普萘洛尔、可乐定和哌唑嗪对大鼠尼古丁戒断时脑奖赏阈提高和躯体征象的影响。
Effects of prazosin, clonidine, and propranolol on the elevations in brain reward thresholds and somatic signs associated with nicotine withdrawal in rats.
机构信息
Department of Psychiatry, McKnight Brain Institute, University of Florida, 100 S. Newell Dr., P.O. Box 100256, Gainesville, FL 32610, USA.
出版信息
Psychopharmacology (Berl). 2010 Dec;212(4):485-99. doi: 10.1007/s00213-010-1970-0. Epub 2010 Aug 10.
RATIONALE
Tobacco withdrawal is characterized by a negative mood state and relatively mild somatic symptoms. Increased noradrenergic transmission has been reported to play an important role in opioid withdrawal, but little is known about the role of noradrenergic transmission in nicotine withdrawal.
OBJECTIVES
The aim of these experiments was to investigate the effects of prazosin, clonidine, and propranolol on the negative mood state and somatic signs associated with nicotine withdrawal in rats.
METHODS
A discrete-trial intracranial self-stimulation procedure was used to assess the negative affective state of nicotine withdrawal. Elevations in brain reward thresholds are indicative of a deficit in brain reward function.
RESULTS
In all the experiments, the nicotinic acetylcholine receptor antagonist mecamylamine (3 mg/kg) elevated the brain reward thresholds of the nicotine-treated rats and did not affect those of the control rats. The α1-adrenergic receptor antagonist prazosin (0.0625 and 0.125 mg/kg) dose-dependently attenuated the elevations in brain reward thresholds associated with precipitated nicotine withdrawal. The α2-adrenergic receptor agonist clonidine (10-40 μg/kg) and the nonselective β-adrenergic receptor antagonist propranolol (2.5-10 mg/kg) did not attenuate the elevations in brain reward thresholds associated with nicotine withdrawal. Furthermore, mecamylamine (2 mg/kg) induced more somatic signs in the nicotine-treated rats than in the control rats. Clonidine and propranolol, but not prazosin, decreased the total number of somatic signs associated with nicotine withdrawal.
CONCLUSION
Blockade of α1-adrenergic receptors attenuates the deficit in brain reward function associated with nicotine withdrawal. Antagonism of β-adrenergic receptors or stimulation of α2-adrenergic receptors attenuates the somatic symptoms of nicotine withdrawal.
理由
烟草戒断的特征是负面情绪状态和相对轻微的躯体症状。据报道，去甲肾上腺素能传递增加在阿片戒断中起重要作用，但关于去甲肾上腺素能传递在尼古丁戒断中的作用知之甚少。
目的
这些实验的目的是研究普萘洛尔、可乐定和哌唑嗪对大鼠尼古丁戒断相关负面情绪状态和躯体症状的影响。
方法
采用离散试验颅内自我刺激程序来评估尼古丁戒断的负面情绪状态。大脑奖赏阈值升高表明大脑奖赏功能缺陷。
结果
在所有实验中，烟碱型乙酰胆碱受体拮抗剂美加明（3mg/kg）升高了尼古丁处理大鼠的大脑奖赏阈值，而对对照大鼠的大脑奖赏阈值没有影响。α1-肾上腺素能受体拮抗剂哌唑嗪（0.0625 和 0.125mg/kg）剂量依赖性地减轻了与诱发尼古丁戒断相关的大脑奖赏阈值升高。α2-肾上腺素能受体激动剂可乐定（10-40μg/kg）和非选择性β-肾上腺素能受体拮抗剂普萘洛尔（2.5-10mg/kg）不能减轻与尼古丁戒断相关的大脑奖赏阈值升高。此外，美加明（2mg/kg）在尼古丁处理的大鼠中引起的躯体症状比在对照大鼠中更多。可乐定和普萘洛尔，但不是哌唑嗪，减少了与尼古丁戒断相关的总躯体症状数。
结论
阻断α1-肾上腺素能受体可减轻与尼古丁戒断相关的大脑奖赏功能缺陷。β-肾上腺素能受体拮抗剂或α2-肾上腺素能受体刺激可减轻尼古丁戒断的躯体症状。
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