Microinjections of acetaldehyde or salsolinol into the posterior ventral tegmental area increase dopamine release in the nucleus accumbens shell.

Microinjections of acetaldehyde or salsolinol into the posterior ventral tegmental area increase dopamine release in the nucleus accumbens shell.
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DOI:
10.1111/acer.12034
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发表时间:
2013-05
期刊:
Alcoholism, clinical and experimental research
影响因子:
--
通讯作者:
Rodd ZA
Rodd ZA
中科院分区:
其他
文献类型:
--
作者:
Deehan GA Jr;Engleman EA;Ding ZM;McBride WJ;Rodd ZA

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已发表的研究结果表明,在乙醇(EtOH)消耗后,可以形成乙醛(ACD, EtOH的第一个代谢物)和salsolinol (SAL,通过ACD和多巴胺的非酶缩合形成)。ACD和SAL均在后腹侧被盖区(pVTA)内表现出增强特性,且均呈现倒“u”型剂量-反应曲线。本研究旨在研究向pVTA内微注射ACD或SAL对伏隔核壳(AcbSh)内DA外排的剂量反应效应。在第一个实验中,各组雄性Wistar大鼠分别在pVTA中脉冲注射aCSF或12、23或90µM ACD,同时在AcbSh中测量细胞外DA水平。第2个实验与第2个实验相似,只给大鼠微注射aCSF或0.03、0.3、1.0或3.0µM SAL,同时在AcbSh中测定胞外DA水平。ACD和SAL在AcbSh中对DA释放均产生剂量依赖的倒“u”型反应,其中23µM ACD(200%基线)和0.3µM SAL(300%基线)产生最大峰值反应,较高浓度ACD(90µM)和SAL(3.0µM)产生明显较低的DA外排。目前的研究结果表明,局部应用中等浓度的ACD和SAL刺激pVTA中的DA神经元,而高浓度的ACD和SAL可能在pVTA内产生抑制DA神经元活动的次级效应。本研究平行研究了ACD和SAL在pVTA内的强化作用,支持了ACD和SAL在pVTA内的强化作用是通过激活DA神经元介导的。
Published findings indicate that acetaldehyde (ACD; the first metabolite of EtOH) and salsolinol (SAL; formed through the non-enzymatic condensation of ACD and dopamine) can be formed following ethanol (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 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 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.
DOI: 10.1007/s00213-005-0224-z
发表时间: 2006-01-01
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DOI: 10.1097/01.alc.0000171945.30494.af
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影响因子: 3.2
作者:
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