The role of corticosteroids in nicotine's physiological and behavioral effects
The role of corticosteroids in nicotine's physiological and behavioral effects
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DOI：
10.1016/s0306-4530(97)00078-4
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发表时间：
1998-02-01
影响因子：
3.7
通讯作者：
Perkins, KA
中科院分区：
文献类型：
--
作者：
Caggiula, AR;Donny, EC;Perkins, KA
本文回顾了表明肾上腺皮质类固醇调节小鼠和大鼠对尼古丁反应性的证据。肾上腺切除术增加，急性和慢性皮质类固醇给药减少，尼古丁的一些生理和行为影响。肾上腺类固醇的功能之一可能是调节压力引起的尼古丁敏感性变化。另一种方法是，当间歇性地给予尼古丁并且所产生的耐受性具有后天习得的成分时，可以调节慢性耐受性的发展。研究结果表明，糖皮质激素在尼古丁耐受性发展中的作用是，血浆皮质酮的条件性升高（预期尼古丁的输送）伴随着慢性耐受性的发展，并且环境因素会诱发条件性皮质酮反应，但只有在它们与尼古丁输送相关之后。尽管最近的体外证据表明类固醇可以快速且可逆地降低烟碱受体功能，但肾上腺类固醇调节尼古丁敏感性的机制尚不清楚。虽然大多数数据与皮质类固醇降低尼古丁反应性，从而促进习得的耐受性的假设一致，但有新的发现表明，皮质类固醇会增加对尼古丁运动激活作用的敏感性的发展。这些数据表明，假设皮质类固醇对尼古丁作用具有单向作用（例如敏感性降低）的配方必须进行修改，以考虑相互作用的变量，例如正在研究的特定尼古丁效应以及该效应通常是否表现出耐受性或致敏性。最后，研究表明，先前报道的实验者给药药物的尼古丁升高皮质酮的作用，在尼古丁给药取决于操作反应并且维持尼古丁自我给药发展的剂量时也会产生。这些发现强调了在未来探索肾上腺类固醇与尼古丁功能之间的关系中使用自我给药模型的可行性。 (C) 1998 Elsevier Science Ltd. 保留所有权利。
This paper reviews evidence indicating that adrenal corticosteroids modulate the responsiveness of mice and rats to nicotine. Adrenalectomy increases, and both acute and chronic corticosteroid administration decrease, some of the physiological and behavioral effects of nicotine. One function of adrenal steroids may be to regulate stress-induced changes in nicotine sensitivity. Another is to mediate the development of chronic tolerance when nicotine is given intermittently, and when the resulting tolerance has a learned component. A role of glucocorticoids in the development of tolerance to nicotine is suggested by the findings that a conditioned elevation of plasma corticosterone, which anticipates nicotine delivery, accompanies the development of chronic tolerance and that environmental cues evoke a conditioned corticosterone response, but only after they have become associated with nicotine delivery. The mechanisms by which adrenal steroids modulate nicotine sensitivity are not known, although recent in vitro evidence suggests that steroids can rapidly and reversibly reduce nicotinic receptor function. While most of the data are consistent with the hypothesis that corticosteroids reduce nicotine responsiveness, and thus promote a learned form of tolerance, there are new findings that corticosteroids increase the development of sensitization to the locomotor-activating effects of nicotine. These data suggest that formulations postulating a unidirectional effect of corticosteroids on nicotine's actions (e.g. decreased sensitivity) must be revised to take into account interacting variables such as the specific nicotine effect being studied and whether that effect normally exhibits tolerance or sensitization. Finally, research is presented which indicates that the corticosterone-elevating effects of nicotine, previously reported for experimenter-administered drug, are also produced when nicotine administration is contingent on an operant response, and at a dose which sustains the development of nicotine self-administration in rats. These findings highlight the feasibility of using self-administration models in future explorations of the relationship between adrenal steroids and nicotine function. (C) 1998 Elsevier Science Ltd. All rights reserved.