The susceptibility of rat non-dopamine ventral tegmental neurones to inhibition during toluene exposure.
The susceptibility of rat non-dopamine ventral tegmental neurones to inhibition during toluene exposure.
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甲苯暴露期间大鼠非多巴胺腹侧被盖神经元对抑制的敏感性。
DOI：
10.1111/j.1600-0773.1999.tb01062.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
在过去的四十年中，许多学科已经在滥用药物的强化作用与连接中脑腹侧被盖和腹侧纹状体的中脑边缘多巴胺前脑通路中的神经传递改变之间建立了明确的关联（Koob 1992）。最近的数据也将这种相关性扩展到吸入剂滥用，指出常见的有机成分甲苯是推动其强化作用的活性成分之一。例如，人类滥用纯甲苯的实例证实了现有的行为数据，即灵长类动物也会为接触甲苯蒸气而工作（韦斯等人）。1979; Yamanouchi et ul. 1995年）。与精神兴奋剂可卡因和安非他明一样，甲苯对大鼠运动活性的增强作用可通过给予选择性多巴胺受体拮抗剂而减弱（里格尔& French 1999 a）。此外，纹状体（一种接受中脑边缘输入的结构）中的微透析取样发现甲苯增加多巴胺释放（StengBrd et ul. 1994年）。最后，大鼠腹侧被盖区多巴胺神经元的电生理记录显示，在甲苯吸入过程中，神经元活动升高（里格尔& French 1999 b）。因此，这些数据支持甲苯、中脑边缘多巴胺系统和吸入剂的奖励特性之间的关联。然而，他们仍然没有提供足够的证据的网站或甲苯兴奋多巴胺能活性的作用机制。虽然未经证实，一个可能的解释涉及腹侧被盖区固有的GABA能中间神经元。已知这些局部抑制性神经元可减少A10多巴胺细胞放电（Kalivas 1993）。因此，甲苯通过限制这些中间神经元的调节作用，可以通过一种失活机制引起多巴胺细胞的刺激。这种假设并非没有根据。事实上，
Over the past four decades, a number of disciplines have established a clear association between the reinforcing effects of abused drugs and alterations in neurotransmission in the mesolimbic dopamine forebrain pathway connecting the midbrain ventral tegmentum to the ventral striatum (Koob 1992). Recent data extended this correlation to inhalant abuse as well, pinpointing the common organic component, toluene, as one of the active ingredients driving its reinforcing effects. For example, instances of humans abusing pure toluene corroborate existing behavioural data that primates will also work for access to toluene vapour (Weiss et ul. 1979; Yamanouchi et ul. 1995). Like the psychomotor stimulants, cocaine and amphetamine, toluene's enhancement of rat locomotor activity is attenuated by the administration of a selective dopamine receptor antagonist (Riegel & French 1999a). Moreover, microdialysis sampling in the striatum, a structure receiving mesolimbic input, found that toluene increased dopamine release (StengBrd et ul. 1994). Finally, electrophysiological recordings from rat ventral tegmental area dopamine neurones showed elevations of neuronal activity during toluene inhalation (Riegel & French 1999b).These data, therefore, support an association between toluene, the mesolimbic dopamine system and the rewarding properties of inhalants. However, they still do not provide sufficient evidence of a site or mechanism of action by which toluene excites dopaminergic activity. Although untested, one possible explanation involves the GABAergic interneurons intrinsic to the ventral tegmental area. These local inhibitory neurones are known to curtail A10 dopamine cell firing (Kalivas 1993). Thus, toluene by restricting the modulating effect of these interneurones could elicit the stimulation of dopamine cells through a mechansim of disinhibiton. Such a hypothesis is not without basis. In fact,