Minneapolis Medical Research Foundation, 914 South 8th Street, S-3 Labs, 860, Minneapolis, MN 55404, USA.
Psychopharmacology (Berl). 2011 Sep;217(2):153-66. doi: 10.1007/s00213-011-2273-9. Epub 2011 Apr 15.
Compensatory smoking may represent an adverse consequence of smoking reduction or the use of reduced-nicotine tobacco products. Factors contributing to individual variability in compensation are poorly understood.
The objective of this study was to examine whether severity of nicotine withdrawal as measured by elevated intracranial self-stimulation (ICSS) thresholds is related to individual differences in compensatory nicotine self-administration (NSA) following unit dose reduction.
Rats were trained for ICSS and NSA (0.06 mg/kg per infusion). After stabilization, effects of reducing the nicotine unit dose to 0.03 mg/kg per infusion were examined. Following reacquisition of NSA (0.06 mg/kg per infusion), effects of antagonist-precipitated withdrawal and saline extinction (spontaneous withdrawal) were examined.
Reducing the NSA unit dose produced partial compensation as indicated by the increased infusion rates, but a 35% mean decrease in daily nicotine intake. The magnitude of compensation varied considerably among rats. Dose reduction did not elicit withdrawal in rats as a group, although there were substantial increases in ICSS thresholds in some animals. Intracranial self-stimulation thresholds were consistently elevated during precipitated and spontaneous withdrawal, confirming that rats were nicotine-dependent. Individual differences in compensation were not correlated with changes in ICSS thresholds during dose reduction, precipitated withdrawal, or spontaneous withdrawal. In a secondary analysis, greater precipitated withdrawal severity predicted greater initial nicotine seeking during extinction.
Severity of nicotine withdrawal was not related to the degree of compensation in this protocol. These data do not support a role for nicotine withdrawal in individual differences in compensation during reduced nicotine exposure, but do suggest that withdrawal may contribute to nicotine seeking during early abstinence.
补偿性吸烟可能代表了吸烟减少或使用低尼古丁烟草产品的不利后果。导致个体补偿差异的因素知之甚少。
本研究的目的是检验颅内自我刺激（ICSS）阈值升高所衡量的尼古丁戒断严重程度是否与单位剂量减少后个体尼古丁自我给药（NSA）补偿的差异有关。
大鼠接受 ICSS 和 NSA（每输注 0.06mg/kg）训练。稳定后，检查将尼古丁单位剂量减少至 0.03mg/kg/输注的效果。在 NSA（0.06mg/kg/输注）重新获得后，检查拮抗剂诱发的戒断和盐水消退（自发戒断）的效果。
减少 NSA 单位剂量产生了部分补偿，表现为输注率增加，但每日尼古丁摄入量平均减少 35%。补偿的幅度在大鼠之间差异很大。剂量减少并没有引起大鼠群体戒断，尽管一些动物的 ICSS 阈值有实质性增加。在诱发和自发戒断期间，ICSS 阈值持续升高，证实大鼠对尼古丁有依赖性。补偿的个体差异与剂量减少、诱发戒断或自发戒断期间 ICSS 阈值的变化无关。在二次分析中，诱发戒断的严重程度预测了在消退期间更大的初始尼古丁寻求。
在本方案中，尼古丁戒断的严重程度与补偿的程度无关。这些数据不支持在减少尼古丁暴露期间个体差异补偿中尼古丁戒断的作用，但确实表明戒断可能有助于早期禁欲期间的尼古丁寻求。
