EFFECTS OF ANTIPSYCHOTIC-DRUGS ON LATENT INHIBITION - SENSITIVITY AND SPECIFICITY OF AN ANIMAL BEHAVIORAL-MODEL OF CLINICAL DRUG-ACTION
EFFECTS OF ANTIPSYCHOTIC-DRUGS ON LATENT INHIBITION - SENSITIVITY AND SPECIFICITY OF AN ANIMAL BEHAVIORAL-MODEL OF CLINICAL DRUG-ACTION
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DOI：
10.1007/bf02244927
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发表时间：
1993-09-01
影响因子：
3.4
通讯作者：
KILTS, CD
中科院分区：
文献类型：
--
作者：
DUNN, LA;ATWATER, GE;KILTS, CD
条件性情绪反应（CER）的潜在抑制（LI）被认为是选择性注意的一种定量测量。我们已经评估了LI在大鼠中的药理学与精神分裂症的临床药理学的相似之处。将药物和溶剂处理的大鼠分组，并预暴露于笼照明20次作为CS，或不预暴露。所有组均以2个CS-足电击配对进行条件化。第二天CER，作为衡量中断饮酒响应CS介绍，记录。相对于未预暴露的动物，在预暴露动物中观察到LI降低CER。在每天7或14次给药后，氟哌啶醇0.3 mg/kg可增强LI，但单次急性给药后无此作用。氟哌啶醇0.3和0.03 mg/kg剂量增加LI，而0.003和3.0 mg/kg剂量没有影响。氟哌啶醇增强LI不受抗胆碱能药物苯海索联合给药的影响。抗精神病药物氟奋乃静、氯丙嗪、硫噻吨、硫利达嗪、美索达嗪和甲氧氯普胺可增强LI，但氯氮平不增强LI。非抗精神病药物戊巴比妥， 丙咪嗪， 利血平， 苯海索和异丙嗪不能增强LI。 LI与精神分裂症的临床药理学表现出惊人的相似之处。
Latent inhibition (LI) of a conditioned emotional response (CER) has been proposed as a quantitative measure of selective attention. We have assessed the parallels of the pharmacology of LI in rats with the clinical pharmacology of schizophrenia. Drug and vehicle treated rats were divided into groups and preexposed 20 times to cage illumination as a CS, or not preexposed. All groups were conditioned with 2 CS-footshock pairings. The following day CER, as measured by interruption of drinking in response to CS presentation, was recorded. LI was observed as a decreased CER in preexposed relative to non-preexposed animals. LI was enhanced by haloperidol 0.3 mg/kg after 7 or 14 daily treatments, but not after a single acute dose. Haloperidol doses of 0.3 and 0.03 mg/kg enhanced LI, while doses of 0.003 and 3.0 mg/kg had no effect. Haloperidol enhancement of LI was unaffected by the coadministration of the anticholinergic agent trihexyphenidyl. Enhancement of LI is exhibited by the antipsychotic drugs fluphenazine, chlorpromazine, thiothixene, thioridazine, mesoridazine, and metoclopramide but not clozapine. The non-antipsychotic drugs pentobarbital, imipramine, chlordiazepoxide, trihexyphenidyl, and promethazine failed to enhance LI. LI exhibits striking parallels to the clinical pharmacology of schizophrenia.