Cashaw J L, Geraghty C A, McLaughlin B R, Davis V E
Neurochemistry and Addiction Research, Veterans Administration Medical Center, Houston, TX 77030.
J Neurosci Res. 1987;18(3):497-503. doi: 10.1002/jnr.490180318.
The effect of ethanol on the concentration of the aberrant dopamine metabolite, tetrahydropapaveroline (THP), in brains of L-dopa-treated rats has been evaluated. THP was isolated from rat brain extract by a newly developed multiple stage separation technique that is highly specific for the alkaloid. THP, dopa, and dopamine were assayed by high-performance liquid chromatography with electrochemical detection. THP was not found in brains of untreated animals. However, levels of 0.42 pmol THP per g brain were observed in animals that received L-dopa (200 mg/kg) by intraperitoneal injection (IP) 90 min before decapitation. Administration of ethanol (3g/kg) IP to L-dopa-treated animals at time intervals ranging from 60 to 240 min before decapitation resulted in significant increases in brain levels of THP as compared to L-dopa-treated animals. Maximum levels of THP (4.02 to 4.82 pmol/g brain) were observed when ethanol was given at time intervals ranging from 80 to 180 min before the animals were killed. Administration of ethanol and L-dopa, as compared to the administration of L-dopa only, markedly increased brain levels of dopa and dopamine. Maximum brain levels of THP, dopa, and dopamine in animals administered ethanol plus L-dopa as compared with L-dopa-treated animals represented a 1048%, 325%, and 84% increase, respectively. These results strongly support the concept that the concentration of THP in the brain of intact animals can be enhanced by ethanol administration.
已评估乙醇对左旋多巴治疗的大鼠脑内异常多巴胺代谢物四氢罂粟碱(THP)浓度的影响。通过一种新开发的对该生物碱具有高度特异性的多级分离技术,从大鼠脑提取物中分离出THP。采用高效液相色谱 - 电化学检测法测定THP、多巴和多巴胺。在未处理动物的脑中未发现THP。然而,在断头前90分钟通过腹腔注射(IP)给予左旋多巴(200mg/kg)的动物中,观察到脑内THP水平为每克脑0.42pmol。在断头前60至240分钟的时间间隔内,对左旋多巴治疗的动物腹腔注射乙醇(3g/kg),与左旋多巴治疗的动物相比,导致脑内THP水平显著升高。当在动物处死前80至180分钟的时间间隔内给予乙醇时,观察到THP的最高水平(4.02至4.82pmol/g脑)。与仅给予左旋多巴相比,给予乙醇和左旋多巴显著提高了脑内多巴和多巴胺的水平。与左旋多巴治疗的动物相比,给予乙醇加左旋多巴的动物脑内THP、多巴和多巴胺的最高水平分别增加了1048%、325%和84%。这些结果有力地支持了乙醇给药可提高完整动物脑内THP浓度这一观点。