The effects of kainic acid lesions on locomotor responses to haloperidol and clozapine
The effects of kainic acid lesions on locomotor responses to haloperidol and clozapine
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DOI：
10.1007/s002130050509
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发表时间：
1998-02-01
影响因子：
3.4
通讯作者：
Csernansky, JG
中科院分区：
文献类型：
--
作者：
Bardgett, ME;Jackson, JL;Csernansky, JG
大多数临床有效的抗精神病药物可降低大鼠自发和安非他明引起的自发活动。我们最近已经证明，脑室内输注海人酸（KA），在海马和其他边缘皮质脑区产生细胞损失，增加自发和安非他明引起的运动。本研究确定KA病变是否改变抗精神病药物氟哌啶醇和氯氮平对自发和苯丙胺引起的运动行为的抑制作用。年轻的成年雄性大鼠（70日龄）接受脑室注射的车辆或KA，这产生海马锥体细胞损失，在每只大鼠和更多的变量细胞损失或胶质细胞增生的杏仁核，梨状皮质？和背侧丘脑。手术后30天，每周一次测试损伤大鼠和对照大鼠对药物治疗的运动反应。如前所述，受损动物的自发活动和安非他明（1.50 mg/kg SC）引起的活动过度大于对照动物。此外，氟哌啶醇给药（0.13、0.35或1.50 mg/kg SC）后，在病变大鼠中观察到的自发活动和/或苯丙胺引起的过度运动水平高于对照组。运动反应低（6.30毫克/公斤）和中等剂量的氯氮平（20毫克/公斤）是相似的病变和对照组大鼠？尽管在给予高剂量的氯氮平（30 mg/kg）后，损伤大鼠比对照组更活跃。这些数据表明，与边缘皮质病变相关的多动可能对氟哌啶醇逆转不敏感，但对氯氮平抑制特别敏感。
Spontaneous and amphetamine-elicited locomotor activity in rats is reduced by most clinically effective antipsychotic drugs. We have recently demonstrated that intracerebroventricular infusion of kainic acid (KA), which produces cell loss in the hippocampus and other limbic-cortical brain regions, increases spontaneous and amphetamine-elicited locomotion. The present study determined if KA lesions alter the suppressive effects of the antipsychotic drugs, haloperidol and clozapine, on spontaneous and amphetamine-elicited locomotor behavior. Young adult male rats (70 days of age) received intracerebroventricular infusions of vehicle or KA, which produced hippocampal pyramidal cell loss in each rat and more variable cell loss or gliosis in the amygdala, piriform cortex? and laterodorsal thalamus. Thirty days post-surgery, lesioned and control rats were tested once a week for locomotor responses to drug treatments. As observed previously, spontaneous locomotor activity and hyperactivity elicited by amphetamine (1.50 mg/kg SC) were greater in lesioned animals than controls. In addition, the level of spontaneous activity and/or amphetamine-elicited hyperlocomotion observed in lesioned rats after haloperidol treatment (0.13, 0.35, or 1.50 mg/kg SC) was greater than that found in controls. Locomotor responses to low (6.30 mg/kg) and moderate doses of clozapine (20 mg/kg) were similar in lesioned and control rats? although lesioned rats were more active than controls following the administration of a high dose of clozapine (30 mg/kg). These data indicate that the hyperactivity associated with limbic-cortical lesions may be insensitive to reversal by haloperidol, yet uniquely sensitive to suppression by clozapine.