Cryan John F, Bruijnzeel Adrie W, Skjei Karen L, Markou Athina
Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Psychopharmacology (Berl). 2003 Jul;168(3):347-58. doi: 10.1007/s00213-003-1445-7. Epub 2003 Apr 16.
Bupropion is an atypical antidepressant and the only non-nicotine-based therapy approved for smoking cessation. Its use has raised much debate as to how a non-nicotine-based agent can aid in smoking cessation.
We assessed the effects of bupropion on brain reward function under baseline conditions and subsequent to withdrawal from chronic nicotine administration in rats.
A discrete-trial intracranial self-stimulation paradigm procedure was used that provides one with current intensity thresholds, a measure of reward in rats under baseline conditions and subsequent to withdrawal from chronic nicotine (3.16 mg/kg per day for 7 days via osmotic minipump). Somatic signs were recorded based on a checklist of nicotine abstinence signs in animals withdrawn from nicotine.
Bupropion (10-60 mg/kg) dose-dependently lowered reward thresholds in non-withdrawing subjects indicating an increase in reward. Interestingly, a sub-effective dose of bupropion (5 mg/kg) blocked completely the threshold lowering effects of acute nicotine (0.25 mg/kg). Animals withdrawn from chronic nicotine exhibited increases in somatic signs of withdrawal and elevated brain reward thresholds, which is indicative of "diminished interest or pleasure" (i.e. anhedonia) in the rewarding stimuli. Bupropion (10-40 mg/kg) reversed both the reward deficit and the somatic signs, with the highest dose (40 mg/kg) inducing a protracted reversal of the threshold elevation.
Bupropion acts on multiple levels to alter brain reward circuits influenced by nicotine, in addition to reducing the expression of somatic signs of withdrawal. First, bupropion, unlike other antidepressants, increases brain reward function under baseline conditions in non-withdrawing subjects. Second, at low doses bupropion blocks the rewarding effects of nicotine. Third, bupropion reverses the negative affective aspects of nicotine withdrawal. Such actions are likely to act in concert to mediate the unique anti-smoking properties of bupropion.
安非他酮是一种非典型抗抑郁药，也是唯一被批准用于戒烟的非尼古丁类疗法。其使用引发了诸多关于非尼古丁类药物如何有助于戒烟的争论。
我们评估了安非他酮在基线条件下以及大鼠从慢性尼古丁给药撤药后的脑奖赏功能效应。
采用离散试验性颅内自我刺激范式程序，该程序可提供当前强度阈值，作为大鼠在基线条件下以及从慢性尼古丁（通过渗透微型泵每天3.16毫克/千克，持续7天）撤药后的奖赏指标。根据从尼古丁撤药的动物的尼古丁戒断体征清单记录躯体体征。
安非他酮（10 - 60毫克/千克）剂量依赖性地降低了未撤药受试者的奖赏阈值，表明奖赏增加。有趣的是，亚有效剂量的安非他酮（5毫克/千克）完全阻断了急性尼古丁（0.25毫克/千克）的阈值降低效应。从慢性尼古丁撤药的动物表现出戒断躯体体征增加和脑奖赏阈值升高，这表明对奖赏刺激的“兴趣或愉悦减少”（即快感缺失）。安非他酮（10 - 40毫克/千克）逆转了奖赏缺陷和躯体体征，最高剂量（40毫克/千克）诱导阈值升高的持久逆转。
安非他酮除了减少戒断躯体体征的表达外，还在多个水平上作用于改变受尼古丁影响的脑奖赏回路。首先，与其他抗抑郁药不同，安非他酮在未撤药受试者的基线条件下增加脑奖赏功能。其次，低剂量时安非他酮阻断尼古丁的奖赏效应。第三，安非他酮逆转尼古丁戒断的负面情感方面。这些作用可能协同发挥作用，介导安非他酮独特的戒烟特性。
