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The neuropharmacology of taurine

Taurine is a highly abundant “amino acid” in the brain. Although the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action. In this context, we also highlight how zebrafish models of brain disorders may present interesting approaches to assess molecular mechanisms underlying positive effects of taurine in the brain. Finally, we outline recent advances in zebrafish drug screening that significantly improve neuropsychiatric translational research and small molecule screens.

Taurine is a highly abundant “amino acid” in the brain. Despite the potential neuroactive role of taurine in vertebrates has long been recognized, the underlying molecular mechanisms related to its pleiotropic effects in the brain remain poorly understood. Due to the genetic tractability, rich behavioral repertoire, neurochemical conservation, and small size, the zebrafish (Danio rerio) has emerged as a powerful candidate for neuropsychopharmacology investigation and in vivo drug screening. Here, we summarize the main physiological roles of taurine in mammals, including neuromodulation, osmoregulation, membrane stabilization, and antioxidant action. In this context, we also highlight how zebrafish models of brain disorders may present interesting approaches to assess molecular mechanisms underlying positive effects of taurine in the brain. Finally, we outline recent advances in zebrafish drug screening that significantly improve neuropsychiatric translational researches and small molecule screens.

Dysfunction of excitatory and inhibitory neurotransmitters or neuromodulators is thought to underlie epileptic symptoms. Taurine, 2-aminoethanesulfonate, is a ubiquitous free amino acid abounding in the brain of humans and most animal species. It hyperpolarizes neurons and inhibits their firing. It may be a participating factor in certain subpopulations of epilepsy patients but its deficiency is not a universal prerequisite for seizures. Here, the participation of taurine in animal seizure models and human epilepsy patients is reviewed.

Taurine is an abundant amino acid in the brain that shares pharmacological effects and similar potency with ethanol. Recently, taurine-containing beverages have been reported to enhance the euphoric effects of ethanol, though the extent of this effect and the role of taurine remain speculative. The present study was designed to explore interactions between taurine and ethanol on several behaviors including locomotion, ataxia, and loss of righting. Two strains of mice, C57BL/6J and DBA/2J mice, were used to examine potential strain differences. In the first experiment, effects of various doses of taurine (0.3–3.0 g/kg), ethanol (1.0–4.2 g/kg), or taurine in combination with ethanol were assessed in a within-subjects design. Although taurine did not appear to alter effects of ethanol on any measure in either strain, the development of tolerance to locomotor effects and sensitization to ataxic effects of ethanol in DBA/2J mice complicated interpretation of these results. In a second experiment, drug-naïve mice were assigned to one of four treatment groups: saline + saline, saline + ethanol (1.78 g/kg), taurine (1.78 g/kg) + saline, or ethanol + taurine. In this experiment, taurine pretreatment significantly attenuated the locomotor-stimulating effect of ethanol in both strains (but to a greater extent in C57BL/6J mice) and appeared to reduce the ataxic effects of ethanol in C57BL/6J mice. In conclusion, the interaction between taurine and ethanol is subtle. Further, results are inconsistent with the notion that taurine plays a major role in the locomotor, ataxic, or loss of righting effects of ethanol.

The effects of taurine supplementation on visual discrimination in mice were examined. Taurine, 2-aminoethane-sulphonic acid, found in high concentrations in the central nervous system of mammals and in human milk, has been shown to be essential for development. Male mice were divided into four groups according to taurine supplementation periods. 1) Lifelong: taurine (400 mg/kg/day) was dissolved in distilled water and provided as drinking water. In the prenatal period, taurine was given via the mother. After weaning mice were administered taurine in drinking water. 2) Pre-weaning: mice were exposed to taurine prior to weaning, 3) Post-weaning: mice were exposed to taurine after weaning. 4) Control: no supplementation of taurine. It was shown that the Lifelong group required a longer period of time to acquire visual discrimination than the Control group. Conversely, in the Post-weaning group, mice learned the task faster than Controls. Visual discrimination learning time in the Pre-weaning group showed no significant difference compared with that in the Control group. From these results, we suggest that the perinatal to early postnatal period is a “sensitive period” where taurine supplementation can result in retardation of learning in later life. At the same time, taurine supplementation after weaning improved visual discrimination learning. Thus, timing of taurine supplementation affected learning.

The effects of taurine, an inhibitory amino acid, on the behavior of male mice were examined in the elevated plus-maze test of anxiety. Acute taurine treatment (60 mg/kg, PO) significantly increased the percentage of time spent in the open arms. Moreover, when taurine was administered daily for seven days and the plus-maze test was conducted 40 minutes after the last administration, a significant increase of the percentage of time in the open arms was observed even at dose of 2.5 mg/kg, however the open arm entries and the total entries were unaffected at any dose tested. In order to get a comprehensive profile of drug action, detailed behavioral analyses were further exerted. Single administration of 60 mg/kg taurine can significantly reduce the total rears. The results suggest that taurine have some anxiolytic-like properties, although its effects seem more limited and are not consistent with those presented by classic anxiolytics, such as diazepam.