Costall B, Naylor R J
Eur J Pharmacol. 1976 Apr;36(2):423-9. doi: 10.1016/0014-2999(76)90096-0.
A comparison was made of the doses of neuroleptic and related agents required to inhibit the stereotyped biting/gnawing/licking response induced in the guinea pig by systemically administered apomorphine and d-amphetamine or by dopamine administered bilaterally into the striatum. Haloperidol. lenperone, fluphenazine (0.5-8 mg/kg i.p.) and fluspirilene (0.125-8 mg/kg i.p.) each inhibited the stereotyped behaviour induced by apomorphine and amphetamine but doses up to 16 mg/kg i.p. failed to modify the dyskinesias induced by intrastriatal dopamine. Pimozide similarly abolished the stereotypies (0.125-8 mg/kg i.p.) but a larger dose (16 mg/kg i.p.) also abolished the dopamine-induced dyskinesias. However, oxiperomide and spiroxatrine were both shown to possess marked anti-dyskinetic (1-2 mg/kg i.p.) as well as anti-stereotypic (0.25-5 mg/kg i.p.) properties. Thioridazine, clothiapine, clozapine, sulpiride and metoclopramide were generally inactive against the stereotypies and dyskinesias although 1.25-5 mg/kg s.c. morphine effectively abolished stereotyped behaviour and the dopamine-induced dyskinesias were inhibited in a small proportion of animals. It is suggested that the dopamine mechanisms involved with stereotypy induction differ from those activated by intrastriatally administered dopamine to induce abnormal oro-facial movements, and that, since only the effects of intrastriatal dopamine showed the same relative degree of resistance to neuroleptic inhibition as clinical dyskinesias, that this may be more applicable to the clinical situation than the stereotypy model.
比较了抑制豚鼠因全身注射阿扑吗啡和d - 苯丙胺或双侧纹状体内注射多巴胺诱导的刻板咬/啃/舔反应所需的抗精神病药物及相关药物剂量。氟哌啶醇、伦哌隆、氟奋乃静(腹腔注射0.5 - 8mg/kg)和氟司必林(腹腔注射0.125 - 8mg/kg)均可抑制阿扑吗啡和苯丙胺诱导的刻板行为,但腹腔注射高达16mg/kg的剂量未能改变纹状体内多巴胺诱导的运动障碍。匹莫齐特同样能消除刻板行为(腹腔注射0.125 - 8mg/kg),但更大剂量(腹腔注射16mg/kg)也能消除多巴胺诱导的运动障碍。然而,奥昔哌隆和螺沙群均显示出显著的抗运动障碍特性(腹腔注射1 - 2mg/kg)以及抗刻板行为特性(腹腔注射0.25 - 5mg/kg)。硫利达嗪、氯噻平、氯氮平、舒必利和甲氧氯普胺通常对刻板行为和运动障碍无活性,尽管皮下注射1.25 - 5mg/kg吗啡能有效消除刻板行为,且一小部分动物的多巴胺诱导的运动障碍受到抑制。提示与刻板行为诱导相关的多巴胺机制不同于纹状体内注射多巴胺激活以诱导异常口面部运动的机制,并且,由于只有纹状体内多巴胺的作用表现出与临床运动障碍相同相对程度的抗精神病药物抑制抗性,因此这可能比刻板行为模型更适用于临床情况。