苯丙胺诱发小鼠激怒反应及其机制

AMPHETAMINE-INDUCED RAGE REACTION IN MICE AND ITS MECHANISM

苯丙胺15mg/kg ip能诱发小鼠激怒反应,使小鼠出现攻击和殴斗行为。强安定药、弱安定药和利血平有明显拮抗效果。镇静剂如巴比妥类、抗胆碱药及抗肾上腺素药均无拮抗作用。金刚胺、左旋多巴和阿扑吗啡均能增强苯丙胺的激怒效应。因苯丙胺激怒小鼠的方法简便易行,可作为筛选抗精神病药的动物模型。苯丙胺产生激怒作用的机制与增强多巴胺能神经的功能有关,推测可能是促进边缘系统多巴胺释放的结果。

Rage reaction was induced in mice by ip amphetamine sulfate (APT) 15 mg/kg.Mice appeared hyperreactive after 6 min and then squeaked and fought each other. These manifesta-tions were most distinct in 15～30 min and subsided after 40～70 min. At 20°C and 25°C, the occur-fence of rage reaction was 85. 0% and 90. 0% respectively. The ED_(50) of APT for eliciting rage reac-tion was 11.8±2.1 mg/kg ip. No significant difference in the induction of rage reaction was ob-served between ? and ? mice but ambient temperature affected the occurrence of this reaction.Neuroleptic drugs (chlorpromazine, haloperidol, tardan and clozapine), anxiolytic drugs (diazepamand meprobamate) and reserpine suppressed the rage reaction induced by APT in mice. Phenobarbitaland pentobarbital (at sedative doses), atropine, scopolamine, phentolamine and propranolol exertedno influence on APT-induced rage reaction. Amantadine, levodopa and apomorphine at lower dosespotentiated the rage inducing effect of APT. Moreover, at higher doses amantadine or levodopa alonealso evoked rage reaction similar to that induced by APT. Therefore, it may be deduced that the APT-induced rage reaction results from increased release of dopamine in limbic system and has nothing todo with the simultaneous epinephrine release. The available data indicate that the APT-induced ragereaction in mice deserves to be recommended as an animal model for screenin g potential neuroleptic dru-gs. The merits and shortcomings of this new model are discussed.