Verbanck P, Seutin V, Massotte L, Dresse A
Medical Psychology Laboratory, Université Libre de Bruxelles, Belgium.
Alcohol Clin Exp Res. 1991 Dec;15(6):1036-9. doi: 10.1111/j.1530-0277.1991.tb05207.x.
Noradrenergic neurons have been implicated in the development of ethanol dependence and tolerance. Moreover, the development of an hyposensitivity of alpha 2 adrenoceptors has been postulated during long-term exposition to ethanol. In order to test the putative role of alpha 2 receptors in ethanol intoxication, we have studied the interaction between ethanol and yohimbine, an alpha 2 antagonist, on the spontaneous firing rate of rat locus coeruleus (LC) in an in vitro slice model. The spikes from single neurons were recorded by glass microelectrodes. Ethanol at 100 mM, a concentration that parallels the behavioral effects in the human and in the animals, inhibits the firing activity of some LC cells. This inhibition was quickly reversed after stopping the ethanol perfusion and was observed for each further administration. However, if yohimbine (20 microM) was simultaneously perfused, the ethanol-induced inhibition was rapidly antagonized. This effect is reversible after long time washout of yohimbine. This suggests that alpha 2 adrenoceptors could be implicated in the inhibitory effect of ethanol on LC noradrenergic neurons and perhaps in the development of tolerance. However, other hypotheses are discussed, because yohimbine can also antagonize other types of receptors.
去甲肾上腺素能神经元与乙醇依赖和耐受性的发展有关。此外，长期接触乙醇期间，有人推测α2肾上腺素能受体会出现低敏现象。为了测试α2受体在乙醇中毒中的假定作用，我们在体外脑片模型中研究了乙醇与α2拮抗剂育亨宾对大鼠蓝斑（LC）自发放电率的相互作用。用玻璃微电极记录单个神经元的放电。100 mM的乙醇浓度与人和动物的行为效应相当，它会抑制一些LC细胞的放电活动。停止乙醇灌注后，这种抑制作用很快逆转，并且每次再次给药时都能观察到。然而，如果同时灌注育亨宾（20 μM），乙醇诱导的抑制作用会迅速被拮抗。长时间洗脱育亨宾后，这种效应是可逆的。这表明α2肾上腺素能受体可能与乙醇对LC去甲肾上腺素能神经元的抑制作用有关，也许还与耐受性的发展有关。然而，也讨论了其他假说，因为育亨宾也能拮抗其他类型的受体。
