Spangler R, Zhou Y, Schlussman S D, Ho A, Kreek M J
Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, New York 10021, USA.
Behav Brain Res. 1997 Jul;86(2):201-4. doi: 10.1016/s0166-4328(96)02257-7.
Cocaine administration causes dramatic stereotypic behavior and elevation of circulating corticosterone levels in rodents. The present study tested the possible role of increased corticosterone in mediating stereotypic behavior caused by "binge' pattern cocaine administration. Animals were administered saline or cocaine intraperitoneally for 3 days, with or without pretreatment with a D1 (SCH 23390, 2 mg/kg) or D2 (sulpiride, 50 mg/kg) dopamine receptor antagonist. Three days of cocaine "binges' significantly increased corticosterone levels in vehicle pretreated rats (P < 0.01). Both SCH 23390 and sulpiride pretreatment daily significantly attenuated this increase (P < 0.01). Cocaine administration caused stereotypic behaviors in vehicle pretreatment rats (P < 0.01). These behavioral responses were blocked by the D1 dopamine receptor antagonist SCH 23390, but not by the D2 antagonist sulpiride. These findings reaffirm the dominant role of the D1 receptor in mediating behavioral stereotypy caused by elevations of extracellular dopamine in the synaptic cleft. The fact that the dose of sulpiride used in these studies prevented the elevation of plasma corticosterone caused by cocaine, without blocking the stereotypy caused by cocaine, indicates that this stereotypic behavior does not require drug-induced elevation in circulating levels of corticosterone.
给予可卡因会导致啮齿动物出现剧烈的刻板行为，并使循环中的皮质酮水平升高。本研究测试了皮质酮增加在介导由“暴饮暴食”模式给予可卡因所引起的刻板行为中可能发挥的作用。给动物腹腔注射生理盐水或可卡因，持续3天，同时给予或不给予D1（SCH 23390，2毫克/千克）或D2（舒必利，50毫克/千克）多巴胺受体拮抗剂进行预处理。连续3天的可卡因“暴饮暴食”显著提高了用赋形剂预处理的大鼠的皮质酮水平（P<0.01）。每日给予SCH 23390和舒必利预处理均显著减弱了这种升高（P<0.01）。给予可卡因会使用赋形剂预处理的大鼠出现刻板行为（P<0.01）。这些行为反应被D1多巴胺受体拮抗剂SCH 23390阻断，但未被D2拮抗剂舒必利阻断。这些发现再次证实了D1受体在介导由突触间隙中细胞外多巴胺升高所引起的行为刻板症中起主导作用。在这些研究中使用的舒必利剂量能够防止可卡因引起的血浆皮质酮升高，但却不会阻断可卡因引起的刻板行为，这一事实表明这种刻板行为并不需要药物诱导循环中的皮质酮水平升高。
