Tieppo C A, Ferreira F S, Sassatani A S, Felicio L F, Nasello A G
Departamento de Ciências Fisiológicas, Faculdade de Ciências Médicas da Santa Casa de SP, R. Dr. Cesário Motta Jr, 61, 11 andar, São Paulo, Brazil.
Eur J Pharmacol. 2000 Jan 10;387(2):189-96. doi: 10.1016/s0014-2999(99)00782-7.
Stereotyped behavior is elicited by activation of dopaminergic systems with drugs such as apomorphine and amphetamine. In previous studies, we have reported that the sulfated cholecystokinin octapeptide (CCK-8) decreased apomorphine-induced stereotypy in animals with normal and supersensitive dopamine receptors. The aim of the present study was to evaluate the effects of CCK(1) and CCK(2) receptor antagonists on stereotyped behavior induced by apomorphine or amphetamine. Rats were pretreated with the CCK(1) (SR 27897B; 1-[[2-(4-(2-chlorophenyl) thiazol-2-yl) aminocarbonyl]indolyl]acetic acid; 500 microg/kg; i.p.) or CCK(2) (L-365,260; 3R-(+)-N-(2,3-dihydro-1-methyl-2-oxo-5 phenyl-1H-1, 4-benzodiazepine-3-yl)-N'-(3-methyl phenyl)-urea; 500 microg/kg; i.p. ) receptor antagonists or saline 15 min before apomorphine (0.6 mg/kg; s.c.) or amphetamine (9.0 mg/kg; i.p.) injection. Both CCK(1) and CCK(2) receptor antagonists significantly increased apomorphine-induced stereotypy. In contrast, only the blockade of CCK(2) receptors significantly decreased amphetamine-induced stereotypy. The results suggest a dual opposite mechanism for CCK-dopamine interactions. These data also suggest that both apomorphine- and amphetamine-induced stereotypy should be used whenever effects of drugs acting on dopaminergic systems are being assessed.
刻板行为可由阿扑吗啡和苯丙胺等药物激活多巴胺能系统引发。在先前的研究中，我们报道过硫酸化胆囊收缩素八肽（CCK-8）可减少正常和多巴胺受体超敏动物中阿扑吗啡诱导的刻板行为。本研究的目的是评估CCK(1)和CCK(2)受体拮抗剂对阿扑吗啡或苯丙胺诱导的刻板行为的影响。给大鼠腹腔注射CCK(1)受体拮抗剂（SR 27897B；1-[[2-(4-(2-氯苯基)噻唑-2-基)氨基羰基]吲哚基]乙酸；500微克/千克）或CCK(2)受体拮抗剂（L-365,260；3R-(+)-N-(2,3-二氢-1-甲基-2-氧代-5-苯基-1H-苯并二氮杂卓-3-基)-N'-(3-甲基苯基)-脲；500微克/千克）或生理盐水，15分钟后皮下注射阿扑吗啡（0.6毫克/千克）或腹腔注射苯丙胺（9.0毫克/千克）。CCK(1)和CCK(2)受体拮抗剂均显著增加了阿扑吗啡诱导的刻板行为。相比之下，只有阻断CCK(2)受体显著减少了苯丙胺诱导的刻板行为。结果提示CCK与多巴胺相互作用存在双重相反机制。这些数据还表明，在评估作用于多巴胺能系统的药物效果时，应同时使用阿扑吗啡和苯丙胺诱导的刻板行为。
