Numan S, Lundgren K H, Wright D E, Herman J P, Seroogy K B
Department of Anatomy and Neurobiology, University of Kentucky, Lexington 40536, USA.
Brain Res Mol Brain Res. 1995 Apr;29(2):391-6. doi: 10.1016/0169-328x(95)00004-c.
Neonatal destruction of the dopaminergic nigrostriatal system with the specific neurotoxin 6-hydroxydopamine (6-OHDA) leads to increases in several components of the adult serotonergic raphe-striatal system. Although results following similar lesions of adult ventral midbrain dopaminergic neurons are less consistent, increases in striatal serotonin (5-hydroxytryptamine; 5HT) fiber density, content, and metabolites have been reported. The effect of such lesions upon gene expression for striatal 5HT receptors, however, has not been determined. The purpose of the present study was to investigate possible changes in expression of several 5HT receptor mRNAs in rat striatum following destruction of the adult nigrostriatal pathway. In situ hybridization for 5HT1A, 5HT1C, and 5HT2 receptor subtype mRNAs was performed in rat striatum following unilateral injection of 6-OHDA into the medial forebrain bundle or directly into the ventral midbrain. Compared to the uninjected control side, a significant increase in the hybridization density for 5HT2 receptor mRNA was observed in the caudate-putamen ipsilateral to the 6-OHDA lesion (P < 0.05). In contrast, no significant changes in the hybridization densities for 5HT1A or 5HT1C receptor mRNAs were detected. The observed increase in striatal 5HT2 receptor mRNA levels after the dopamine-depleting lesion provides evidence for plasticity of the serotonergic raphe-striatal system in the adult rat at the level of striatal gene expression. Furthermore, the present data indicate that dopaminergic mechanisms differentially regulate the expression of 5HT receptor mRNAs in adult rat striatum.
用特定神经毒素6-羟基多巴胺（6-OHDA）对新生鼠多巴胺能黑质纹状体系统进行破坏，会导致成年血清素能中缝核-纹状体系统的多个成分增加。尽管对成年腹侧中脑多巴胺能神经元进行类似损伤后的结果不太一致，但已有报道称纹状体血清素（5-羟色胺；5HT）纤维密度、含量和代谢产物有所增加。然而，此类损伤对纹状体5HT受体基因表达的影响尚未确定。本研究的目的是调查成年黑质纹状体通路被破坏后，大鼠纹状体中几种5HT受体mRNA表达的可能变化。在将6-OHDA单侧注射到内侧前脑束或直接注射到腹侧中脑后，对大鼠纹状体进行5HT1A、5HT1C和5HT2受体亚型mRNA的原位杂交。与未注射的对照侧相比，在6-OHDA损伤同侧的尾状核-壳核中观察到5HT2受体mRNA的杂交密度显著增加（P < 0.05）。相比之下，未检测到5HT1A或5HT1C受体mRNA的杂交密度有显著变化。多巴胺耗竭性损伤后纹状体5HT2受体mRNA水平的增加，为成年大鼠血清素能中缝核-纹状体系统在纹状体基因表达水平上的可塑性提供了证据。此外，目前的数据表明，多巴胺能机制对成年大鼠纹状体中5HT受体mRNA的表达有不同的调节作用。
