Wang J Q, McGinty J F
Department of Anatomy and Cell Biology, East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, USA.
Synapse. 1996 Feb;22(2):114-22. doi: 10.1002/(SICI)1098-2396(199602)22:2<114::AID-SYN4>3.0.CO;2-G.
Our previous work has demonstrated a dose-dependent induction of striatal preprodynorphin (PPD) in response to a single injection of the psychostimulants amphetamine (AMPH) or methamphetamine (METH). In the present study, dose-response effects of acute administration of these stimulants on preproenkephalin (PPE) mRNA expression in the rat striatum were investigated with quantitative in situ hybridization histochemistry 3 h after injection. Acute AMPH or METH at equimolar doses (3.75, 7.5, 15, and 30 mumol/kg) significantly increased PPE mRNA expression in dorsal (caudoputamen), but not ventral (nucleus accumbens), striatum in a dose-dependent fashion. In addition, the role of D1 and D2 dopamine receptors in mediating AMPH- and METH-stimulated PPE and PPD expression was also evaluated by using subtype-specific antagonists. Pretreatment of rats with SCH 23390 (0.1 mg/kg, i.p.), a selective D1 receptor antagonist, completely blocked acute AMPH (21 mumol/kg, i.p.)- or METH (21 mumol/kg, i.p.)-induced PPE as well as PPD mRNA expression in the caudoputamen. Pretreatment with eticlopride (0.5 mg/kg, i.p.), a selective D2 receptor antagonist, also blocked PPD induction by the two stimulants, but PPE induction was unaffected. Furthermore, SCH 23390 decreased, and eticlopride elevated, constitutive PPE mRNA levels in the caudoputamen. Neither antagonist had a significant effect on the basal level of PPE or PPD mRNA in the nucleus accumbens. These results demonstrate a clear dose-related responsiveness of PPE gene expression in striatal neurons in response to acute administration of amphetamines, although the intensity of the response is far less than that for striatal PPD. Furthermore, both D1 and D2 subtypes of dopamine receptors mediate AMPH- and METH-stimulated striatal PPD mRNA expression, whereas D1 receptor activation alone mediates amphetamine-stimulated PPE mRNA expression in the rat striatum.
我们之前的研究表明，单次注射精神兴奋剂苯丙胺（AMPH）或甲基苯丙胺（METH）后，纹状体前强啡肽原（PPD）的诱导呈剂量依赖性。在本研究中，注射3小时后，采用定量原位杂交组织化学方法研究了这些兴奋剂急性给药对大鼠纹状体前脑啡肽原（PPE）mRNA表达的剂量反应效应。等摩尔剂量（3.75、7.5、15和30μmol/kg）的急性AMPH或METH以剂量依赖性方式显著增加了背侧（尾壳核）而非腹侧（伏隔核）纹状体中的PPE mRNA表达。此外，还通过使用亚型特异性拮抗剂评估了D1和D2多巴胺受体在介导AMPH和METH刺激的PPE和PPD表达中的作用。用选择性D1受体拮抗剂SCH 23390（0.1mg/kg，腹腔注射）预处理大鼠，可完全阻断急性AMPH（21μmol/kg，腹腔注射）或METH（21μmol/kg，腹腔注射）诱导的尾壳核中PPE以及PPD mRNA的表达。用选择性D2受体拮抗剂依替必利（0.5mg/kg，腹腔注射）预处理也可阻断这两种兴奋剂诱导的PPD表达，但PPE诱导不受影响。此外，SCH 23390降低了尾壳核中组成型PPE mRNA水平，而依替必利则升高了该水平。两种拮抗剂对伏隔核中PPE或PPD mRNA的基础水平均无显著影响。这些结果表明，尽管反应强度远低于纹状体PPD，但纹状体神经元中PPE基因表达对苯丙胺急性给药有明显的剂量相关反应性。此外，多巴胺受体的D1和D2亚型均介导AMPH和METH刺激的纹状体PPD mRNA表达，而仅D1受体激活介导大鼠纹状体中苯丙胺刺激的PPE mRNA表达。
