Rapid desensitization of the acute stimulatory effects of nicotine on rat plasma adrenocorticotropin and prolactin.
Rapid desensitization of the acute stimulatory effects of nicotine on rat plasma adrenocorticotropin and prolactin.
复制标题
DOI：
--
复制
发表时间：
1986-08
期刊：
影响因子：
--
通讯作者：
B. Sharp;H. Beyer
中科院分区：
文献类型：
--
作者：
B. Sharp;H. Beyer
尼古丁的剂量及其给药频率似乎是其对多个系统作用的基本决定因素，包括大鼠促肾上腺皮质激素（ACTH）-皮质酮和催乳素（PRL）轴的神经内分泌调节。由于在急性和慢性给药后均观察到尼古丁急性抑郁作用的脱敏，因此这些研究评估了重复给药是否会发生尼古丁对ACTH和PRL分泌的刺激作用的脱敏。广泛的剂量和时间过程实验表明，尼古丁迅速升高大鼠血浆ACTH和PRL水平，阈值剂量为0.1至0.25 mg/kg b.wt.。在PRL刺激后，水平变得显著降低。通过单剂量尼古丁（0.5 mg/kg）诱导对尼古丁对两种激素的急性刺激作用的脱敏。1小时后，尼古丁（1.0 mg/kg）未能显著刺激PRL水平，并导致ACTH适度增加。脱敏是最大的1小时后，第一次剂量，并持续至少6小时。肾上腺切除术，以消除皮质酮诱导的负反馈，并没有提高PRL反应的第二剂量的尼古丁，但它部分恢复了ACTH反应。用皮质酮预处理也未能改变PRL对单剂量尼古丁的反应，而它部分抑制了ACTH反应。尼古丁对血浆催乳素的急性刺激作用的快速脱敏与糖皮质激素负反馈无关，而促肾上腺皮质激素反应的脱敏则适度依赖。
The dose of nicotine and the frequency of its administration appear to be essential determinants of its action on multiple systems including the neuroendocrine regulation of the adrenocorticotropin (ACTH)-corticosterone and prolactin (PRL) axes in the rat. Because desensitization to the acute depressive effects of nicotine has been observed after both acute and chronic administration, these investigations assessed whether desensitization to the stimulative effects of nicotine on ACTH and PRL secretion occurs with repetitive dosing. Extensive dose and time course experiments showed that nicotine rapidly elevates rat plasma ACTH and PRL levels with a threshold dose between 0.1 to 0.25 mg/kg b.wt. i.p. After the stimulation of PRL, levels became significantly depressed. Desensitization to the acute stimulatory effects of nicotine on both hormones was induced by a single dose of nicotine (0.5 mg/kg). One hour later nicotine (1.0 mg/kg) failed to significantly stimulate PRL levels and resulted in a modest increase of ACTH. Desensitization was maximal by 1 hr after the first dose and persisted for at least 6 hr. Adrenalectomy, performed to eliminate corticosterone-induced negative feedback, did not enhance PRL responsiveness to a second dose of nicotine but it partially restored the ACTH response. Pretreatment with corticosterone also failed to modify the PRL response to a single dose of nicotine whereas it partially suppressed the ACTH response. Rapid desensitization to the acute stimulatory effects of nicotine on plasma PRL is independent of glucocorticoid negative-feedback whereas desensitization of the ACTH response is modestly dependent.