Yohimbine Can Induce Ethanol Tolerance in an in Vitro Preparation of Rat Locus Coeruleus

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Abstract
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.