Voith K
Psychopharmacology (Berl). 1985;85(4):405-9. doi: 10.1007/BF00429654.
The effect of the chemically novel dopaminergic agonist, ciladopa (AY-27,110) was studied on rotational behavior in unilaterally 6-OHDA-lesioned rats and on stereotyped behavior in normal animals during and after chronic treatment. Ciladopa, at a 1.25 mg/kg SC daily dose, was administered for 4 and 6 weeks to the lesioned and normal animals, respectively. This dose was threshold for turning but subthreshold with respect to stereotypy. Both behaviors were evaluated weekly during chronic treatment and biweekly for 11 weeks after its discontinuation in response to doses previously shown to elicit turning and stereotypy. The chronic administration of ciladopa enhanced rotational behavior considerably more and with an earlier onset than stereotypy, although the duration of behavioral supersensitivity after cessation of treatment was the same. These results indicate that behaviors mediated by supersensitive or intact dopamine receptors are differently affected by chronic dopamine agonist treatment. The results are discussed in relation to their potential therapeutic implications and current concepts of agonist-induced supersensitivity.
研究了化学结构新颖的多巴胺能激动剂西拉多巴(AY - 27,110)对单侧6 - 羟基多巴胺损伤大鼠旋转行为以及对正常动物慢性给药期间和之后刻板行为的影响。分别以1.25mg/kg的皮下日剂量对损伤动物和正常动物给药4周和6周。该剂量对旋转行为来说是阈剂量,但对刻板行为来说是阈下剂量。在慢性给药期间每周评估这两种行为,在停药后每两周评估11周,以响应先前显示能引发旋转和刻板行为的剂量。尽管停药后行为超敏反应的持续时间相同,但西拉多巴的慢性给药对旋转行为的增强作用比刻板行为大得多,且起效更早。这些结果表明,由超敏或完整多巴胺受体介导的行为受慢性多巴胺激动剂治疗的影响不同。结合其潜在治疗意义和激动剂诱导超敏反应的当前概念对结果进行了讨论。