Kuruvilla A, Fung Y K, Uretsky N J
Neuropharmacology. 1982 Sep;21(9):891-7. doi: 10.1016/0028-3908(82)90081-8.
This study was designed to determine the behavioral and biochemical effects of the gamma-aminobutyric acid (GABA) agonist, muscimol, in mice withdrawn from chronic haloperidol administration. Mice received either haloperidol or vehicle In their drinking water for 35 days, after which the haloperidol was replaced with vehicle. Seven days after withdrawal from chronic treatment with haloperidol, the effect of apomorphine on the climbing behavior of haloperidol-withdrawn mice was markedly enhanced as compared to control mice that received only vehicle. Muscimol produced a dose-related reduction in the intensity of climbing behavior induced by apomorphine in both control and haloperidol-withdrawn mice. However, the inhibition of climbing behavior induced by muscimol was significantly greater in haloperidol-withdrawn animals. In addition, in haloperidol-withdrawn mice, muscimol produced a significant reduction in striatal homovanillic (HVA) levels with no change in striatal dopamine (DA) levels, suggesting a decrease in DA turnover. In support of this conclusion, muscimol decreased the disappearance of dopamine in haloperidol-withdrawn mice that were injected with alpha-methyl-p-tyrosine. Both the behavioral and biochemical effects of muscimol were blocked by the GABA antagonist, picrotoxin. These results indicate that after chronic haloperidol administration there is not only an enhanced response to dopaminergic agonists but also to GABAergic agonists.
本研究旨在确定γ-氨基丁酸（GABA）激动剂蝇蕈醇对长期给予氟哌啶醇后停药小鼠的行为和生化影响。小鼠在饮用水中接受氟哌啶醇或赋形剂处理35天，之后用赋形剂替代氟哌啶醇。在从氟哌啶醇的长期治疗中停药7天后，与仅接受赋形剂的对照小鼠相比，阿扑吗啡对氟哌啶醇停药小鼠攀爬行为的影响明显增强。蝇蕈醇在对照小鼠和氟哌啶醇停药小鼠中均产生了与剂量相关的阿扑吗啡诱导的攀爬行为强度降低。然而，蝇蕈醇对攀爬行为的抑制在氟哌啶醇停药动物中明显更大。此外，在氟哌啶醇停药小鼠中，蝇蕈醇使纹状体高香草酸（HVA）水平显著降低，而纹状体多巴胺（DA）水平无变化，提示DA周转率降低。为支持这一结论，蝇蕈醇减少了注射α-甲基-对-酪氨酸的氟哌啶醇停药小鼠中多巴胺的消失。蝇蕈醇的行为和生化作用均被GABA拮抗剂印防己毒素阻断。这些结果表明，长期给予氟哌啶醇后，不仅对多巴胺能激动剂的反应增强，而且对GABA能激动剂的反应也增强。
