CORTICOTROPIN-RELEASING FACTOR INDUCES A PLACE AVERSION INDEPENDENT OF ITS NEUROENDOCRINE ROLE

CORTICOTROPIN-RELEASING FACTOR INDUCES A PLACE AVERSION INDEPENDENT OF ITS NEUROENDOCRINE ROLE
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DOI:
10.1016/0006-8993(92)91487-y
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发表时间:
1992-12-04
期刊:
影响因子:
2.9
通讯作者:
STINUS, L
STINUS, L
中科院分区:
医学3区
文献类型:
--
作者:
CADOR, M;AHMED, SH;STINUS, L

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本实验的目的是验证一种假设,即促肾上腺皮质激素释放因子(CRF),一种由41个氨基酸组成的多肽,在脑室内(i.c.v)或皮下(s.c)给药时,在条件位置偏好范式中具有厌恶特性。试验了5个剂量的CRF(0、0.005、0.05、0.5、5马克杯)。icc.v CRF诱导了一种特定的剂量依赖性减少,减少了在环境中花费的时间,这种减少与先前的CRF管理相匹配。此外,我们还研究了一种特殊的CRF拮抗剂α -螺旋CRF(9-41)的预处理对CRF诱导的场所厌恶的抑制作用。为了验证CRF诱导的厌恶效应是否可能是由注射CRF时刺激HPA轴引起的,我们在相同的剂量范围内研究了CRF的增强特性。只有高剂量的s.c.在产生地方厌恶上是有效的,这表明CRF的厌恶效应不可能仅仅是由于刺激了垂体-肾上腺皮质系统(通过血浆促肾上腺皮质激素(ACTH)和皮质酮水平来测量),因为低剂量持续激活垂体-肾上腺皮质系统而不产生任何行为改变。总之,这些数据表明非神经分泌性CRF神经元可能介导应激时发生的厌恶状态。
The purpose of the present experiment was to test the hypothesis that corticotropin-releasing factor (CRF), a polypeptide of 41 amino acids, when administered either intracerebroventricularly (i.c.v.) or subcutaneously (s.c.), has aversive properties in the conditioned place-preference paradigm. Five doses of CRF (0, 0.005, 0.05, 0.5, 5 mug) were tested. i.c.v. CRF induced a specific dose-dependent reduction of the amount of time spent in the environment previously paired with the administration of CRF. Furthermore, this CRF-induced place aversion was prevented by pretreatment with alpha-helical-CRF(9-41), a specific CRF antagonist, administered i.c.v. In order to test whether the aversive effects induced by i.c.v. CRF could result from the stimulation of the HPA axis accompanying i.c.v. CRF injection, the reinforcing properties of s.c. CRF were studied using the same dose range. Only the higher s.c. dose was effective in producing a place aversion suggesting that the aversive effects of CRF could not be due solely to the stimulation of the pituitary-adrenocortical system, measured by plasmatic levels of adrenocorticotropic hormone (ACTH) and corticosterone, because the lower doses consistently activate the pituitary-adrenocortical system without producing any behavioral changes. Altogether, these data indicate that the non-neurosecretory CRF neurons may mediate the aversive state occurring during stress.