Coward D M
Psychopharmacology (Berl). 1982;78(2):180-4. doi: 10.1007/BF00432259.
The present study compared the ability of neuroleptic and non-neuroleptic agents to modify the sensitivity of nigral, GABA-sensitive, non-dopaminergic efferents in the rat after sub-chronic administration. Pre-treatment with haloperidol or clebopride, 1.0 mg/kg PO for 10 days, induced supersensitivity to the behavioural effects of unilateral intranigral muscimol, 5.0 ng, on withdrawal day 1. This effect was no longer significant in other rats tested on withdrawal day 7. In contrast, similar pre-treatment with sulpiride, 20 mg/kg PO, led to significantly enhanced responses to intra-nigral muscimol on both withdrawal days. Pre-treatment with clozapine, 20 mg/kg, or thioridazine, 12 mg/kg PO, did not lead to supersensitivity on withdrawal day 1, but did so on withdrawal day 7. Pre-treatment with amitriptyline, 20 mg/kg PO, or metoclopramide, 1.0 mg/kg PO, failed to result in supersensitivity on either withdrawal day. The data confirm previous biochemical and behavioural findings suggesting that repeated administration of neuroleptics can induce nigral GABA-ergic supersensitivity in the rat, but demonstrate that this action is not an exclusive property of classical, cataleptogenic agents.
本研究比较了抗精神病药物和非抗精神病药物在亚慢性给药后改变大鼠黑质、GABA敏感、非多巴胺能传出神经敏感性的能力。用氟哌啶醇或氯波必利预处理，1.0mg/kg口服，持续10天，在撤药第1天对单侧黑质内注射5.0ng蝇蕈醇的行为效应诱导超敏反应。在撤药第7天测试的其他大鼠中，这种效应不再显著。相比之下，用舒必利20mg/kg口服进行类似预处理，在两个撤药日对黑质内注射蝇蕈醇的反应均显著增强。用氯氮平20mg/kg或硫利达嗪12mg/kg口服预处理，在撤药第1天未导致超敏反应，但在撤药第7天导致超敏反应。用阿米替林20mg/kg口服或甲氧氯普胺1.0mg/kg口服预处理，在两个撤药日均未导致超敏反应。这些数据证实了先前的生化和行为学研究结果，表明反复给予抗精神病药物可在大鼠中诱导黑质GABA能超敏反应，但表明这种作用并非经典致僵剂的独有特性。
