纳曲酮对酒精觅药和饮酒的目标导向和习惯性模型的特异性和非特异性作用。
Specific and nonspecific effects of naltrexone on goal-directed and habitual models of alcohol seeking and drinking.
机构信息
Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC 27599-7178, USA.
出版信息
Alcohol Clin Exp Res. 2013 Jul;37(7):1100-10. doi: 10.1111/acer.12081. Epub 2013 Feb 7.
BACKGROUND
The opioid-receptor antagonist naltrexone (NTX) reduces goal-directed alcohol drinking in rats presumably by blunting alcohol reward. However, different operant conditioning behavior can be produced by different reinforcement schedules, with goal-directed operant behavior being more sensitive to changes in reward value than less flexible, habit-associated models. We tested the hypothesis that NTX more effectively reduces alcohol drinking and seeking in a goal-directed than in a habit-associated operant model, and more effectively reduces alcohol versus sucrose self-administration, consistent with diminished alcohol reward.
METHODS
Rats were trained to self-administer 10% alcohol or 1.5% sucrose in a lever-press task and then underwent a within-subject assessment of NTX (0.1 to 1 mg/kg) effects on operant behavior. A fixed-ratio (FR5) reinforcement schedule was used to model goal-directed behavior, and a variable-interval (VI30) schedule was used to model habitual behavior.
RESULTS
As predicted, NTX reduced fluid deliveries earned by the FR5-alcohol group significantly more than all other groups. However, NTX reduced lever presses during self-administration sessions in VI30-trained rats without reducing earned deliveries, due to the low contingency between rate of pressing and fluid deliveries under that schedule. Interestingly, when fluid delivery was withheld (extinction), NTX reduced reward-seeking in all rats. Finally, NTX blocked reinstatement of reward-seeking upon presentation of 0.2 ml alcohol or sucrose and associated cues in the FR5-trained but not VI30-trained rats.
CONCLUSIONS
NTX reduced goal-directed alcohol drinking compared with other operant conditions. In addition, NTX blocked reinstatement of reward-seeking in rats trained on the goal-directed FR5 reinforcement schedule but not in rats trained on the habit-like VI30 reinforcement schedule. However, NTX also exerted nonspecific effects on reward-seeking that were revealed under low-effort contingency conditions or absence of reward. Together, these data support the hypothesis that NTX is less effective in conditioning models that are more habit-associated.
背景
阿片受体拮抗剂纳曲酮（NTX）通过削弱酒精奖赏来减少大鼠的目标导向性饮酒。然而，不同的操作性条件反射行为可以通过不同的强化方案产生，目标导向性操作性行为比灵活性较低、与习惯相关的模型对奖赏价值的变化更为敏感。我们测试了这样一个假设，即 NTX 能更有效地减少目标导向性而非习惯相关操作性模型中的酒精摄入和寻求，并且更有效地减少酒精而不是蔗糖的自我给药，这与酒精奖赏的减弱一致。
方法
大鼠被训练在压杆任务中自我给予 10%酒精或 1.5%蔗糖，然后进行 NTX（0.1 至 1mg/kg）对操作性行为影响的个体内评估。使用固定比率（FR5）强化方案来模拟目标导向性行为，使用可变间隔（VI30）方案来模拟习惯性行为。
结果
正如预测的那样，NTX 显著减少了 FR5-酒精组的液体输送量，比其他所有组都多。然而，NTX 减少了 VI30 训练大鼠在自我给药期间的压杆次数，而没有减少获得的输送量，这是由于在该方案下按压率和液体输送量之间的低关联。有趣的是，当液体输送被取消（消退）时，NTX 减少了所有大鼠的奖励寻求。最后，NTX 阻止了在 FR5 训练大鼠中呈现 0.2ml 酒精或蔗糖以及相关线索时奖励寻求的复燃，但在 VI30 训练大鼠中没有阻止。
结论
NTX 减少了与其他操作性条件相比的目标导向性饮酒。此外，NTX 阻断了在目标导向性 FR5 强化方案训练的大鼠中奖励寻求的复燃，但在在习惯样 VI30 强化方案训练的大鼠中没有阻断。然而，NTX 也对在低努力关联条件下或缺乏奖励时出现的奖励寻求产生了非特异性影响。总的来说，这些数据支持了这样一个假设，即 NTX 在与习惯相关的模型中效果较差。
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