目的探讨海洛因依赖对大鼠中脑腹侧被盖区(VTA)、伏隔核(NAc)神经元P物质(SP)、神经肽Y(NPY)表达的影响,为进一步揭示海洛因依赖的中枢机制提供重要的原位形态学资料。方法成年雄性SD大鼠55只,随机分为海洛因依赖组、生理盐水对照组及正常对照组。建立海洛因依赖模型,并分别于第10、17、24、31、38天取脑组织,免疫组织化学SABC法显示VTA、NAc区神经元SP、NPY免疫反应细胞并用图像分析法测定平均灰度值。结果海洛因依赖组VTA、NAc区的SP、NPY免疫反应细胞与生理盐水及正常对照组比较,免疫反应强度明显减弱、染色变浅。平均灰度值测定,海洛因依赖组各时间点大鼠VTA、NAc区的SP、NPY免疫反应细胞平均灰度值均高于正常对照组及生理盐水对照组,差异有统计学意义(P〈0.05)。结论实验结果提示,海洛因依赖使VTA、NAc区SP、NPY的分泌受到抑制,可能导致内源性阿片肽的分泌受影响,SP、NPY可能是药物依赖形成机制中的关键信号分子。
Objective To investigate the effect of the heroin addicts on substance P (SP), neuropeptide Y (NPY) immunoreactive cells in the ventral tegmental area (VTA) and nucleus accumbens (NAc) neurons of the rat brain, and to explore the central mechanisms of heroin dependence and to provide experimental and theoretical basis. Methods Fifty-five adult male SD rats were randomly divided into heroin dependence group (HDG), saline control group (SCG) and normal control group (NCG). Rats were chronically treated by injection of heroin for up to 38 days, and brain tissues were excised on the 10th, 17th, 24th, 31st, and 38th day after models were set up. Immunohistochemical SABC method, and image analysis were performed to test the expression of SP and NPY in the VTA and NAc regions. Results SP immunoreactive cells and NPY immunoreactive cells expressed less SP and NPY in the VTA and NAc regions from heroin dependence rats than that from saline control and normal control rats at different time points. Immunohistochemical analysis showed that the grey value was found higher in heroin dependence rats than that in controls ( P 〈 0. 05 ). Conclusion The secretion of SP and NPY is inhibited during heroin dependence and it may result in the inhibition of endogenous opioid peptides, suggesting that SP and NPY may be the key molecules during drug addiction.