Zhang Y, Angulo J A
Department of Biological Sciences, Hunter College of the City University of New York, New York 10021, USA.
Synapse. 1996 Nov;24(3):218-23. doi: 10.1002/(SICI)1098-2396(199611)24:3<218::AID-SYN3>3.0.CO;2-H.
We have assessed the effect of repeated treatment with methamphetamine (METH) on the abundance of the messenger ribonucleic acid molecules encoding the enzyme tyrosine hydroxylase (TH) and preprocholecystokinin (PPCCK) in the substantia nigra zona compacta (SNc) and the ventral tegmental area (VTA) by in situ hybridization histochemistry. Rats were injected twice daily with METH (4 mg/kg of body weight) for 6 consecutive days and sacrificed either 5 h or 15 days after the last injection. TH mRNA in the VTA was unaffected by repeated METH treatment but was decreased 25% relative to controls in the SNc. Concurrent administration of METH and MK-801 decreased TH mRNA levels in the SNc to 47% relative to controls. In contrast, TH mRNA levels were found increased in the VTA (42%) but not SNc 15 days post-METH treatment. Coadministration of MK-801 with METH prevented the increase in TH mRNA in the VTA. PPCCK mRNA levels were not significantly affected by METH treatment in VTA or SNc either 5 h or 15 days posttreatment. The results demonstrate that exposure to repeated methamphetamine elicits changes of TH mRNA levels in the VTA that become manifest 2 weeks after withdrawal from this psychostimulant drug.
我们通过原位杂交组织化学技术评估了重复给予甲基苯丙胺（METH）对黑质致密部（SNc）和腹侧被盖区（VTA）中编码酪氨酸羟化酶（TH）和前胆囊收缩素原（PPCCK）的信使核糖核酸分子丰度的影响。大鼠连续6天每天注射两次METH（4mg/kg体重），并在最后一次注射后5小时或15天处死。VTA中的TH mRNA不受重复METH处理的影响，但相对于对照组，SNc中的TH mRNA降低了25%。同时给予METH和MK-801可使SNc中的TH mRNA水平相对于对照组降至47%。相反，在METH处理后15天，VTA中的TH mRNA水平升高（42%），而SNc中未升高。MK-801与METH共同给药可防止VTA中TH mRNA的升高。在处理后5小时或15天，VTA或SNc中的PPCCK mRNA水平均未受到METH处理的显著影响。结果表明，反复接触甲基苯丙胺会引发VTA中TH mRNA水平的变化，这种变化在停用这种精神刺激药物两周后变得明显。
