Laboratório de Neurobiologia e Psicofarmacologia Experimental (PsychoLab), Departamento de Farmacologia.
Programa de Pós-Graduação em Farmacologia e Terapêutica.
Int J Neuropsychopharmacol. 2023 Feb 14;26(2):125-136. doi: 10.1093/ijnp/pyac073.
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 N-methyl-D-aspartate (NMDA) receptor antagonist.
C57BL/6 mice were i.p. 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.
MK-801 induced hyperlocomotion and disrupted sensorimotor gating in mice; in zebrafish, it reduced sociability and increased locomotion. Taurine was mostly devoid of effects and did not counteract NMDA antagonism in mice or zebrafish.
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 relevant to the prodromal phase of schizophrenia; further studies are thus necessary to evaluate whether and how taurine might benefit patients.
谷氨酸能和 GABA 能传递的氧化还原状态改变和发育异常与精神分裂症相关的行为改变有关。牛磺酸作为一种在大脑中发挥抗氧化和抑制作用的氨基酸,是调节与这种疾病相关的生物靶点的潜在候选物。在这里,我们在小鼠和斑马鱼试验中研究了牛磺酸是否能预防急性给予 MK-801(地卓西平)引起的行为改变,MK-801 是一种谷氨酸 N-甲基-D-天冬氨酸(NMDA)受体拮抗剂。
C57BL/6 小鼠经腹腔注射生理盐水或牛磺酸(50、100 和 200mg/kg),然后给予 MK-801(0.15mg/kg)。然后在不同组的动物中评估运动活动、社交互动和听觉惊跳反射的预脉冲抑制。斑马鱼暴露于水箱水或牛磺酸(42、150 和 400mg/L),然后给予 MK-801(5µM);在同一测试中评估社交偏好和运动活动。
MK-801 诱导小鼠多动和感觉运动门控障碍;在斑马鱼中,它降低了社交能力并增加了运动能力。牛磺酸大多没有作用,也不能对抗 NMDA 拮抗剂在小鼠或斑马鱼中的作用。
与先前的临床前和临床数据相矛盾,牛磺酸在本研究中没有表现出抗精神病样作用。然而,它仍然值得考虑作为精神分裂症前驱期相关动物模型的预防干预措施;因此,有必要进一步研究评估牛磺酸是否以及如何使患者受益。