Differential modulation of feline defensive rage behavior in the medial hypothalamus by 5-HT1A and 5-HT2 receptors
Differential modulation of feline defensive rage behavior in the medial hypothalamus by 5-HT1A and 5-HT2 receptors
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DOI：
10.1016/s0006-8993(03)03036-1
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发表时间：
2003-08-15
期刊：
影响因子：
2.9
通讯作者：
Siegel, A
中科院分区：
文献类型：
--
作者：
Hassanain, M;Bhatt, S;Siegel, A
以往的研究已经证实，猫的防御性愤怒行为的表达是通过连接下丘脑内侧和中脑导水管周围灰质(PAG)背外侧象限的相互通路来调节的。本研究旨在探讨下丘脑内侧区5-HT1A和5-HT2C受体在电刺激PAG引起的防御性愤怒行为表达中的作用。单极刺激电极被放置在中脑PAG，电刺激可从PAG中诱发防御性愤怒行为。在这项研究过程中，防御性愤怒是通过测量这种行为的“嘶嘶”部分的潜伏期来确定的。将套管电极植入下丘脑内侧的部位，电刺激也可以从那里诱发防御性愤怒行为，以便稍后将5-羟色胺能化合物显微注射到下丘脑的行为可识别区域。下丘脑内侧区微量注射5-HT1a受体激动剂8-OHDPAT(0.1、1.0和3.0nmol)可剂量依赖性地抑制PAG诱发的嘶嘶声。注射5-HT1a拮抗剂p-MPPI(3.0nmol)可阻断8-OHDPAT对发声的抑制作用。8-OHDPAT的抑制作用是防御性愤怒行为所特有的，因为这种药物(3nmoL)促进了安静的咬合攻击。下丘脑内侧区微量注射5-HT2C受体激动剂(+/-)-DOI盐酸盐(0.5、1.0和3.0nmol)可促进PAG引起的嘶嘶声，并呈剂量依赖关系。这些易化作用又被选择性5-羟色胺拮抗剂LY-53,857预先阻断，LY-53,857被微量注射到下丘脑内侧部位。本研究结果表明，下丘脑内侧5-HT1a和5-HT2受体的激活对猫中脑PAG诱发的防御性愤怒行为具有不同的调节作用。(C)2003爱思唯尔B.V.保留所有权利。
Previous studies have established that the expression of defensive rage behavior in the cat is mediated over reciprocal pathways that link the medial hypothalamus and the dorsolateral quadrant of the midbrain peritaqueductal gray matter (PAG). The present study was designed to determine the roles played by 5-HT1A and 5-HT2C receptors in the medial hypothalamus on the expression of defensive rage behavior elicited from electrical stimulation of the PAG. Monopolar stimulating electrodes were placed in the midbrain PAG from which defensive rage behavior could be elicited by electrical stimulation. During the course of this study, defensive rage was determined by measuring the latency of the 'hissing' component of this behavior. Cannula-electrodes were implanted into sites within the medial hypothalamus from which defensive rage behavior could also be elicited by electrical stimulation in order that serotonergic compounds could be microinjected into behaviorally identifiable regions of the hypothalamus at a later time. Microinjections of the 5-HT1A receptor agonist 8-OHDPAT (0.1, 1.0 and 3.0 nmol) into the medial hypothalamus suppressed PAG-elicited hissing in a dose-dependent manner. Administration of the 5-HT1A antagonist p-MPPI (3.0 nmol) blocked the suppressive effects of 8-OHDPAT upon hissing. The suppressive effects of 8-OHDPAT were specific to defensive rage behavior because this drug (3 nmol) facilitated quiet biting attack. Microinjections of the 5-HT2C receptor agonist (+/-)-DOI hydrochloride into the medial hypothalamus (0.5, 1.0, and 3.0 nmol) facilitated the occurrence of PAG-elicited hissing in a dose-dependent manner. In turn, these facilitating effects were blocked by pretreatment with the selective 5-HT, antagonist, LY-53,857, which was microinjected into the same medial hypothalamic site. The findings of this study provide evidence that activation of 5-HT1A and 5-HT2 receptors within the medial hypothalamus exert differential modulatory effects upon defensive rage behavior elicited from the midbrain PAG of the cat. (C) 2003 Elsevier B.V. All rights reserved.