Zhou Y, Spangler R, Ho A, Jeanne Kreek M
Laboratory of the Biology of Addictive Diseases, The Rockefeller University, New York, NY 10021, USA.
Brain Res Mol Brain Res. 2001 Oct 19;94(1-2):112-8. doi: 10.1016/s0169-328x(01)00223-6.
We previously found that there was a rapid stimulatory effect of acute (1 day) 'binge' cocaine on CRH mRNA levels in the rat hypothalamus. In contrast, after 3 days of 'binge' cocaine, there was a modest decrease (12%) in hypothalamic CRH mRNA levels, which after 14 days of 'binge' cocaine was greater (32%) and significantly lower than control values. Also, our previous studies found an elevation of CRH mRNA in the frontal cortex after 3 days of 'binge' cocaine. The present study was designed to investigate the possible role of dopamine receptors in modulating these effects. Administration of 3 days of 'binge' cocaine (3 x 15 mg/kg, i.p.) was preceded by daily injections of either D(1) (SCH23390, 2 mg/kg) or D(2) (sulpiride, 50 mg/kg) dopamine receptor antagonist. Neither SCH23390 nor sulpiride had an effect on basal CRH mRNA levels in the hypothalamus, frontal cortex or amygdala. Small decreases (10-13%) in hypothalamic CRH mRNA levels were found again to be induced by 3 days of repeated 'binge' cocaine. However, this modest decrease was not found in the rats that received D(1) antagonist SCH23390 pretreatment. Pretreatment with D(2) antagonist sulpiride had no effect on this decrease. These findings suggest that the inhibitory effect of repeated 'binge' cocaine on the hypothalamic CRH mRNA expression is absent when there is D(1), but not D(2), dopamine receptor blockade. In the frontal cortex, pretreatment with either SCH23390 or sulpiride did not alter the increases in the CRH mRNA levels induced by repeated 'binge' cocaine. The results suggest that the cocaine-induced modulation of hypothalamic CRH mRNA expression is secondary to changes in the activity of specific components of dopaminergic systems.
我们之前发现，急性（1天）“暴饮暴食”式可卡因给药对大鼠下丘脑促肾上腺皮质激素释放激素（CRH）mRNA水平有快速刺激作用。相比之下，“暴饮暴食”式可卡因给药3天后，下丘脑CRH mRNA水平有适度下降（12%），而在“暴饮暴食”式可卡因给药14天后，下降幅度更大（32%），且显著低于对照值。此外，我们之前的研究发现，“暴饮暴食”式可卡因给药3天后额叶皮质中CRH mRNA水平升高。本研究旨在探讨多巴胺受体在调节这些效应中可能发挥的作用。在给予3天“暴饮暴食”式可卡因（3×15毫克/千克，腹腔注射）之前，每日注射D(1)（SCH23390，2毫克/千克）或D(2)（舒必利，50毫克/千克）多巴胺受体拮抗剂。SCH23390和舒必利均对下丘脑、额叶皮质或杏仁核中的基础CRH mRNA水平无影响。再次发现，3天重复“暴饮暴食”式可卡因给药会诱导下丘脑CRH mRNA水平出现小幅下降（10 - 13%）。然而，在接受D(1)拮抗剂SCH23390预处理的大鼠中未发现这种适度下降。用D(2)拮抗剂舒必利预处理对此下降无影响。这些发现表明，当存在D(1)而非D(2)多巴胺受体阻断时，重复“暴饮暴食”式可卡因对下丘脑CRH mRNA表达的抑制作用不存在。在额叶皮质中，用SCH23390或舒必利预处理均未改变重复“暴饮暴食”式可卡因诱导的CRH mRNA水平升高。结果表明，可卡因诱导的下丘脑CRH mRNA表达调节是多巴胺能系统特定成分活性变化的继发效应。
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