Shen R Y, Hannigan J H, Kapatos G
Department of Psychiatry, Wayne State University School of Medicine, Detroit, Michigan, USA.
Alcohol Clin Exp Res. 1999 Nov;23(11):1801-7.
Prenatal ethanol exposure has been demonstrated to reduce dopamine (DA) neurotransmission in the forebrain area, which could be contributed by altered electrical activity in midbrain DA neurons. This hypothesis was tested in the present study.
The effects of prenatal ethanol exposure on the spontaneous activity of DA neurons in the substantia nigra and ventral tegmental area were investigated with extracellular single-unit recording techniques in adult male rats. Pregnant rats were administered single daily doses of 0, 3, or 5 g/kg ethanol via intragastric intubation from gestation day 8 through 20. An additional control group did not receive the intubation procedure.
Prenatal ethanol treatment significantly reduced the number of spontaneously active DA neurons in the substantia nigra and ventral tegmental area in 3- to 5-month-old male offspring. The firing rate and firing pattern of the remaining spontaneously active DA neurons were not altered. There were no differences in the spontaneous activity of DA neurons between the nonintubated and 0 g/kg control groups, indicating possible intubation-induced stress did not influence the activity of DA neurons in adult offspring. Similar prenatal ethanol effects were also determined from older animals (14-16 months old), suggesting that the reduction in the spontaneous activity of DA neurons is a persistent phenomenon in adulthood after prenatal ethanol exposure. Furthermore, the reduction in the number of spontaneously active DA neurons was not the result of a loss in DA neurons per se, as revealed by the results of tyrosine hydroxylase immunohistochemistry. The prenatal ethanol exposure-induced reduction in DA neuronal activity may result from depolarization inactivation, because systemically administered apomorphine (20 microg) increased the spontaneous activity of DA neurons.
Prenatal ethanol exposure induced a long-lasting reduction in the activity of midbrain DA neurons in adult animals. The effect was not the result of cell loss but possible changes in the electrical properties of DA neurons. The decreased electrical activity in midbrain DA neurons could contribute to the prenatal ethanol exposure-induced reduction in DA content and metabolites observed in previous studies and the attention/hyperactivity problems reported in children with fetal alcohol effects/fetal alcohol syndrome.
产前乙醇暴露已被证明会降低前脑区域的多巴胺（DA）神经传递，这可能是中脑DA神经元电活动改变所致。本研究对这一假设进行了验证。
采用细胞外单单位记录技术，研究产前乙醇暴露对成年雄性大鼠黑质和腹侧被盖区DA神经元自发活动的影响。从妊娠第8天至第20天，对怀孕大鼠每天经胃内插管给予0、3或5 g/kg乙醇单剂量。另一个对照组未接受插管操作。
产前乙醇处理显著减少了3至5月龄雄性后代黑质和腹侧被盖区自发活动的DA神经元数量。其余自发活动的DA神经元的放电频率和放电模式未改变。未插管对照组和0 g/kg对照组之间DA神经元的自发活动没有差异，表明插管引起的应激可能不会影响成年后代DA神经元的活动。在年龄较大的动物（14至16个月大）中也确定了类似的产前乙醇效应，这表明产前乙醇暴露后，DA神经元自发活动的减少在成年期是一种持续现象。此外，酪氨酸羟化酶免疫组化结果显示，自发活动的DA神经元数量减少并非DA神经元本身丢失的结果。产前乙醇暴露引起的DA神经元活动减少可能是去极化失活所致，因为全身给予阿扑吗啡（20微克）可增加DA神经元的自发活动。
产前乙醇暴露导致成年动物中脑DA神经元活动长期减少。这种影响不是细胞丢失的结果，而是DA神经元电特性可能发生的变化。中脑DA神经元电活动的降低可能导致先前研究中观察到的产前乙醇暴露引起的DA含量和代谢产物减少，以及胎儿酒精效应/胎儿酒精综合征儿童中报告的注意力/多动问题。
