Horger B A, Taylor J R, Elsworth J D, Roth R H
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520-8066.
Neuropsychopharmacology. 1994 Nov;11(3):215-22. doi: 10.1038/sj.npp.1380108.
This study examined the role of neurotensin (NT) in the development of cocaine sensitization using the novel nonpeptide NT antagonist SR 48692. Male Sprague-Dawley rats received five daily administrations of SR 48692 (80 micrograms/kg, IP or PO) or vehicle. Following a 7 day drug-free period, cocaine-induced (15 mg/kg, IP) locomotor activity was assessed. Subsequent cocaine tests occurred every other day. No differences were observed between groups during the first day of cocaine testing. Sensitization to the locomotor activating effects of cocaine occurred rapidly in the controls reaching peak effects by the third cocaine challenge injection. By contrast, subjects preexposed to SR 48692 IP were delayed in the development of cocaine sensitization maintaining significantly lower cocaine-induced activity counts relative to controls until the sixth cocaine challenge injection. Preexposure to SR 48692 PO also produced an attenuating effect on the development of cocaine sensitization. The decreased cocaine-induced activity in SR 48692-preexposed subjects did not appear to be the result of a locomotor deficit as SR 48692-preexposed subjects exhibited increased activity rates following a high dose (30 mg/kg, IP) cocaine challenge injection. In an additional experiment, the effect of cotreatment with SR 48692 on the development of cocaine sensitization was assessed. Subjects were cotreated with SR 48692 (80 micrograms/kg, IP) or vehicle 60 minutes prior to each of two cocaine (15 mg/kg, IP) or saline preexposure injections. Following a drug-free day, subjects were tested for cocaine-induced (15 mg/kg, IP) locomotor activation. SR 48692 cotreatment had no effect on the development of sensitization to cocaine.(ABSTRACT TRUNCATED AT 250 WORDS)
本研究使用新型非肽类神经降压素（NT）拮抗剂SR 48692，检测了NT在可卡因致敏作用形成过程中的作用。雄性斯普拉格-道利大鼠每日接受5次SR 48692（80微克/千克，腹腔注射或口服）或赋形剂给药。在7天的无药期后，评估可卡因诱导（15毫克/千克，腹腔注射）的运动活性。随后每隔一天进行一次可卡因测试。在可卡因测试的第一天，各实验组之间未观察到差异。对照组对可卡因的运动激活作用迅速产生致敏，在第三次可卡因激发注射时达到峰值效应。相比之下，预先腹腔注射SR 48692的实验对象在可卡因致敏作用形成过程中出现延迟，相对于对照组，在第六次可卡因激发注射之前，其可卡因诱导的活性计数显著降低。预先口服SR 48692也对可卡因致敏作用的形成产生了减弱效应。预先注射SR 48692的实验对象中可卡因诱导的活性降低，似乎并非运动功能缺陷所致，因为预先注射SR 48692的实验对象在高剂量（30毫克/千克，腹腔注射）可卡因激发注射后，活动率增加。在另一项实验中，评估了与SR 48692联合治疗对可卡因致敏作用形成的影响。在两次可卡因（15毫克/千克，腹腔注射）或生理盐水预先注射前60分钟，给实验对象联合注射SR 48692（80微克/千克，腹腔注射）或赋形剂。在无药一天后，检测实验对象可卡因诱导（15毫克/千克，腹腔注射）的运动激活情况。联合使用SR 48692对可卡因致敏作用的形成没有影响。（摘要截选至250字）
