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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Does MK-801 discrimination constitute an animal model of schizophrenia useful for detecting atypical antipsychotics?
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Does MK-801 discrimination constitute an animal model of schizophrenia useful for detecting atypical antipsychotics?

机译：MK-801歧视是否构成可用于检测非典型抗精神病药的精神分裂症动物模型？

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Two groups of female Wistar rats were trained to discriminate two doses (0.075 and 0.0375 mg/kg) of the noncompetitive NMDA antagonist MK-801 (dizocilpine) in a food-rewarded operant FR30 drug discrimination task. The atypical neuroleptic clozapine (2-6 mg/kg) produced only minimal antagonism (max. 32%) of the MK-801 cue at either training dose, and the "antagonist" effects were not clearly dose related. Furthermore, in the 0.075 mg/kg trained animals clozapine at 3 mg/kg failed to shift the MK-801 dose-response curve to the right. The alpha1-adrenoceptor antagonist prazosin (1-8 mg/kg) was also tested for antagonism of the 0.0375 mg/kg MK-801 cue, and again, only partial antagonism was seen (maximum 36%). Recently, it was suggested [4] that as the discriminative stimulus produced by MK-801 (0.075 mg/kg) was fully antagonized by clozapine at 3 mg/kg, but not by the typical neuroleptic haloperidol, this assay may be a useful screen for detecting atypical neuroleptics. It would seem, however, that this is not necessarily the case, and that the MK-801 discriminative cue may not be psychotomimetic. However, as this was a food rewarded rather than an avoidance paradigm that was used in the prior study [4], it may be that the drug discrimination procedure itself is a critical factor, although this hypothesis requires empirical testing.
机译：训练了两组雌性Wistar大鼠，以区分两种剂量（0.075和0.0375 mg / kg）的非竞争性NMDA拮抗剂MK-801（地佐西平）进行食物奖励操作性FR30药物区分任务。非典型的精神抑制药氯氮平（2-6 mg / kg）在两种训练剂量下仅产生最小的拮抗作用（最大32％），并且“拮抗剂”作用与剂量没有明显关系。此外，在0.075 mg / kg受过训练的动物中，氯氮平3 mg / kg不能使MK-801剂量反应曲线向右移动。还测试了α1-肾上腺素能受体拮抗剂哌唑嗪（1-8 mg / kg）对0.0375 mg / kg MK-801信号的拮抗作用，再次可见仅部分拮抗作用（最大36％）。最近，有人建议[4]，因为氯氮平以3 mg / kg完全拮抗MK-801（0.075 mg / kg）产生的歧视性刺激，但典型的抗精神病药物氟哌啶醇却没有拮抗作用，因此该测定可能是有用的筛选方法用于检测非典型的抗精神病药。但是，似乎不一定是这种情况，并且MK-801判别提示可能不是拟精神病药物。但是，由于这是对食物的奖励，而不是先前研究中使用的回避范式[4]，因此尽管该假设需要经验检验，但药物歧视程序本身可能是一个关键因素。

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