Clozapine reduces nicotine self-administration, blunts reinstatement of nicotine-seeking but increases responding for food
Clozapine reduces nicotine self-administration, blunts reinstatement of nicotine-seeking but increases responding for food
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DOI：
10.1111/adb.12619
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发表时间：
2019-07-01
影响因子：
3.4
通讯作者：
Fletcher, Paul J.
中科院分区：
文献类型：
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作者：
Abela, Andrew R.;Li, Zhaoxia;Fletcher, Paul J.
精神分裂症患者的吸烟率明显高于普通人群，这可能是由于尼古丁和抗精神病药物之间的相互作用所致。虽然传统抗精神病药物氟哌啶醇有时会增加精神分裂症患者的吸烟量，但有一些证据表明氯氮平（一种非典型抗精神病药物）可能会减少这些患者的尼古丁使用。然而，氯氮平等抗精神病药物对尼古丁自我给药和恢复的影响尚未得到系统研究。在本研究中，我们评估了在固定比例和渐进比例强化方案下，以及在戒断一段时间后恢复尼古丁寻求时，氯氮平对尼古丁自我给药的影响。为了确定其对尼古丁奖励影响的特异性，我们还测试了氯氮平在固定比例和渐进比例方案下对食物强化反应的影响。为了进行比较，我们还检查了氟哌啶醇（一种第一代抗精神病药物）在与氯氮平相同的行为条件下的作用。我们发现氯氮平可以抑制尼古丁的自我给药和尼古丁寻求的恢复，但也会增加大鼠为获得食物奖励而付出的努力。相比之下，大范围剂量的氟哌啶醇减弱了对尼古丁和食物奖励的反应，表明强化剂功效的非特异性降低。这些结果表明，氯氮平除了具有抗精神病特性外，还具有作为精神分裂症患者戒烟治疗的潜在用途。
People with schizophrenia display significantly higher rates of smoking than the general population, which may be due to an interaction between nicotine and antipsychotic medication. While the conventional antipsychotic drug haloperidol sometimes increases cigarette smoking in patients with schizophrenia, there is some evidence suggesting that clozapine, an atypical antipsychotic drug, may reduce nicotine use in these patients. However, the effects of antipsychotic drugs like clozapine on aspects of nicotine self-administration and reinstatement have not been systematically examined. In the current study, we assessed the effect of clozapine on nicotine self-administration under fixed ratio and progressive ratio schedules of reinforcement, as well as reinstatement of nicotine-seeking following a period of abstinence. To determine the specificity of its effect on nicotine reward, we also tested the effect of clozapine on responding for food reinforcement under fixed ratio and progressive ratio schedules. For comparison, we also examined the effects of haloperidol, a first-generation antipsychotic drug, under some of the same behavioral conditions as clozapine. We show that clozapine inhibits nicotine self-administration and reinstatement of nicotine-seeking but also increases the amount of effort that rats will exert for food reward. In contrast, haloperidol at a wide range of doses attenuated responding for nicotine and food reward, suggestive of a non-specific reduction in reinforcer efficacy. These results show the potential utility of clozapine as a smoking cessation treatment for patients with schizophrenia, in addition to its antipsychotic properties.