Neuroprotective role of taurine on MK-801-induced memory impairment and hyperlocomotion in zebrafish

Abstract

Schizophrenia is a neuropsychiatric condition that reaches around 1% of people worldwide. Because taurine exerts a neuroprotective role in the brain, this molecule is a promising candidate to reduce schizophrenia-like symptoms. Here, we investigated a possible neuroprotective role of taurine against MK-801-induced memory deficit and hyperlocomotion in zebrafish using the inhibitory avoidance task and the novel tank diving test, respectively. First, we assessed the influence of different MK-801 doses (0.1, 0.3, 0.5, 1 and 2 mg/kg, i.p.) on memory consolidation. Although all MK-801 doses tend to reduce the retention index, only 2 mg/kg MK-801 showed robust amnesic effects. Then, we evaluated whether taurine pretreatments (42, 150 and 400 mg/L for 60 min) prevent MK-801-induced cognitive impairment. Immediately after the training, animals were exposed to non-chlorinated water or taurine and subsequently challenged with 2 mg/kg MK-801, i.p. The test session was performed 24 h after training. Although taurine alone did not change memory retention when compared with control, taurine pretreatments prevented MK-801-induced memory deficit. Importantly, no locomotor changes were observed 24 h after the training session. In the novel tank diving test, MK-801 induced hyperlocomotion and disrupted vertical activity, while 400 mg/L taurine pretreatment prevented these effects. Overall, our novel findings indicate a neuroprotective role of taurine against MK-801-induced memory deficit and hyperlocomotion, reinforcing the growing utility of zebrafish models to investigate the beneficial effects of different compounds against glutamate excitotoxicity.

Keywords: Glutamate excitotoxicity; Inhibitory avoidance task; Memory deficit; Neuroprotection; Schizophrenia; Zebrafish.