Lutfy Kabirullah, Brown Maria C, Nerio Namiko, Aimiuwu Otaren, Tran Benjamin, Anghel Adrian, Friedman Theodore C
Division of Endocrinology, Molecular Medicine and Metabolism, Department of Medicine, Charles R. Drew University of Medicine & Sciences-David Geffen School of Medicine at UCLA, Los Angeles, California 90059, USA.
J Neurochem. 2006 Dec;99(5):1321-7. doi: 10.1111/j.1471-4159.2006.04217.x. Epub 2006 Oct 25.
Acute nicotine administration has been shown to activate the hypothalamic-pituitary-adrenal (HPA) axis and stimulate secretion of adrenocorticotrophic hormone (ACTH), corticosterone/cortisol and beta-endorphin (beta-END) in both rodents and humans, raising the possibility that activation of the HPA axis by nicotine may mediate some of the effects of nicotine. Since stress can increase the risk of drug use and abuse, we hypothesized that repeated stress would increase the ability of nicotine to stimulate the secretion of HPA hormones. To test our hypothesis, mice were exposed to repeated stress (swimming in 15 degrees C water for 3 min/day for 5 days) and killed 15 min after injection of saline or nicotine (0.1 mg/kg, s.c.). Repeated exposure to stress increased the ability of nicotine to stimulate plasma ACTH (p<0.05) and beta-END (p<0.05), but not corticosterone secretion. In contrast, repeated exposure to stress increased the post-saline injection levels of corticosterone (p<0.05), but not ACTH and beta-END. The present results suggest that chronic stress leads to an enhanced sensitivity of some components of the HPA axis to a subsequent nicotine challenge.
急性给予尼古丁已被证明可激活下丘脑-垂体-肾上腺（HPA）轴，并刺激啮齿动物和人类体内促肾上腺皮质激素（ACTH）、皮质酮/皮质醇和β-内啡肽（β-END）的分泌，这增加了尼古丁激活HPA轴可能介导尼古丁某些作用的可能性。由于应激会增加药物使用和滥用的风险，我们推测反复应激会增强尼古丁刺激HPA激素分泌的能力。为了验证我们的假设，将小鼠暴露于反复应激（在15摄氏度水中游泳3分钟/天，持续5天），并在注射生理盐水或尼古丁（0.1毫克/千克，皮下注射）15分钟后处死。反复暴露于应激会增强尼古丁刺激血浆ACTH（p<0.05）和β-END（p<0.05）分泌的能力，但不会增强皮质酮的分泌。相反，反复暴露于应激会增加注射生理盐水后皮质酮的水平（p<0.05），但不会增加ACTH和β-END的水平。目前的结果表明，慢性应激会导致HPA轴的某些成分对随后的尼古丁刺激敏感性增强。
