COCAINE AND COCAETHYLENE - MICRODIALYSIS COMPARISON OF BRAIN DRUG LEVELS AND EFFECTS ON DOPAMINE AND SEROTONIN
COCAINE AND COCAETHYLENE - MICRODIALYSIS COMPARISON OF BRAIN DRUG LEVELS AND EFFECTS ON DOPAMINE AND SEROTONIN
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DOI：
10.1111/j.1471-4159.1993.tb03305.x
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发表时间：
1993-04-01
影响因子：
4.7
通讯作者：
ROTH, RH
中科院分区：
文献类型：
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作者：
BRADBERRY, CW;NOBILETTI, JB;ROTH, RH
可卡乙烯是一种具有药理活性的代谢物，由同时消耗可卡因和乙醇产生。可卡因和可卡乙烯对伏隔核中多巴胺和纹状体中血清素细胞外水平的影响在麻醉大鼠体内进行了表征。使用静脉内(3μmol/kg)和腹膜内(44μmol/kg)给药途径。除了监测神经递质水平外，静脉内给药后每隔 4 分钟测定一次可卡因和可卡乙烯的微透析液水平，腹膜内给药后每隔 20 分钟测定一次可卡因和可卡乙烯的微透析液水平。当静脉内给予可卡因和可卡乙烯时，伏隔核中的细胞外多巴胺水平增加至注射前值的约400%。可卡因使纹状体血清素显着增加至注射前值的 200%，而可卡乙烯则没有效果。静脉注射后可卡因和可卡乙烯的脑水平没有差异。腹腔注射后，伏隔核细胞外多巴胺水平可卡因增加至注射前水平的400%，但可卡乙烯仅增加至注射前水平的200%，差异具有统计学意义。可卡因使血清素水平增加至注射前水平的 360%，但可卡乙烯仅增加至注射前水平的 175%。大脑中达到的可卡因水平显着高于可卡乙烯，表明与腹膜内途径的药代动力学差异。这些结果在体内证实，在多巴胺和血清素摄取方面，可卡乙烯的作用比可卡因更具选择性。此外，还观察到脑药物水平的途径依赖性差异可能会影响对这些化合物的强化值的相对效力的解释。
Cocaethylene is a pharmacologically active metabolite resulting from concurrent cocaine and ethanol consumption. The effects of cocaine and cocaethylene on extracellular levels of dopamine in the nucleus accumbens, and serotonin in the striatum were characterized in vivo in the anesthetized rat. Both intravenous (3 mumol/kg) and intraperitoneal (44 mumol/kg) routes of administration were used. In addition to monitoring neurotransmitter levels, microdialysate levels of cocaine and cocaethylene were determined at 4-min intervals after intravenous administration, and at 20-min intervals after intraperitoneal administration. Extracellular levels of dopamine in the nucleus accumbens were increased to approximately 400% of preinjection value by both cocaine and cocaethylene when administered intravenously. Cocaine caused a significant increase of striatal serotonin to 200% preinjection value, whereas cocaethylene had no effect. Brain levels of cocaine and cocaethylene after intravenous administration did not differ. After intraperitoneal administration, extracellular levels of dopamine in the nucleus accumbens were increased to 400% of preinjection levels by cocaine, but were only increased to 200% of preinjection levels by cocaethylene, the difference being statistically significant. Serotonin levels were increased to 360% of preinjection levels by cocaine, but only to 175% of preinjection value by cocaethylene. Levels of cocaine attained in brain were significantly higher than those for cocaethylene, suggesting pharmacokinetic differences with the intraperitoneal route. These results confirm in vivo that cocaethylene is more selective in its actions than cocaine with respect to dopamine and serotonin uptake. In addition, route-dependent differences in attainment of brain drug levels have been observed that may impact on interpretations of the relative potency of the reinforcement value of these compounds.