Nicotine and clozapine effects on attentional performance impaired by the NMDA antagonist dizocilpine in female rats.
Nicotine and clozapine effects on attentional performance impaired by the NMDA antagonist dizocilpine in female rats.
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DOI：
10.1017/s1461145706007528
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发表时间：
2008-02
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影响因子：
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通讯作者：
A. Rezvani;Ehsan Kholdebarin;E. Dawson;E. Levin
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文献类型：
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作者：
A. Rezvani;Ehsan Kholdebarin;E. Dawson;E. Levin
认知障碍在精神分裂症中非常普遍，目前在大多数患者中治疗不足。注意力缺陷是精神分裂症的标志性症状之一。抗精神病药物，这可能是非常有效的打击幻觉往往是无效的，在减少认知障碍，并可能加强认知障碍。以前，我们发现，抗精神病药物氯氮平损害，而尼古丁改善，在正常大鼠进行视觉信号检测注意力任务的大鼠的准确性。对于目前的研究，在精神分裂症的认知障碍与NMDA拮抗剂地佐环平（0.05毫克/公斤）的模型，我们研究了氯氮平和尼古丁对显着受损的注意命中准确性的影响。氯氮平（1.25 mg/kg）或尼古丁（0.025 mg/kg）可显著（p<0.05）逆转地佐环平引起的损伤。有趣的是，当氯氮平和尼古丁一起服用时，它们会阻止彼此的有益作用。当有效剂量为1.25 mg/kg的氯氮平和0.025 mg/kg的尼古丁同时给予时，该组合不再显著逆转地佐环平诱导的命中准确性损害。鉴于绝大多数精神分裂症患者吸烟，氯氮平对注意力功能的潜在有益作用可能在很大程度上被自我给药的尼古丁阻断。此外，有关于尼古丁治疗逆转认知缺陷，包括注意力障碍的发展有希望的结果。这在目前的研究中得到了尼古丁逆转地佐环平诱导的注意力障碍的支持。然而，在精神分裂症中，尼古丁治疗的疗效可能会受到与抗精神病药物（如氯氮平）联合治疗的限制。这将是重要的，以确定哪些复杂的影响氯氮平和尼古丁是逆转注意力障碍的关键，以及他们如何阻止对方的影响治疗精神分裂症的注意力障碍的发展。
Cognitive impairment is very prevalent in schizophrenia and is currently undertreated in most patients. Attentional deficit is one of the hallmark symptoms of schizophrenia. Antipsychotic drugs, which can be quite effective in combating hallucinations are often ineffective in reducing cognitive impairment and can potentiate cognitive impairment. Previously, we found that the antipsychotic drug clozapine impaired, while nicotine improved, the accuracy of rats performing a visual signal detection attentional task in normal rats. For the current study, in a model of cognitive impairment of schizophrenia with the NMDA antagonist dizocilpine (0.05 mg/kg), we examined the effects of clozapine and nicotine on significantly impaired attentional hit accuracy. This dizocilpine-induced impairment was significantly (p<0.05) reversed by either clozapine (1.25 mg/kg) or nicotine (0.025 mg/kg). Interestingly, when clozapine and nicotine were given together, they blocked each other's beneficial effects. When the effective doses of 1.25 mg/kg clozapine and 0.025 mg/kg nicotine were given together the combination no longer significantly reversed the dizocilpine-induced hit-accuracy impairment. Given that the great majority of people with schizophrenia smoke, the potential beneficial effects of clozapine on attentional function may be largely blocked by self-administered nicotine. In addition, there are promising results concerning the development of nicotinic treatments to reverse cognitive deficits including attentional impairment. This is supported in the current study by the reversal of the dizocilpine-induced attentional impairment by nicotine. However, in schizophrenia the efficacy of nicotinic treatments may be limited by co-treatment with antipsychotic drugs like clozapine. It will be important to determine which of the complex effects of clozapine and nicotine are key in reversing attentional impairment and how they block each other's effects for the development of therapy to combat the attentional impairment of schizophrenia.