To giveth and taketh away : determination of taurine's protective role during ethanol withdrawal through supplementation and depletion paradigms.

Abstract

The β-amino acid taurine, whose primary physiological roles involve osmoregulation and calcium modulation, exists as one of the most concentrated amino acids in the mammalian brain. As a neuroinhibitor and neuromodulator, taurine may provide a unique therapeutic approach in reducing the aversive symptoms of ethanol withdrawal that often promote further ethanol abuse. Taurine’s properties could efficiently defend sensitive neural tissues from disturbances of osmolarity and excitability, which typically manifest during episodes of ethanol withdrawal. This investigation examined taurine’s influence on ethanol withdrawal by testing the effects of both taurine treatment and taurine depletion on withdrawal-related convulsions, as well as associated neurochemical alterations in brain tissue. Results showed that taurine, administered during ethanol withdrawal, significantly reduced overall withdrawal severity in adult male C3H/HeJ mice. Conversely, significantly reduced tissue taurine levels, achieved via the taurine uptake inhibitor guanidinoethane sulfonate (GES), exacerbated the severity of ethanol withdrawal. Analysis of extracted tissues (pituitary, supraoptic nucleus of the hypothalamus, and hippocampus) suggests that taurine’s capacity to reduce withdrawal-related convulsions may result from an attenuated release of arginine vasopressin from both the pituitary and supraoptic nucleus. During ethanol withdrawal, conditions of over-hydration can lead to lower hippocampal osmolarities, which itself can produce hyperexcitable states. By inhibiting over-activated vasopressin outflow during withdrawal, taurine seemingly prevents systemic osmotic disruptions that would otherwise disturb osmolarities within sensitive hippocampal tissues. During ethanol withdrawal, treatment with exogenous taurine provides a significant reduction in withdrawal severity and may facilitate the recovery from alcoholism. Given that the current findings also reveal that taurine depletion severely aggravates the severity of ethanol withdrawal, both behaviorally and biochemically, alcohol recovery programs should consider the potential therapeutic benefits of taurine supplementation in treatment regimens.