Gunne L M, Growdon J, Glaeser B
Psychopharmacology (Berl). 1982;77(2):134-9. doi: 10.1007/BF00431935.
After 10-12 weeks of chronic haloperidol administration rats with frontal cortex ablations or lesions induced by intracerebroventricular infection of 6-hydroxydopamine developed vacuous chewing behavior at a fairly stable frequency (bifrontal ablations had 15-20, 6-hydroxy-dopamine lesioned rats 7-12 chewing movements/min). This behavior persisted for 10 weeks after the last injection of haloperidol decanoate. However, rats with frontal cortex lesions developed a low rate of vacuous chewings (4-8 chewings/min) even without haloperidol administration. Bilateral intrastriatal injections of kainic acid in combination with chronic haloperidol administration did not cause chewing movements in excess of unlesioned haloperidol-treated controls. Pharmacological tests of this animal model for tardive dyskinesia (TD) revealed similarities to human TD, but also differences. Dopamine agonists (apomorphine) and antagonists (haloperidol) both lowered chewing behavior analogous to reported effects on TD and so did gabaculine. The cholinergic drugs physostigmine and pilocarpine, however, increased chewing in rats, while anticholinergics (atropine) reduced it, in contrast to reported effects on human TD.
在给予慢性氟哌啶醇10 - 12周后，接受额叶皮质切除或经脑室内注射6 - 羟基多巴胺诱导损伤的大鼠，会以相当稳定的频率出现空嚼行为（双侧额叶切除的大鼠每分钟有15 - 20次，6 - 羟基多巴胺损伤的大鼠每分钟有7 - 12次咀嚼动作）。这种行为在最后一次注射癸酸氟哌啶醇后持续了10周。然而，即使不给予氟哌啶醇，额叶皮质损伤的大鼠空嚼频率也较低（每分钟4 - 8次）。双侧纹状体内注射 kainic 酸并联合慢性给予氟哌啶醇，并未导致咀嚼动作超过未损伤的氟哌啶醇处理对照组。对这种迟发性运动障碍（TD）动物模型的药理学测试显示，它与人类TD既有相似之处，也有不同之处。多巴胺激动剂（阿扑吗啡）和拮抗剂（氟哌啶醇）都降低了咀嚼行为，类似于对TD的报道效应，加巴喷丁也是如此。然而，胆碱能药物毒扁豆碱和毛果芸香碱增加了大鼠的咀嚼行为，而抗胆碱能药物（阿托品）则减少了咀嚼行为，这与对人类TD的报道效应相反。
