Maslinic acid ameliorates NMDA receptor blockade-induced schizophrenia-like behaviors in mice

Schizophrenia is a chronic psychotic disorder related to hypo-functioning of glutamatergic neurotransmission and characterized by positive, negative, and cognitive symptoms [1]. Major treatments for schizophrenia relieve the positive symptoms but do not react with negative or cognitive symptoms. Maslinic acid is contained in Syzygium aromaticum (clove) and it has been reported to have protective effects in the liver and anti-tumor effects [2, 3]. Here, we investigated whether maslinic acid modulates the schizophrenia-like behaviors in mice elicited by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist. A single administration of maslinic acid blocked the MK-801-induced hyperlocomotion, not the normal naïve mice in open field test [4]. In the acoustic startle response test, maslinic acid did not have any effects on the acoustic startle response or prepulse inhibition (PPI) level, however, reversed the MK-801-induced PPI deficit in mice. In the social novelty preference test, maslinic acid ameliorated the deficit of social behaviors induced by MK-801. In the novel object recognition test, the attention and recognition memory impairments induced by MK-801 were restored by a single administration of maslinic acid. Additionally, maslinic acid normalized the MK-801-induced alterations of signaling molecules including phosphorylation levels of GSK-3β, CREB and ERK in the prefrontal cortex [5, 6]. Overall, maslinic acid reversed the schizophrenic symptoms induced by MK-801, and these effects may be partly mediated through GSK-3β, CREB and ERK activation. These findings suggest that maslinic acid could be a candidate for the treatment of several symptoms of schizophrenia, including positive symptoms, sensorimotor gating disruption, social interaction deficit and cognitive impairments.

Keywords: Maslinic acid, Schizophrenia-like behavior, cognition, prepulse inhibition.

References:

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