Whishaw I Q, Mittleman G, Evenden J L
Department of Psychology, University of Lethbridge, Alberta, Canada.
Pharmacol Biochem Behav. 1989 Jan;32(1):211-20. doi: 10.1016/0091-3057(89)90236-0.
Rats were trained on place or cue spatial navigation tasks in a swimming pool and then given the neuroleptic, alpha-flupentixol. Initial experiments showed that regardless of testing schedule, including blocks of trials given concurrently or separated by 7 or 30 days, drugged rats showed a trial-by-trial decay in latency and accuracy of responding although they continued to swim. The rate of decay increased with increases in drug dosage. Further experiments showed that: 1) Performance decay was specifically related to conditioned components of the test environment. Animals required to swim in a different test, or to struggle, showed less decay than rats exposed to the test platform only or required to perform all aspects of the task. 2) Decay was not due to nonspecific effects of neuroleptic treatment because rats injected and replaced in their home cage, and then subsequently reinjected and tested performed like rats treated and tested for the first time. 3) A trial-dependent decay of performance was also obtained in hippocampectomized and decorticate rats, suggesting that at least part of the major action of the drug is on subcortical systems. The results are discussed with respect to hypotheses of neuroleptic action and with respect to their possible relevance to experience-dependent changes in animal analogues of Parkinson's disease. Finally, it is suggested that behavior may be organized in subsystems, which when active, become selectively sensitive to neuroleptics.
将大鼠置于游泳池中进行地点或线索空间导航任务训练，然后给予抗精神病药物α-氟哌噻吨。初步实验表明，无论测试安排如何，包括同时进行的试验组或间隔7天或30天进行的试验组，用药大鼠虽然继续游泳，但反应潜伏期和准确性逐次试验衰退。衰退速率随药物剂量增加而加快。进一步实验表明：1）行为表现衰退与测试环境的条件成分具体相关。需要在不同测试中游泳或挣扎的动物，其衰退程度低于仅暴露于测试平台或需要执行任务所有方面的大鼠。2）衰退并非抗精神病药物治疗的非特异性效应所致，因为注射后放回笼中，随后再次注射并测试的大鼠，其表现与首次治疗和测试的大鼠相似。3）在海马切除和去皮质大鼠中也观察到与试验相关的行为表现衰退，这表明该药物的主要作用至少部分是作用于皮质下系统。结合抗精神病药物作用的假说以及它们与帕金森病动物模型中经验依赖性变化的可能相关性，对这些结果进行了讨论。最后，有人提出行为可能是由子系统组织的，这些子系统在活动时会对抗精神病药物产生选择性敏感。
