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The brain gene expression profile of dopamine D2/D3 receptors and associated signaling proteins following amphetamine self-administration

机译：苯丙胺自我给药后多巴胺D2 / D3受体和相关信号蛋白的脑基因表达谱

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Persistent neuroadaptations following chronic psychostimulant exposure include reduced striatal dopamine D2 receptor (D2R) levels. The signaling of D2Rs is initiated by Gαi/o proteins and terminated by regulator of G protein signaling (RGS) proteins. The purpose of this study is to examine the association of the drug taking behavior and gene expression profile of D2/D3Rs, and their associated signaling proteins in the ventral tegmental area (VTA) and nucleus accumbens (NAc) using a rodent model of amphetamine (AMPH) self-administration. Rats were allowed to self-administer AMPH (0.187 mg/kg/infusion for a maximum of 40 injections in 6 hr daily sessions) for 5 days during which rats showed an escalated rate of AMPH intake across days. AMPH self-administration induced profound brain region-dependent alterations of the targeted genes. There was a positive correlation of the mRNA levels of RGS10 between the VTA and the NAc in the control animals, which was abolished by AMPH self-administration. AMPH self-administration also produced a negative correlation of the mRNA levels of RGS7 and RGS19 between the two brain regions, which was not present in the control group. Furthermore, AMPH taking behavior was associated with changes in certain gene expression. The mRNA levels of RGS2 and RGS4 in both the VTA and NAc were positively correlated with the rate of AMPH intake. Additionally, the rate of AMPH intake was also positively correlated with RGS10 and negatively correlated with RGS17 and the short form of D2Rs mRNA level in the VTA. Although there were significant changes in the mRNA levels of RGS7 and RGS8 in the NAc, none of these measures were correlated with the rate of AMPH intake. The present study suggested that short-term AMPH self-administration produced pronounced changes in the VTA that were more associated with AMPH taking behavior than changes in the NAc.
机译：慢性精神刺激剂暴露后持续的神经适应包括纹状体多巴胺D2受体（D2R）水平降低。 D2R的信号传导由Gαi/ o蛋白引发，并由G蛋白信号传导（RGS）蛋白的调节剂终止。这项研究的目的是使用苯丙胺（啮齿类动物）模型检查D2 / D3Rs的吸毒行为和基因表达谱及其在腹侧被盖区（VTA）和伏隔核（NAc）中的相关信号传导蛋白的关联AMPH）自我管理。允许大鼠自用AMPH（0.187 mg / kg /输液，每天6小时，最多40次注射），持续5天，在此期间，大鼠全天AMPH摄取率不断提高。 AMPH自我管理诱导了靶向基因的深刻脑区域依赖性改变。对照动物的VTA和NAc之间RGS10的mRNA水平呈正相关，而AMPH自我给药已将其消除。 AMPH自我给药还产生了两个大脑区域之间RGS7和RGS19 mRNA水平的负相关，而对照组中没有。此外，采取AMPH的行为与某些基因表达的变化有关。 VTA和NAc中RGS2和RGS4的mRNA水平与AMPH摄入率呈正相关。另外，AMPH中AMPH的摄取率也与RGS10正相关，与RGS17和D2Rs mRNA短形式负相关。尽管NAc中RGS7和RGS8的mRNA水平发生了显着变化，但这些指标均与AMPH摄入量无关。本研究表明，短期AMPH自我管理会在VTA中产生明显的变化，这与AMPH的服用行为比NAc的变化更相关。

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