Mathieu-Kia A M, Besson M J
Laboratoire de Neurochimie-Anatomie, Institut des Neurosciences, CNRS URA 1488, Université Pierre et Marie Curie, Paris, France.
Brain Res Mol Brain Res. 1998 Feb;54(1):141-51. doi: 10.1016/s0169-328x(97)00338-0.
It is established that dopamine (DA) controls the expression of preprodynorphin (PPDYN), preprotachykinin A (PPT-A) and preproenkephalin (PPE) mRNAs in striatal structures. Since cocaine, nicotine and ethanol enhance extracellular DA concentration, we have examined whether their repeated administration produced common changes in the expression of these mRNAs. Quantitative in situ hybridization histochemistry was performed in rats 2 h after a final challenge subsequent to repeated subcutaneous injections (3 X a day) of cocaine (12.5 mg/kg), nicotine (0.4 mg/kg) for 14 days and ethanol (160 mg/kg) for 7 days. In the dorsal striatum, cocaine produced simultaneous PPDYN and PPT-A mRNA increases without PPE mRNA change whereas nicotine and ethanol produced no modification. After cocaine, PPDYN mRNA was preferentially increased in striatal patch compartment. In the nucleus accumbens, the effects were more complex. In cocaine-treated rats, we measured concomitant increases of PPDYN and PPE mRNA in the rostral pole, an isolated induction of PPT-A mRNA signals in the core without any change in the two shell subregions: the cone and the ventral shell. In contrast, after nicotine and ethanol, the ventral shell was the only accumbal subregion which showed a neuropeptide mRNA alteration, nicotine leading to decreased PPDYN mRNA and ethanol to increased PPT-A mRNA contents. The neuropeptide regulation after chronic treatment with these psychostimulant drugs does not strictly conform to a general DA control scheme in the dorsal and the ventral striatum. The cocaine effects can be clearly distinguished from those of nicotine and ethanol in terms of neuropeptide regulation and striatal subregions affected.
已证实多巴胺（DA）可控制纹状体结构中前强啡肽原（PPDYN）、前速激肽原A（PPT-A）和前脑啡肽原（PPE）mRNA的表达。由于可卡因、尼古丁和乙醇会提高细胞外DA浓度，我们研究了重复给予这些物质是否会对这些mRNA的表达产生共同影响。在大鼠皮下重复注射（每天3次）可卡因（12.5mg/kg）、尼古丁（0.4mg/kg），持续14天，以及乙醇（160mg/kg），持续7天后，于末次给予刺激2小时后进行定量原位杂交组织化学检测。在背侧纹状体中，可卡因使PPDYN和PPT-A mRNA同时增加，而PPE mRNA无变化，而尼古丁和乙醇则无影响。给予可卡因后，PPDYN mRNA在纹状体斑块区优先增加。在伏隔核中，影响更为复杂。在可卡因处理的大鼠中，我们发现吻侧极的PPDYN和PPE mRNA同时增加，核心区单独诱导PPT-A mRNA信号增加，而两个壳区（锥体和腹侧壳）无变化。相反，给予尼古丁和乙醇后，腹侧壳是伏隔核中唯一显示神经肽mRNA改变的亚区，尼古丁导致PPDYN mRNA减少，乙醇导致PPT-A mRNA含量增加。这些精神兴奋药物长期治疗后的神经肽调节并不严格符合背侧和腹侧纹状体中的一般DA控制模式。就神经肽调节和受影响的纹状体亚区而言，可卡因的作用可与尼古丁和乙醇的作用明显区分开来。
