氯氮平、氟哌啶醇和氟西汀对可卡因诱导的运动敏化逆转的影响。
Effects of clozapine, haloperidol, and fluoxetine on the reversal of cocaine-induced locomotor sensitization.
机构信息
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea. ; Institute of Human Behavioral Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
出版信息
Psychiatry Investig. 2014 Oct;11(4):454-8. doi: 10.4306/pi.2014.11.4.454. Epub 2014 Oct 20.
OBJECTIVE
Repeated treatment with psychostimulants induces sensitization of the dopaminergic system in the brain. Dopaminergic sensitization has been proposed as a mechanism of psychosis. Although antipsychotics block the expression of sensitized behavior, they are ineffective for reversing the sensitized state. We investigated the effect of clozapine, haloperidol, and fluoxetine on the reversal of cocaine-induced behavioral sensitization.
METHODS
Male ICR mice were sensitized to cocaine with repeated treatment. Animals were then split into four groups, and each group was treated with vehicle or one of the above drugs for 5 days. After a 3-day drug washout, locomotor activity was assessed before and after a cocaine challenge.
RESULTS
Clozapine reversed the sensitized state, whereas haloperidol did not. Fluoxetine seemed to reverse the sensitization partially.
CONCLUSION
We confirmed that D2 blockade was not effective for reversing sensitization. The reversal by clozapine is partially explained in terms of its strong 5-HT2 and weak D2 affinity. The partial reversal by fluoxetine seemed to be related to its serotonin-augmenting action.
目的
反复使用精神兴奋剂会导致大脑中多巴胺能系统的敏化。多巴胺能敏化被认为是精神病的一种机制。虽然抗精神病药可以阻断敏化行为的表达，但它们对于逆转敏化状态无效。我们研究了氯氮平、氟哌啶醇和氟西汀对可卡因诱导的行为敏化逆转的影响。
方法
雄性 ICR 小鼠通过重复处理对可卡因产生敏化。然后，将动物分为四组，每组用载体或上述药物之一处理 5 天。在 3 天的药物洗脱后，在可卡因挑战前后评估运动活动。
结果
氯氮平逆转了敏化状态，而氟哌啶醇则没有。氟西汀似乎部分逆转了敏化。
结论
我们证实 D2 阻断对于逆转敏化无效。氯氮平的逆转部分可以用其对 5-HT2 的强烈亲和力和对 D2 的弱亲和力来解释。氟西汀的部分逆转似乎与它增强血清素的作用有关。
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