevier B. V.保留所有权利。
To clarify the interaction between anxiety-like behavior produced by corticotropin-releasing factor (CRF) and the 5-HT system, we investigated the effects of intracerebroventricular (i.c.v.) administration of CPF on an elevated plus-maze performance as indices of anxiety, measuring extracellular levels of 5-HT in the ventral hippocampus using an in vivo brain dialysis method in rats. The time spent in the open arms of the maze and the number of open arm entries were decreased in a dose-dependent manner by the administration of CRF (0.3-1.0 mug/ rat). These effects of CRF were prevented by pretreatment with a 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, s.c.). In biochemical studies, CRF increased 5-HT release about 150-250% above baseline in the ventral hippocampus and this elevation was significantly inhibited by a CRF receptor antagonist, alpha-Helical CRF9-41 (50 mug/rat), and 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, s.c.). These results suggested that the anxiety-like effect produced by CRF may have involved increased 5-HT transmission in the ventral hippocampus. Taken with the evidence for hypersecretion of CRF in patients with depression and anxiety-related disorders, our findings lead to the intriguing hypothesis that interaction between CPF and 5-HT, especially in the ventral hippocampus, plays a role in the etiology of affective and anxiety disorders. (C) 2003 Elsevier B.V. All rights reserved.