Cass W A, Zahniser N R
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Neurosci Lett. 1993 Apr 2;152(1-2):177-80. doi: 10.1016/0304-3940(93)90512-j.
There is general agreement that the brain level of cocaine achieved in response to an intraperitoneal (i.p.) cocaine challenge is higher in animals that have been treated repeatedly with cocaine. However, whether this change in drug disposition persists following withdrawal from repeated treatment is controversial. Rats received either single or repeated injections of cocaine (10 mg/kg, i.p.), and levels of cocaine were measured in dorsal striatum and nucleus accumbens 20 min after the last injection. Cocaine levels were 60-70% higher in both brain regions of rats that had been treated with cocaine once daily for 7 days compared to rats that had received only a single injection. On the 7th day of withdrawal, similar elevations were observed after a challenge injection of cocaine in animals that had been treated repeatedly with cocaine but not in animals that had been treated repeatedly with saline. This persistent pharmacokinetic change should be taken into account in studies of cocaine-induced behavioral sensitization.
人们普遍认为，对腹腔注射（i.p.）可卡因激发产生反应时，经反复给予可卡因治疗的动物大脑中的可卡因水平更高。然而，在反复治疗停药后，这种药物处置的变化是否持续存在存在争议。给大鼠单次或反复注射可卡因（10mg/kg，腹腔注射），并在最后一次注射后20分钟测量背侧纹状体和伏隔核中的可卡因水平。与仅接受单次注射的大鼠相比，每天接受一次可卡因治疗7天的大鼠的两个脑区中的可卡因水平均高出60 - 70%。在停药第7天，经反复给予可卡因治疗的动物在注射可卡因激发后观察到类似的升高，但经反复给予生理盐水治疗的动物则未观察到。在可卡因诱导的行为敏化研究中应考虑这种持续的药代动力学变化。
