Chronic bupropion attenuated the anhedonic component of nicotine withdrawal in rats via inhibition of dopamine reuptake in the nucleus accumbens shell
Chronic bupropion attenuated the anhedonic component of nicotine withdrawal in rats via inhibition of dopamine reuptake in the nucleus accumbens shell
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DOI：
10.1111/j.1460-9568.2007.05546.x
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发表时间：
2007-05-01
影响因子：
3.4
通讯作者：
Markou, Athina
中科院分区：
文献类型：
--
作者：
Paterson, Neil E.;Balfour, David J.;Markou, Athina
安非他酮是一种多巴胺再摄取抑制剂，是一种有效的戒烟治疗方法，但介导其戒烟特性的行为和神经化学机制相对未知。为了探讨安非他酮通过多巴胺依赖性机制部分改善尼古丁戒断的假设，我们研究了慢性安非他酮对尼古丁戒断大鼠延髓核壳钾刺激多巴胺溢出的影响。我们还评估了慢性安非他酮对尼古丁戒断行为方面的影响，通过提高大脑奖励阈值和戒断的躯体体征来测量。用尼古丁或盐水处理大鼠7天，然后开始同时给予安非他酮或盐水。安非他酮/生理盐水和尼古丁/生理盐水联合给药14天后，尼古丁/生理盐水给药终止，而安非他酮/生理盐水给药继续。这些条件模拟人类吸烟者中的安非他酮给药。在非安非他酮处理的大鼠中停止尼古丁给药升高了奖励阈值，反映了奖励不足，增加了躯体体征，减少了钾诱发的多巴胺溢出在丘脑核壳中。慢性安非他酮降低奖励阈值和增加钾诱发的多巴胺释放，无论以前的尼古丁暴露，可能是通过抑制多巴胺再摄取，从而减弱尼古丁戒断的快感缺乏和神经化学作用。慢性安非他酮阻断戒断相关的躯体体征增加。最后，急性实验者管理的尼古丁增强大脑奖励功能，同样在所有组，表明安非他酮不会改变奖励促进实验者管理的尼古丁的影响。总之，安非他酮诱导的增加细胞外多巴胺的核壳可以改善与尼古丁戒断相关的快感缺失，这反过来又可能有助于戒烟。
Bupropion, a dopamine reuptake inhibitor, is an effective therapy for smoking cessation, but the behavioral and neurochemical mechanisms mediating its antismoking properties are relatively unknown. To explore the hypothesis that bupropion ameliorates nicotine withdrawal partly by a dopamine-dependent mechanism, we investigated the effects of chronic bupropion on potassium-stimulated dopamine overflow in the nucleus accumbens shell in nicotine-withdrawing rats. We also assessed the effects of chronic bupropion on behavioral aspects of nicotine withdrawal measured by elevations in brain reward thresholds and somatic signs of withdrawal. Rats were treated with nicotine or saline for 7 days and then coadministration of bupropion or saline was initiated. After 14 days of coadministration of bupropion/saline and nicotine/saline, nicotine/saline administration was terminated, whereas bupropion/saline administration continued. These conditions mimic bupropion administration in human smokers. Cessation of nicotine administration in non-bupropion-treated rats elevated reward thresholds reflecting a reward deficit, increased somatic signs and diminished potassium-evoked dopamine overflow in the nucleus accumbens shell. Chronic bupropion lowered reward thresholds and increased potassium-evoked dopamine release regardless of previous nicotine exposure, possibly by inhibition of dopamine reuptake, and thus attenuated the anhedonic and neurochemical effects of nicotine withdrawal. Chronic bupropion blocked withdrawal-associated increased somatic signs. Finally, acute experimenter-administered nicotine enhanced brain reward function equally in all groups, indicating that bupropion does not alter the reward-facilitating effects of experimenter-administered nicotine. In conclusion, the bupropion-induced increase in extracellular dopamine in the nucleus accumbens shell may ameliorate the anhedonia associated with nicotine withdrawal, which in turn may facilitate smoking cessation.