Spangler R, Zhou Y, Maggos C E, Zlobin A, Ho A, Kreek M J
Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, NY 10021, USA.
Neuroreport. 1996 Sep 2;7(13):2196-200. doi: 10.1097/00001756-199609020-00028.
The modulation by selective dopamine receptor antagonists of the effects of "binge' cocaine (3 x 15 mg kg-1 day-1, i.p., for 3 days after 11 days of adaptation to saline injections) on preproenkephalin, preprodynorphin, kappa opioid receptor and dopamine transporter mRNAs was determined. Administration of cocaine was preceded by daily single injections of a D1 (SCH 23390; 2 mg kg-1) or the D2 (sulpiride; 50 mg kg-1) dopamine receptor antagonist. The D1, and not the D2, antagonist blocked cocaine-induced preprodynorphine and preproenkephalin increases in the caudate-putamen. Sulpiride alone, and sulpiride plus cocaine, increased preproenkephalin mRNA. Dopamine transporter mRNA levels showed a cocaine treatment-antagonist interaction. These data indicate that this administration paradigm elevates both preprodynorphin and preproenkephalin mRNAs by a D1-dependent mechanism not requiring D2 activation.
研究了选择性多巴胺受体拮抗剂对“暴饮暴食”剂量可卡因（适应盐水注射11天后，每天腹腔注射3次，每次15 mg/kg，连续3天）对前脑啡肽原、前强啡肽原、κ阿片受体和多巴胺转运体mRNA影响的调节作用。在给予可卡因之前，每天单次注射D1多巴胺受体拮抗剂（SCH 23390；2 mg/kg）或D2多巴胺受体拮抗剂（舒必利；50 mg/kg）。D1而非D2拮抗剂可阻断可卡因诱导的尾状核-壳核中前强啡肽原和前脑啡肽原的增加。单独使用舒必利以及舒必利加可卡因均可增加前脑啡肽原mRNA。多巴胺转运体mRNA水平显示出可卡因治疗与拮抗剂之间的相互作用。这些数据表明，这种给药模式通过不依赖D2激活的D1依赖性机制提高了前强啡肽原和前脑啡肽原mRNA水平。
