An electrophysiological analysis of rat ventral tegmental dopamine neuronal activity during acute toluene exposure.
An electrophysiological analysis of rat ventral tegmental dopamine neuronal activity during acute toluene exposure.
复制标题
急性甲苯暴露期间大鼠腹侧被盖多巴胺神经元活动的电生理学分析。
DOI：
10.1111/j.1600-0773.1999.tb01061.x
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发表时间：
1999
期刊：
影响因子：
--
通讯作者：
French,ED
中科院分区：
文献类型：
--
作者：
Riegel,AC;French,ED
吸入性滥用是一种常见的、可能致命的药物滥用形式。虽然一些普遍滥用的吸入剂的假定精神成分似乎通常是有机溶剂甲苯，但其对包含奖赏通路的中脑神经元的影响尚未确定。因此，本研究旨在评估腹侧被盖多巴胺神经元在甲苯吸入过程中的反应。在氯胺酮麻醉大鼠中使用细胞外单单位记录进行电生理测定，这些大鼠暴露于急性（1-15.3分钟）甲苯蒸气的浓度（11，500 ppm）与吸入性滥用者所消耗的浓度相似。甲苯暴露通过气管呼吸管引起两个明显不同的模式，多巴胺神经元的反应。一种模式包括神经元放电的初始刺激（+221%至72%;<8.5分钟）。随后随着持续暴露，放电率衰减（+58.7%至6.3%; >8.5分钟）。另一种模式只包括抑制发射，而不管暴露的时间长短。此外，放电频率的变化被爆发中包含的动作电位数量的变化所掩盖。在多巴胺记录时采集的血样显示甲苯浓度相当（4-79 μg/ml，n=24），无论反应模式如何。这些结果表明，中脑边缘多巴胺神经传递可以改变暴露的范式，人类滥用者所使用的，这些变化可能是不可或缺的吸入剂滥用的增强作用。
Inhalant abuse is a common, potentially lethal, form of drug abuse. Although the putative psychotropic component of some popularly abused inhalants appears often to be the organic solvent toluene, its effects on midbrain neurones which comprise reward pathways have not been established. Therefore, the present study was designed to assess the response of ventral tegmental dopamine neurones during toluene inhalation. Electrophysiological determinations were made using extracellular single‐unit recordings in ketamine anaesthetized rats that were exposed to acute (1–15.3 min.) concentrations of toluene vapor (11,500 ppm) similar to those consumed by inhalant abusers. Toluene exposure through a tracheal breathing tube elicited two distinctly different patterns of response in dopamine neurons. One pattern consisted of an initial stimulation of neuronal firing (+221%±72%;<8.5 min.) followed by an attenuation of the firing rate with continued exposure (+58.7%±6.3%; >8.5 min.). The other pattern consisted of only an inhibition of firing regardless of the length of exposure. Furthermore, the changes in firing rates were paralleled by changes in number of action potentials contained in bursts. Blood samples taken at the time of the dopamine recordings revealed comparable toluene concentrations (4–79 μg/ml, n=24) regardless of the patterns of response. These results suggest that mesolimbic dopamine neurotransmission can be changed by an exposure paradigm comparable to that used by human abusers, and that these changes may be integral to the reinforcing effects underlying inhalant abuse.