Dopaminergic neurons in the ventral tegmental area of C57BL/6J and DBA/2J mice differ in sensitivity to ethanol excitation
Dopaminergic neurons in the ventral tegmental area of C57BL/6J and DBA/2J mice differ in sensitivity to ethanol excitation
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DOI：
10.1111/j.1530-0277.2000.tb04658.x
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发表时间：
2000-07-01
影响因子：
3.2
通讯作者：
Appel, SB
中科院分区：
文献类型：
--
作者：
Brodie, MS;Appel, SB
背景：起源于腹侧被盖区（VTA）的中脑边缘多巴胺通路对于乙醇的奖励作用很重要。在大鼠体内和体外，乙醇已被证明可以兴奋 VTA 的多巴胺能神经元。在 C57BL/6J 和 DBA/2J 小鼠之间观察到乙醇奖励效应的行为差异。本电生理学研究检查了乙醇对这两种近交小鼠品系的单个多巴胺能 VTA 神经元的影响。方法：从 C57BL/6J 或 DBA/2J 小鼠脑切片中的多巴胺能 VTA 神经元进行自发动作电位的细胞外单单位记录。将乙醇（10至160 mM）注入过液中，并测量乙醇产生的放电率的平均变化。结果：这两种小鼠品系的多巴胺能VTA神经元的基础自发放电率没有显着差异。乙醇导致两种小鼠品系的神经元放电率呈浓度依赖性增加。乙醇对 DBA/2J 小鼠多巴胺能 VTA 神经元的兴奋作用仅强于 C57BL/6J 小鼠。结论：C57BL/6J 和 DBA/2J 小鼠中多巴胺能 VTA 神经元对乙醇兴奋的敏感性差异可能导致其对乙醇的行为反应差异。给定浓度的乙醇会导致 DBA/2J 小鼠的多巴胺能 VTA（奖赏）神经元比 C57BL/6J 小鼠更大的兴奋，这一事实可以解释为什么 DBA/2J 小鼠在乙醇作用下表现出更强的位置偏好调节。 C57BL/6J 小鼠自愿摄入乙醇较高的部分原因可能是其多巴胺能 VTA 神经元不敏感，需要饮用大量乙醇才能充分激发奖赏神经元，而 DBA/2J 小鼠则避免口服乙醇，尽管它有奖赏作用，因为它们厌恶乙醇的味道。
Background: The mesolimbic dopamine pathway that originates in the ventral tegmental area (VTA) is important for the rewarding effects of ethanol. Ethanol has been shown to excite dopaminergic neurons of the VTA both in vivo and in vitro, in rats. Behavioral differences in the rewarding effects of ethanol have been observed between C57BL/6J and DBA/2J mice. The present electrophysiological study examined the effect of ethanol on individual dopaminergic VTA neurons from these two inbred mouse strains.Methods: Extracellular single unit recordings of spontaneous action potentials were made from dopaminergic VTA neurons in brain slices from either C57BL/6J or DBA/2J mice. Ethanol (10 to 160 mM) was administered in the superfusate and the mean change in firing rate produced by ethanol was measured.Results: There was no significant difference in basal spontaneous firing rate of dopaminergic VTA neurons between these two mouse strains. Ethanol caused a concentration-dependent increase in the firing rate of neurons from both mouse strains. Ethanol excited dopaminergic VTA neurons from DBA/2J mice mere potently than those from C57BL/6J mice.Conclusions: The difference in sensitivity to ethanol excitation of dopaminergic VTA neurons in C57BL/6J and DBA/2J mice may contribute to differences in their behavioral response to ethanol. The fact that a given concentration of ethanol causes greater excitation of dopaminergic VTA (reward) neurons in DBA/2J mice than in C57BL/6J mice could explain why DBA/2J mice show much stronger place preference conditioning with ethanol. The higher voluntary intake of ethanol by C57BL/6J mice may be partly due to the insensitivity of their dopaminergic VTA neurons that requires them to drink a lot of ethanol to achieve sufficient excitation of reward neurons, whereas DBA/2J mice avoid oral ingestion of ethanol, despite its rewarding effect, because of their aversion to its taste.