No abstract

Background Altered redox state and developmental abnormalities in glutamatergic and GABAergic transmission during development are linked to the behavioral changes associated with schizophrenia. As an amino acid that exerts antioxidant and inhibitory actions in the brain, taurine is a potential candidate to modulate biological targets relevant to this disorder. Here, we investigated in mice and zebrafish assays whether taurine prevents the behavioral changes induced by acute administration of MK-801 (dizocilpine), a glutamate NMDA receptor antagonist. Methods C57BL/6 mice were intraperitoneally administered with saline or taurine (50, 100 and 200 mg/kg) followed by MK-801 (0.15 mg/kg). Locomotor activity, social interaction and prepulse inhibition of the acoustic startle reflex were then assessed in different sets of animals. Zebrafish were exposed to tank water or taurine (42, 150 and 400 mg/L) followed by MK-801 (5 µM); social preference and locomotor activity were evaluated in the same test. Results MK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability while increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish. Discussion Contradicting previous clinical and preclinical data, taurine did not show antipsychotic-like effects in the present study. However, it still warrants consideration as a preventive intervention in animal models of relevance to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients.

Background: Altered redox state and developmental abnormalities in glutamatergic and GABAergic transmission during development are linked to the behavioral changes associated with schizophrenia. As an amino acid that exerts antioxidant and inhibitory actions in the brain, taurine is a potential candidate to modulate biological targets relevant to this disorder. Here, we investigated in mice and zebrafish assays whether taurine prevents the behavioral changes induced by acute administration of MK-801 (dizocilpine), a glutamate NMDA receptor antagonist. Methods: C57BL/6 mice were intraperitoneally administered with saline or taurine (50, 100 and 200 mg/kg) followed by MK-801 (0.15 mg/kg). Locomotor activity, social interaction and prepulse inhibition of the acoustic startle reflex were then assessed in different sets of animals. Zebrafish were exposed to tank water or taurine (42, 150 and 400 mg/L) followed by MK-801 (5 uM); social interaction and locomotor activity were evaluated in the same test. Results: MK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability while increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish. Discussion: Contradicting previous clinical and preclinical data, taurine did not show antipsychotic-like effects in the present study. However, it still warrants consideration as a preventive intervention in animal models of relevance to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients.

Background Cognitive and negative symptoms are the core reason for the functional deficits experienced by patients with schizophrenia. Drugs that can modulate these symptoms are especially needed since no progress has been achieved in the last few decades with currently available antipsychotics. Taurine is an amino acid not used for protein synthesis but widely distributed in mammalian tissues. In the central nervous system, it has been shown to act as an inhibitory neuromodulator and possess neuroprotective, antioxidant and immunomodulatory properties. Decreased plasma and brain levels of taurine have been reported in patients as well as in animal models of schizophrenia. Furthermore, taurine improved symptoms and was well tolerated in a clinical trial of patients with first-episode psychosis. We investigated whether taurine counteracts social deficits in a zebrafish model of social interaction following acute exposure to MK-801 (dizocilpine), an NDMA antagonist commonly used in schizophrenia animal models. Methods Ninety-six 3-month-old wild-type zebrafish (Danio rerio, 50:50 male:female ratio) were used. For the social interaction test, animals were individually placed in a beaker with 200 mL of tank water (control) or taurine solution (42, 150 and 400 mg/L) for 20 minutes, and then exposed to water or MK-801 (5 µM) for another 20 minutes (n = 12 animals per group). Immediately after the treatments, zebrafish were transferred to the social interaction apparatus, a tank virtually divided in 3 vertical zones and sided by an empty tank and a tank containing 10 zebrafish. Behavior was recorded for 7 minutes and the last 5 were analyzed by automated tracking with the software ANY-Maze. The time spent in the stimulus zone was measured as a proxy for social interaction; total distance traveled was also computed. Data were analyzed by two-way ANOVA. Results MK-801 increased the total distance traveled (F1,88 = 4.935, p = 0.0289) and reduced the time spent in the tank zone next to the conspecifics (F1,88 = 23.14, p < 0.0001). No main effects of taurine or interaction effects were observed on locomotor or social interaction parameters. Discussion Although taurine has been shown to increase social interaction in rats and modulate shoaling behavior in ethanol-exposed zebrafish, it had not been tested against social deficits induced by NMDA antagonists. We observed that taurine did not counteract the hyperlocomotion and social deficit induced by acute exposure to MK-801 in zebrafish. As schizophrenia etiology has been linked to cortical and hippocampal disruption in GABAergic signaling, taurine may be effective as a preventive treatment in early neurodevelopmental stages. Further testing using animal models that more closely resemble the course of schizophrenia are thus needed to investigate the potential of this molecule.