Costa Fabiana G, Frussa-Filho Roberto, Canteras Newton S, Valera Adriana G, Felicio Luciano F
Departamento de Patologia, Faculdade de Medicina Veterinária e Zootecnia, Universidade de São Paulo, Av. Orlando Marques Paiva 87, Cidade Universitária, 05508-900 São Paulo, SP, Brazil.
Neuropeptides. 2007 Apr;41(2):83-91. doi: 10.1016/j.npep.2006.12.001. Epub 2007 Feb 5.
Psychostimulant-induced locomotor sensitization has been related to changes within the mesolimbic dopamine system and has been suggested to be useful to study mechanisms underlying drug craving. Neurotensin is a neuropeptide co-localized with dopamine in the mesolimbic system. The response to novelty has been suggested to be a predictor of enhanced vulnerability to behavioral sensitization. The effects of repeated treatment with the neurotensin antagonist SR48692 after amphetamine discontinuation were investigated in mice previously classified as high responders (HRs) or low responders (LRs) to novelty. Mice were repeatedly treated with 2.0mg/kg amphetamine, every other day for 11 days. During the first 7 days after amphetamine discontinuation, the animals received a daily injection of saline or 0.3mg/kg SR48692. On the eighth day after amphetamine discontinuation all subjects received a 2.0mg/kg amphetamine challenge injection. Then, mice were tested for an open field behavior and after 90min, were sacrificed for Fos expression quantification in the nucleus accumbens. Both HRs and LRs expressed amphetamine-induced sensitized locomotor activation and increased expression of Fos protein. Treatment with SR48692 prevented behavioral sensitization and Fos protein expression enhancement in LRs but not in HRs mice. These data suggest that neurotensin plays a role in individual variability to amphetamine-induced sensitization.
精神兴奋剂诱导的运动敏化与中脑边缘多巴胺系统内的变化有关，并且被认为有助于研究药物渴望背后的机制。神经降压素是一种与多巴胺共同定位于中脑边缘系统的神经肽。对新奇事物的反应被认为是行为敏化易感性增强的一个预测指标。在先前被分类为对新奇事物高反应者（HRs）或低反应者（LRs）的小鼠中，研究了在停用苯丙胺后重复给予神经降压素拮抗剂SR48692的效果。小鼠每隔一天接受2.0mg/kg苯丙胺重复治疗，共11天。在停用苯丙胺后的前7天，动物每天注射生理盐水或0.3mg/kg SR48692。在停用苯丙胺后的第8天，所有受试者接受2.0mg/kg苯丙胺激发注射。然后，对小鼠进行旷场行为测试，90分钟后，处死小鼠以对伏隔核中的Fos表达进行定量。HRs和LRs均表现出苯丙胺诱导的敏化运动激活以及Fos蛋白表达增加。用SR48692治疗可预防LRs小鼠的行为敏化和Fos蛋白表达增强，但对HRs小鼠无效。这些数据表明神经降压素在苯丙胺诱导的敏化的个体差异中起作用。
