Temporal resolution and determination of the mechanism of ethanol-induced taurine efflux

The mesocorticolimbic dopamine pathway is closely associated with the drug reward system. Drugs of abuse enhance neural transmission of this pathway and are responsible for the reinforcing properties of ethanol. The key neurotransmitter involved in this pathway and with addictive behaviors is dopamine. However, when ethanol is given intraperitoneal an increase in the efflux of taurine is observed.; Taurine is a sulphonated amino acid found in millimolar concentrations in the brain. Although taurine has many functions it is known as a major osmolyte in neuronal tissue; however it can act as an agonist at GABAA receptors and antagonist at NMDA receptors, similar to ethanol. In addition, taurine can be released in several different ways such as a typical neurotransmitter or through an osmotic channel or, in extreme conditions, the reversal of the taurine transporter. Since taurine is increased in response to ethanol in a known addiction pathway, it is necessary to understand the mechanism of this release to better ascertain the function of ethanol-induced taurine efflux.; Capillary electrophoresis with laser-induced fluorescence was used to examine ethanol-induced taurine efflux. A dose-dependent release of taurine in response to increasing cumulative dosages of ethanol was observed. The efflux of taurine was specific and larger in the nucleus accumbens compared to the striatum, while other amino acids were not affected. In addition, rats trained to self-administer ethanol displayed an increase in taurine efflux in the nucleus accumbens. To further examine the mechanism of efflux, the sodium from the artificial cerebrospinal fluid (ACSF) was reduced to induce the osmotic release of taurine. Osmotic inhibitors were tested, and 4-Acetamido-4 '-isothiocyanato-2,2'-stilbenedisulfanic acid disodium salt hydrate (SITS) was successful at blocking osmotic-induced taurine efflux. Several conditions to the ACSF were applied to block the ethanol-induced efflux of taurine by reverse dialysis. SITS and calcium-free ACSF with EGTA were successful at reducing ethanol-induced taurine efflux. The results suggested that the mechanism of ethanol-induced taurine efflux was osmotically mediated. However, local perfusion of ethanol did not induce any efflux. Instead of the local osmotic effect of ethanol, ethanol-induced taurine efflux could be due to neuronal firing in other areas of the brain that causes the osmotic release of taurine.