Psychopharmacology of taurine Taurine is a ubiquitous β-amino sulfonic acid in mammals, which is involved in a variety of physiological and biological processes such as cell membrane stabilisation, osmoregulation, detoxification, immune regulation, antioxidation, and neuromodulation. It has been proposed as a cheap, safe nutraceutical that's been found to have good effect in psychiatric conditions in some studies [1,2] Taurine Taurine has been demonstrated to exert protective effects on the brain development and can improve learning ability and memory. It has also been reported that taurine could increase the emotional learning ability and memory of rats. Taurine is a psychopharmacologically active compound with potential for "a variety of therapeutic uses including as a neuro-protective, anti-cataleptic, anti-addicting, and analgesic agent." Taurine effects include: neuromodulatory, osmoregulatory, membrane stabilisation, and antioxidant action coupled with neuroprotective (taurine is a potential therapeutic agent for neurodegenerative diseases, promoting neuronal proliferation, stem cell proliferation, and differentiation, via several mechanisms), anti-diabetic (it improved glucagon activity, promoted glycemic stability, modified glucose levels, successfully addressed hyperglycemia via advanced glycation end-product control, improved insulin secretion and had a beneficial effect on insulin resistance) and anti-depressive effects (regulation of hypothalamic- pituitary-adrenal (HPA) axis and the promotion of neurogenesis, neuronal survival and growth in the hippocampus). A deficiency in taurine is related to the development of depression, suggesting a close relationship between taurine and depression. Taurine up-regulated the expression of neurotrophic factors in the hippocampus of depressive rats. The changes in the neurotransmitters of rats exposed to stress and HPA dysregulation were found to be significantly hindered by taurine administration, the effects of which were similar to the clinical antidepressants that enhance the extracelluar 5- HT and the synaptic level of these neurotransmitters in the brain [3] Supplementation of taurine could be a remedy for ADHD. Since high-dose taurine is non-toxic to humans and has been clinically used to treat various disorders, the findings in this study by using high-dose taurine (560 mg/ 100 g diet) did provide a 1 rational suggestion for high-dose taurine on ADHD treatment. Notably, much evidence indicates that taurine strengthens the effects of dopamine and has a synergistic effect with dopamine in the brain, inhibiting the reduction of sucrose consumption and improving the learning ability and spatial memory of rats that are exposed to chronic unpredictable mild stress (CUMS) [4] With regard to the dopamine elevating properties of alcohol, raised levels of taurine in the nucleus accumbens (nAc) is pivotal. Acute or chronic administration of psychotropic drug cocaine may increase extracellular release of endogenous taurine [5] Pharmacology: While acute taurine administration activates the GABAA receptor, chronic taurine feeding promotes the downregulation of the GABAA receptor (L’Amoreaux et al., 2010) and the upregulation of glutamate decarboxylase, the rate-limiting step in GABA biosynthesis (ElIdrissi and L’Amoreaux, 2008). Therefore, complex interactions within the GABAeric system, as well as in the glycine and NMDA receptors, largely define the actions of taurine in the CNS. Taurine inhibits glutamate induced Ca2+ influx through the L-, P/Q- and N-type voltage gated Ca2+ channels, as well as the NMDA receptor channel Taurine serves as an agonist of the GABAA receptor, an action that enhances chloride influx into postsynaptic neurons, which causes hyperpolarization that inhibits hyperexcitability. Suppression of kainic acid, isoniazid and picrotoxin- mediated seizures has been attributed to the actions of taurine on the GABAeric system The inhibitory neuromodulator activity of taurine also extends to the glycine receptor, as the binding of taurine to the glycine receptor evokes chloride current and suppresses neuronal firing (Wu et al., 2008). In neurodegenerative diseases, such as Alzheimer’s, Huntington’s and Parkinson’s disease, taurine cytoprotection is very promising. Taurine prevents the neurotoxicity of β-amyloid "There is reason to believe that taurine therapy should reduce the severity of Parkinson’s disease (Alkholifi et al., 2015). Indeed, it has recently been reported that reduced plasma taurine content is associated with motor severity in Parkinson’s disease (Zhang et al., 2016)." Epilepsy: Imbalances between excitatory and inhibitory neurotransmitters underlie the mechanism of seizures. Taurine is an abundant amino acid in the brain, where it serves as an inhibitory neuromodulator (Oja and Saransaari, 2013). Although taurine levels can suppress specific types of seizures, taurine deficiency is not required for 2 initiation of seizures. In animal studies, taurine administration has been found to abolish seizures evoked by a wide range of stimulants, including [D-Ala,Met ]- enkphalinamide, opioids, kainite, isoniazid, picrotoxin, penicillin and hypoxia. Nonetheless, clinical trials examining the effect of taurine treatment on human epilepsy have been mixed, with only about 1/3 of the patients responding favorably to taurine therapy (Barbeau and Donaldson, 1974; Bergamini et al., 1974; Konig et al., 1977; Rumpl et al., 1977;Mantovani and DeVivo 1979; Airaksinen et al., 1980). Fragile X syndrome is a genetic disease characterized by behavioral disorders and moderate to severe intellectual disabilities. The learning deficit (memory retention) of the fragile X mouse responds favorably to chronic oral administration of taurine (0.05% w/v) for 4 weeks, an effect seemingly linked to taurine’s GABAergic activity (Neuwirth et al., 2015). Succinic semialdehyde dehydrogenase (SSADH) deficiency is a rare autosomal genetic disease involving a key enzyme in GABA catabolism. Patients with SSADH deficiency showed symptoms such as ataxia, hypotonia, language deficits, and intellectual disability. Nearly half of the SSADH patients suffer from seizures. Because the disease is associated with disruption of GABA homeostasis, the effect of taurine therapy on symptoms of the disease before and after treatment have been examined. In a single case study of a 2-year old boy, taurine therapy (200 mg/kg/day) for 12 months improved social behavior, coordination and activity (Saronwala et al., 2008). However, in a subsequent open-label study of 18 SSADH deficient subjects administered taurine (50-200 mg/kg/day) for a period up to one year there was no major improvement in adaptive behavior with taurine (Pearl et al., 2014). [1] https://www.ncbi.nlm.nih.gov/pubmed/29561067 [2] https://www.ncbi.nlm.nih.gov/pubmed/27835719 [3] https://www.nature.com/articles/s41598-017-05051-3 [4] https://www.ncbi.nlm.nih.gov/pubmed/29694913 [5] https://www.ncbi.nlm.nih.gov/pubmed/23392920 3