Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems
Conditioned nicotine withdrawal profoundly decreases the activity of brain reward systems
复制标题
DOI：
10.1523/jneurosci.4785-04.2005
复制
发表时间：
2005-06-29
影响因子：
5.3
通讯作者：
Markou, A
中科院分区：
文献类型：
--
作者：
Kenny, PJ;Markou, A
尼古丁戒断会降低大脑奖励系统的活性，这是通过大鼠颅内自我刺激（ICSS）阈值升高来测量的。这种奖励赤字被假设为有助于烟草吸烟者的烟草习惯的持久性。越来越多的证据表明，药物戒断的各个方面可能成为条件反射，以前中性的环境刺激，通过巴甫洛夫条件反射过程。在这里，我们调查是否享乐中性刺激反复配对尼古丁戒断获得“情感价”，这样的戒断相关的条件刺激单独降低大脑的奖励功能。尼古丁依赖大鼠给予光/声条件刺激，并连续4d注射烟碱受体拮抗剂二氢-β-赤藓定（DH β E; 3 mg/kg）;在注射DH β E之前和之后立即评估ICSS阈值。在测试当天，向大鼠提供条件刺激并注射生理盐水;接下来，评估ICSS阈值。在条件反射过程中，DH β E升高了奖励阈值，并且在连续的条件反射过程中阈值升高的幅度增加。这些数据表明，戒断相关的条件刺激增强了尼古丁戒断的幅度，因为它们的动机意义增加。最重要的是，在测试当天，条件刺激单独提高了奖励阈值。同样，在另一个实验中，戒断相关的线索提高了吗啡依赖大鼠的奖励阈值。这些数据提供了第一个经验验证，条件尼古丁戒断可能发生后，暴露于戒断配对线索。此外，这些数据表明，戒断配对的条件刺激达到负的情感效价，可以降低大脑奖励系统的活动，模仿尼古丁和其他成瘾药物戒断期间观察到的奖励赤字。
Withdrawal from nicotine decreases the activity of brain reward systems, measured in rats by elevations of intracranial self-stimulation (ICSS) thresholds. This reward deficit is hypothesized to contribute to the persistence of the tobacco habit in tobacco smokers. Accumulating evidence suggests that aspects of drug withdrawal may become conditioned to previously neutral environmental stimuli via pavlovian conditioning processes. Here we investigated whether hedonically neutral stimuli repeatedly paired with nicotine withdrawal gained "affective valence" such that withdrawal-associated conditioned stimuli alone decreased brain reward function. Nicotine-dependent rats were presented with a light/tone conditioned stimulus and injected with the nicotinic receptor antagonist dihydro-beta-erythroidine (DH beta E; 3 mg/kg) for 4d consecutively; ICSS thresholds were assessed before and immediately after DH beta E injection. On the test day, the rats were presented with the conditioned stimulus and injected with saline; next, ICSS thresholds were assessed. During conditioning sessions, DH beta E elevated reward thresholds, and the magnitude by which thresholds were elevated increased during successive conditioning sessions. These data suggest that withdrawal-associated conditioned stimuli potentiated the magnitude of nicotine withdrawal as their motivational significance increased. Most importantly, on the test day, the conditioned stimulus alone elevated reward thresholds. Similarly, in a separate experiment, withdrawal-associated cues elevated reward thresholds in morphine-dependent rats. These data provide the first empirical verification that conditioned nicotine withdrawal may occur after exposure to withdrawal-paired cues. Moreover, these data demonstrate that withdrawal-paired conditioned stimuli attain negative affective valence and can decrease the activity of brain reward systems, mimicking the reward deficit observed during withdrawal from nicotine and other addictive drugs.