The effect of caffeine in a model of schizophrenia-like behavior induced by MK-801 in mice

The blockade of NMDA receptors during early developmental stages is accepted as a model for schizophrenia-like behavior. This study aimed to investigate the effects of caffeine on adult behaviors in mice subjected to tests of schizophrenia-like behaviors induced by the NMDA receptor antagonist MK-801.

MK-801 (0.25 mg/kg, twice daily, 0.1 ml/10 g body weight, intraperitoneally) was administered to Balb/c mice during PND 7-10 to establish a schizophrenia-like behavior model. In one group, caffeine (10 mg/kg, twice daily, 0.1 ml/10 g body weight, intraperitoneally) was given 30 min after MK-801 administration. In another group, MK-801 was administered 30 min after caffeine injection. At 8-10 weeks of age, behavioral tests were performed sequentially: open field test (OFT), elevated plus maze test (EPM), Morris water maze test (MWM), and social interaction test.

MK-801 administration significantly increased anxiety-like behaviors and decreased exploratory behavior in the OFT by reducing the time spent in the center, the frequency of center entries, and rearing frequency, while increasing the latency to the first center entry. In the EPM, MK-801 significantly decreased the time spent in the open arms, the frequency of open arm entries, and the head-dipping behavior of the open arm while increasing the time spent in the closed arms and the latency to the first open arm entry. In the MWM, MK-801 impaired learning and memory performance. MK-801 reduced social interaction. Caffeine reversed the anxiety, social interaction, learning, and memory impairments caused by MK-801.

MK-801 administration during the neonatal period induces schizophrenia-like behaviors in adulthood, whereas low-dose caffeine can mitigate these effects.