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自行给予和联结尼古丁均可使大鼠血压显著升高,并使心率发生变化,行为偶联仅有适度影响。

Self-administered and yoked nicotine produce robust increases in blood pressure and changes in heart rate with modest effects of behavioral contingency in rats.

机构信息

Department of Psychology, University of Pittsburgh, 210 S. Bouquet Street, Pittsburgh, PA 15260, USA.

出版信息

Pharmacol Biochem Behav. 2011 Sep;99(3):459-67. doi: 10.1016/j.pbb.2011.04.018. Epub 2011 Apr 29.

Abstract

Experimenter-administered nicotine produces reliable increases in blood pressure and changes in heart rate. However, an extensive literature demonstrates that the effects of psychoactive drugs are dependent on whether administration is contingent on behavior. The present study assessed the cardiovascular effects of nicotine and whether those effects vary as a function of whether nicotine was self-administered or response-independent. Rats were divided into three groups according to a yoked design. The pattern of infusions for each triad was determined by the animal self-administering nicotine; the other two animals received either yoked nicotine or saline. Heart rate and blood pressure were measured during eighteen daily, 1h drug sessions by radiotelemetry. Each session was preceded and followed by a 20 minute period during which cardiovascular function was monitored in the operant chambers, but drug was not available. Acute exposure to yoked nicotine produced a rapid rise in blood pressure that was larger than the increase observed with self-administered nicotine. Additional infusions during the first session resulted in a similar sustained elevation in blood pressure in the nicotine groups. Over subsequent sessions, self-administered nicotine produced a larger effect on systolic blood pressure particularly early in each session, although for both self-administered and yoked nicotine the hypertensive effects waned partially with repeated test sessions. This decrease was fully accounted for by a pre-session decrease in pressure; relative to pre-session levels the strong hypertensive effects of nicotine persisted. Initial exposure to nicotine produced a short-lived bradycardia that in subsequent sessions was replaced with a longer-lasting nicotine-induced tachycardia; neither effect was related to the behavioral contingency of nicotine delivery. Together, these data provide a rich picture of the cardiovascular effects of nicotine. Effects of behavioral contingency were observed, but differences were limited. Other non-pharmacological factors such as baseline shifts potentially related to nicotine-associated cues deserve further attention.

摘要

实验者给予尼古丁会可靠地升高血压并改变心率。然而,大量文献表明,精神活性药物的作用取决于给药是否与行为相关。本研究评估了尼古丁的心血管效应,以及这些效应是否因尼古丁是自我给药还是非依赖反应给药而有所不同。大鼠根据偶联设计分为三组。每组的输注模式由动物自我给予尼古丁决定;另外两只动物接受偶联尼古丁或盐水。通过无线电遥测术在十八个每日 1 小时的药物疗程中测量心率和血压。每个疗程之前和之后,在操作室中监测心血管功能 20 分钟,但不提供药物。急性暴露于偶联尼古丁会迅速升高血压,增幅大于自我给予尼古丁时的增幅。在第一个疗程中进行额外的输注会导致尼古丁组的血压持续升高。在随后的疗程中,自我给予尼古丁对收缩压的影响更大,特别是在每个疗程的早期,尽管对于自我给予和偶联尼古丁,随着重复的测试疗程,高血压效应会部分减弱。这种下降完全由课前血压下降引起;与课前水平相比,尼古丁的强升压作用仍然存在。最初接触尼古丁会导致短暂的心动过缓,随后会被尼古丁引起的心动过速取代;这两种效应都与尼古丁给药的行为关联性无关。这些数据提供了尼古丁心血管效应的丰富图景。观察到行为关联性的影响,但差异有限。其他非药理学因素,如与尼古丁相关线索相关的基线变化,值得进一步关注。

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