Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Alcohol Clin Exp Res. 2013 May;37(5):722-9. doi: 10.1111/acer.12034. Epub 2012 Dec 20.
Published findings indicate that acetaldehyde (ACD; the first metabolite of ethanol [EtOH]) and salsolinol (SAL; formed through the nonenzymatic condensation of ACD and dopamine [DA]) can be formed following EtOH consumption. Both ACD and SAL exhibit reinforcing properties within the posterior ventral tegmental area (pVTA) and both exhibit an inverted "U-shaped" dose-response curve. The current study was undertaken to examine the dose-response effects of microinjections of ACD or SAL into the pVTA on DA efflux in the nucleus accumbens shell (AcbSh).
For the first experiment, separate groups of male Wistar rats received pulse microinjections of artificial cerebrospinal fluid (aCSF) or 12-, 23-, or 90-μM ACD into the pVTA, while extracellular DA levels were concurrently measured in the AcbSh. The second experiment was similarly conducted, except rats were given microinjections of aCSF or 0.03-, 0.3-, 1.0-, or 3.0-μM SAL, while extracellular levels of DA were measured in the AcbSh.
Both ACD and SAL produced a dose-dependent inverted "U-shaped" response on DA release in the AcbSh, with 23-μM ACD (200% baseline) and 0.3-μM SAL (300% baseline) producing maximal peak responses with higher concentrations of ACD (90 μM) and SAL (3.0 μM) producing significantly lower DA efflux.
The findings from the current study indicate that local application of intermediate concentrations of ACD and SAL stimulated DA neurons in the pVTA, whereas higher concentrations may be having secondary effects within the pVTA that inhibit DA neuronal activity. The present results parallel the studies on the reinforcing effects of ACD and SAL in the pVTA and support the idea that the reinforcing effects of ACD and SAL within the pVTA are mediated by activating DA neurons.
已发表的研究结果表明,乙醛(ACD;乙醇[EtOH]的第一代谢物)和索洛辛醇(SAL;通过 ACD 和多巴胺[DA]的非酶缩合形成)可在乙醇消耗后形成。ACD 和 SAL 均在后腹侧被盖区(pVTA)表现出强化特性,且均表现出倒“U”形剂量反应曲线。本研究旨在检查 ACD 或 SAL 微注射到 pVTA 对伏隔核壳(AcbSh)中 DA 外排的剂量反应效应。
在第一个实验中,雄性 Wistar 大鼠的不同组分别接受脉冲微注射人工脑脊液(aCSF)或 12-、23-或 90-μM ACD 到 pVTA,同时在 AcbSh 中同时测量细胞外 DA 水平。第二个实验类似进行,只是大鼠接受 aCSF 或 0.03-、0.3-、1.0-或 3.0-μM SAL 的微注射,同时在 AcbSh 中测量细胞外 DA 水平。
ACD 和 SAL 均在 AcbSh 中产生剂量依赖性倒“U”形 DA 释放反应,23-μM ACD(200%基线)和 0.3-μM SAL(300%基线)产生最大峰值反应,而更高浓度的 ACD(90 μM)和 SAL(3.0 μM)则导致 DA 外排明显降低。
本研究的结果表明,中间浓度的 ACD 和 SAL 局部应用刺激 pVTA 中的 DA 神经元,而更高浓度的 ACD 和 SAL 可能在 pVTA 中产生二次效应,抑制 DA 神经元活性。目前的结果与 ACD 和 SAL 在 pVTA 中的强化效应研究相吻合,并支持 ACD 和 SAL 在 pVTA 中的强化效应是通过激活 DA 神经元介导的观点。