Oliver Jason A, Evans David E, Addicott Merideth A, Potts Geoffrey F, Brandon Thomas H, Drobes David J
Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC.
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, FL.
Nicotine Tob Res. 2017 Jun 1;19(6):686-693. doi: 10.1093/ntr/ntx067.
Nicotine withdrawal reduces neurobiological responses to nonsmoking rewards. Insight into these reward deficits could inform the development of targeted interventions. This study examined the effect of withdrawal on neural and behavioral responses during a reward prediction task.
Smokers (N = 48) attended two laboratory sessions following overnight abstinence. Withdrawal was manipulated by having participants smoke three regular nicotine (0.6 mg yield; satiation) or very low nicotine (0.05 mg yield; withdrawal) cigarettes. Electrophysiological recordings of neural activity were obtained while participants completed a reward prediction task that involved viewing four combinations of predictive and reward-determining stimuli: (1) Unexpected Reward; (2) Predicted Reward; (3) Predicted Punishment; (4) Unexpected Punishment. The task evokes a medial frontal negativity that mimics the phasic pattern of dopaminergic firing in ventral tegmental regions associated with reward prediction errors.
Nicotine withdrawal decreased the amplitude of the medial frontal negativity equally across all trial types (p < .001). Exploratory analyses indicated withdrawal increased time to initiate the next trial following unexpected punishment trials (p < .001) and response time on reward trials during withdrawal was positively related to nicotine dependence (p < .001).
Nicotine withdrawal had equivocal impact across trial types, suggesting reward processing deficits are unlikely to stem from changes in phasic dopaminergic activity during prediction errors. Effects on tonic activity may be more pronounced. Pharmacological interventions directly targeting the dopamine system and behavioral interventions designed to increase reward motivation and responsiveness (eg, behavioral activation) may aid in mitigating withdrawal symptoms and potentially improving smoking cessation outcomes.
Findings from this study indicate nicotine withdrawal impacts reward processing signals that are observable in smokers' neural activity. This may play a role in the subjective aversive experience of nicotine withdrawal and potentially contribute to smoking relapse. Interventions that address abnormal responding to both pleasant and unpleasant stimuli may be particularly effective for alleviating nicotine withdrawal.
尼古丁戒断会降低对非吸烟奖励的神经生物学反应。深入了解这些奖励缺陷可为有针对性的干预措施的开发提供信息。本研究考察了戒断对奖励预测任务期间神经和行为反应的影响。
吸烟者（N = 48）在过夜戒烟后参加两次实验室实验。通过让参与者吸食三支常规尼古丁（0.6毫克产量；饱腹）或极低尼古丁（0.05毫克产量；戒断）香烟来控制戒断状态。在参与者完成一项奖励预测任务时，记录神经活动的电生理数据，该任务涉及观看预测性和奖励决定性刺激的四种组合：（1）意外奖励；（2）预测奖励；（3）预测惩罚；（4）意外惩罚。该任务会引发内侧额叶负波，模拟与奖励预测误差相关的腹侧被盖区多巴胺能放电的相位模式。
尼古丁戒断在所有试验类型中均同等程度地降低了内侧额叶负波的幅度（p <.001）。探索性分析表明，戒断增加了意外惩罚试验后开始下一次试验的时间（p <.001），并且戒断期间奖励试验的反应时间与尼古丁依赖呈正相关（p <.001）。
尼古丁戒断对不同试验类型的影响不明确，这表明奖励处理缺陷不太可能源于预测误差期间相位多巴胺能活动的变化。对紧张性活动的影响可能更明显。直接针对多巴胺系统的药物干预和旨在增加奖励动机和反应性的行为干预（例如行为激活）可能有助于减轻戒断症状并潜在改善戒烟结果。
本研究结果表明，尼古丁戒断会影响吸烟者神经活动中可观察到的奖励处理信号。这可能在尼古丁戒断的主观厌恶体验中起作用，并可能导致吸烟复发。针对对愉快和不愉快刺激的异常反应的干预措施可能对减轻尼古丁戒断特别有效。
