Correlation between ethanol behavioral sensitization and midbrain dopamine neuron reactivity to ethanol
Correlation between ethanol behavioral sensitization and midbrain dopamine neuron reactivity to ethanol
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DOI：
10.1111/adb.12216
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发表时间：
2016-03-01
影响因子：
3.4
通讯作者：
Quertemont, Etienne
中科院分区：
文献类型：
--
作者：
Didone, Vincent;Masson, Sebastien;Quertemont, Etienne
反复注射乙醇会导致小鼠对乙醇的刺激作用变得敏感。最近的一些结果反对腹侧被盖区(VTA)多巴胺神经元在酒精行为敏化中的作用。本研究的目的是测试体内乙醇运动敏化是否与体外基础或乙醇诱发的多巴胺神经元放电频率的变化相关。雌性瑞士小鼠每天注射2.5g/kg乙醇(对照组为生理盐水)，连续7d，记录其运动活动。在致敏过程结束时，对这些小鼠中脑片中的多巴胺能神经元进行细胞外记录。与对照组相比，乙醇致敏小鼠的多巴胺神经元自发基础放电频率显著增加，但与行为效应无关。灌流多巴胺D2拮抗剂舒必利后，乙醇致敏小鼠多巴胺神经元放电频率明显增加。这表明，在长期服用乙醇后，多巴胺神经元中的D2反馈被保留下来，并反对将减少的D2反馈作为乙醇致敏小鼠多巴胺神经元基础放电频率增加的解释。最后，乙醇灌流(10-100 mM)可显著增加多巴胺神经元的放电频率，这种作用在乙醇致敏的小鼠中更为明显。此外，多巴胺神经元活动的这种敏化与酒精行为敏化之间存在显著的相关性。这些结果支持这样一种假设，即大脑多巴胺神经元活动的变化有助于乙醇刺激效应的行为敏化。
Repeated ethanol injections lead to a sensitization of its stimulant effects in mice. Some recent results argue against a role for ventral tegmental area (VTA) dopamine neurons in ethanol behavioral sensitization. The aim of the present study was to test whether in vivo ethanol locomotor sensitization correlates with changes in either basal- or ethanol-evoked firing rates of dopamine neurons in vitro. Female Swiss mice were daily injected with 2.5g/kg ethanol (or saline in the control group) for 7 days and their locomotor activity was recorded. At the end of the sensitization procedure, extracellular recordings were made from dopaminergic neurons in midbrain slices from these mice. Significantly higher spontaneous basal firing rates of dopamine neurons were recorded in ethanol-sensitized mice relative to control mice, but without correlations with the behavioral effects. The superfusion of sulpiride, a dopamine D2 antagonist, induced a stronger increase of dopamine neuron firing rates in ethanol-sensitized mice. This shows that the D2 feedback in dopamine neurons is preserved after chronic ethanol administration and argues against a reduced D2 feedback as an explanation for the increased dopamine neuron basal firing rates in ethanol-sensitized mice. Finally, ethanol superfusion (10-100mM) significantly increased the firing rates of dopamine neurons and this effect was of higher magnitude in ethanol-sensitized mice. Furthermore, there were significant correlations between such a sensitization of dopamine neuron activity and ethanol behavioral sensitization. These results support the hypothesis that changes in brain dopamine neuron activity contribute to the behavioral sensitization of the stimulant effects of ethanol.