Evidence for site specific ethanol actions in the CNS.

Alcohol and drug research Pub Date : 1985-01-01
T J McCown, G D Frye, G R Breese
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Abstract

The diverse behavioral and biochemical effects induced by ethanol suggest that ethanol exerts differential effects on the CNS. When the neuroactive amino acids, glycine, glutamate, aspartate, GABA and taurine, were measured in the cortex, striatum, hippocampus, midbrain, and brain stem of acute or chronic ethanol-treated rats, site specific changes were observed for glutamate, glycine, and aspartate. No changes were found for GABA or taurine. Upon in vivo application, it was found that the microinjection of thyrotropin-releasing hormone (TRH, 500 ng) into the medial septum significantly shortened ethanol's impairment of the righting reflex, while microinjection of muscimol (30 ng) markedly potentiated ethanol's impairment of the righting reflex. When these studies are combined with previous work showing that microinjection of muscimol (30 ng) into the inferior colliculus blocks audiogenically induced seizures in ethanol-withdrawn rats, the convergence implies that specific sites in the CNS may modulate certain actions of ethanol. Therefore, we propose that the medial septum and inferior colliculus can be used as in vivo models to study the acute and chronic actions of ethanol, respectively.

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乙醇在中枢神经系统中特异作用的证据。
乙醇诱导的多种行为和生化效应表明,乙醇对中枢神经系统有不同的影响。在急性或慢性乙醇处理大鼠的皮层、纹状体、海马、中脑和脑干中测定神经活性氨基酸甘氨酸、谷氨酸、天冬氨酸、GABA和牛磺酸,观察谷氨酸、甘氨酸和天冬氨酸的部位特异性变化。GABA和牛磺酸没有变化。经体内应用,发现内侧隔微量注射促甲状腺激素释放激素(TRH, 500 ng)可显著缩短乙醇对翻正反射的损害,而微量注射muscimol (30 ng)可显著增强乙醇对翻正反射的损害。当这些研究与先前的研究相结合时,表明向下丘微量注射muscimol (30 ng)可以阻断乙醇戒断大鼠的听源性癫痫发作,这表明中枢神经系统中的特定部位可能调节乙醇的某些作用。因此,我们建议将内隔和下丘分别作为体内模型来研究乙醇的急性和慢性作用。
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