BioMedical Research, Wageningen University and Research Center, Lelystad, The Netherlands.
Psychopharmacology (Berl). 2009 Nov;206(4):715-29. doi: 10.1007/s00213-009-1599-z. Epub 2009 Jul 23.
Rodents are usually used to assess the ability of antipsychotic drugs to antagonize hyperlocomotion induced by dopamine agonists, such as the psychostimulant d-amphetamine. However, the substantial differences between rodents and humans may hinder extrapolation of experimental results to humans. For this reason, we speculated that Göttingen miniature pigs, which show strong physiological and genetic homology with humans, might be a better model for investigating the effects of antipsychotics. To investigate this, we determined whether d-amphetamine induced hyperlocomotion in miniature pigs and whether this effect was reversible by antipsychotics.
d-amphetamine was tested in the dose range of 0.2 to 2.0 mg kg(-1) for its ability to induce hyperactivity in the open field, and the effects of two antipsychotics, haloperidol and risperidone, on amphetamine-induced hyperactivity were examined.
d-amphetamine increased open-field activity at 0.2, 0.4, and 0.7 mg kg(-1) s.c. but not at higher doses. The stimulation of open-field activity induced by 0.4 mg kg(-1) s.c. d-amphetamine was antagonized by haloperidol and risperidone (0.01 and 0.04 mg kg(-1) s.c.).
d-amphetamine-induced hyperlocomotion in miniature pigs may be a useful model for studying the effect of putative antipsychotics.
通常使用啮齿动物来评估抗精神病药物拮抗多巴胺激动剂（如精神兴奋剂 d-苯丙胺）诱导的过度活动的能力。然而，啮齿动物和人类之间的巨大差异可能会阻碍将实验结果推断到人类身上。出于这个原因，我们推测具有与人类很强的生理和遗传同源性的哥廷根小型猪可能是研究抗精神病药作用的更好模型。为了研究这一点，我们确定了 d-苯丙胺是否会引起小型猪的过度活动，以及抗精神病药是否可以逆转这种作用。
测试了 d-苯丙胺在 0.2 至 2.0 mg kg(-1) 剂量范围内诱导其在开放场中的过度活动的能力，并且检查了两种抗精神病药，氟哌啶醇和利培酮，对安非他命诱导的过度活动的影响。
d-苯丙胺在 0.2、0.4 和 0.7 mg kg(-1) 皮下注射时增加了开放场活动，但在更高剂量时没有增加。皮下注射 0.4 mg kg(-1) 的 d-苯丙胺引起的开放场活动刺激被氟哌啶醇和利培酮（0.01 和 0.04 mg kg(-1) 皮下注射）拮抗。
d-苯丙胺诱导的小型猪过度活动可能是研究假定抗精神病药作用的有用模型。
