Vinpocetine halts ketamine-induced schizophrenia-like deficits in rats: impact on BDNF and GSK-3β/β-catenin pathway.

There are increasing evidences supporting the involvement of oxidative stress and neuroinflammation in schizophrenia. Vinpocetine, a nootropic phosphodiesterase-1 inhibitor, was proven to possess anti-oxidant and anti-inflammatory potentials. This research aimed to reveal the likely protective features of vinpocetine against ketamine-induced schizophrenia-like deficits in rats. Additionally, the probable mechanisms contributing to this neuroprotection were also elucidated. Vinpocetine was given (20 mg/kg, i.p.) once a day for 14 days commencing 7 days before administrating ketamine (25 mg/kg i.p.). Risperidone was applied as a reference antipsychotic. Vinpocetine pre-treatment revealed a marked amendment in the hyperlocomotion, anxiety, and short-term memory deficits induced by ketamine in rats. In rats' hippocampus, ketamine induced a drastic increase in tissue levels of dopamine, lipid peroxidation, and pro-inflammatory cytokines along with a significant decrease in glutamate, GABA, SOD, and total anti-oxidant capacity. Also, ketamine induced a reduced level of BDNF together with the potentiation of GSK-3β/β-catenin pathway that led to the destruction of β-catenin. Pre-treatment of ketamine-challenged animals with vinpocetine significantly attenuated oxidative stress, inflammation, and neurotransmitter alterations. Vinpocetine also elevated BDNF expression and prevented ketamine-induced stimulation of the GSK-3β/β-catenin signaling. This research presents enlightenments into the role of vinpocetine in schizophrenia. This role may be accomplished through its effect on oxidative stress, inflammation as well as modulating BDNF and the GSK-3β/β-catenin pathway.