Department of Psychology, University of Minnesota, 75 East River Rd, Minneapolis, MN 55455, USA.
Psychopharmacology (Berl). 2009 Nov;207(1):13-25. doi: 10.1007/s00213-009-1632-2. Epub 2009 Aug 11.
Elevated acoustic startle amplitude has been used to measure anxiety-like effects of drug withdrawal in humans and animals. Withdrawal from a single opiate administration has been shown to produce robust elevations in startle amplitude ("withdrawal-potentiated startle") that escalate in severity with repeated exposure. Although anxiety is a clinical symptom of nicotine dependence, it is currently unknown whether anxiety-like behavior is elicited during the early stages of nicotine dependence in rodents.
The objective of this study is to examine whether, as is the case with opiates, single or repeated exposure to nicotine can produce withdrawal-potentiated startle.
Rats received daily nicotine injections for 14 days, and startle amplitude was tested during spontaneous withdrawal on injection days 1, 7, and 14.
Elevated startle responding was observed during nicotine withdrawal on days 7 and 14 but not on day 1, was greater at higher nicotine doses, and was reduced by a nicotine replacement injection given during an additional test session on day 15. Additional experiments demonstrated that nicotine withdrawal-potentiated startle was reduced by the alpha(2)-adrenergic agonist clonidine and that precipitated withdrawal-potentiated startle could not be induced by injection of the nicotinic acetylcholine receptor antagonist mecamylamine.
These results suggest that nicotine withdrawal escalates in severity across days, similar to the previously reported escalation of opiate withdrawal-potentiated startle. Potentiated startle may be a reliable measure of withdrawal from different classes of abused drugs and may be useful in the study of the early stages of drug dependence.
在人类和动物中，升高的听觉惊跳幅度被用于测量药物戒断引起的类焦虑效应。单次阿片类药物戒断已被证明会产生显著的惊跳幅度升高（“戒断增强的惊跳”），随着重复暴露，其严重程度会逐渐加剧。尽管焦虑是尼古丁依赖的一种临床症状，但目前尚不清楚在啮齿类动物的尼古丁依赖早期阶段是否会引起类焦虑行为。
本研究的目的是检验，与阿片类药物一样，单次或重复接触尼古丁是否会导致戒断增强的惊跳。
大鼠接受每日尼古丁注射 14 天，在注射日第 1、7 和 14 天进行自发戒断期间测试惊跳幅度。
在第 7 和 14 天的尼古丁戒断期间观察到惊跳反应升高，但在第 1 天没有升高，在较高尼古丁剂量下升高更明显，并且在第 15 天的另一次测试期间给予尼古丁替代注射会降低升高的惊跳反应。进一步的实验表明，尼古丁戒断增强的惊跳反应被α2-肾上腺素能激动剂可乐定降低，而注射烟碱型乙酰胆碱受体拮抗剂美加明不能引起戒断增强的惊跳反应。
这些结果表明，尼古丁戒断在数天内逐渐加重，类似于先前报道的阿片类药物戒断增强的惊跳反应的加重。增强的惊跳反应可能是评估不同滥用药物戒断的可靠指标，可能有助于研究药物依赖的早期阶段。
