Abstract:

Objective To investigate the effects of the subchronic injection of dizocilpine (MK-801) during adolescence on prepulse inhibition (PPI) and glucose tolerance of mice in adulthood. Methods Twenty mice in adolescence were randomly divided into the control group (n=10) and model group (n=10). After birth for 30-43 d, mice of two groups were injected with saline of 0.9% (4 mL/kg) and MK-801 (0.6 mg/kg) respectively once a day for two weeks. Food intake and body weight were measured each week. Open field test, PPI test, and glucose tolerance test (GTT) were performed in adulthood of mice (70-80 d after birth). Results The PPI of mice of the model group at prepulse of 79 dB intensity was significantly lower than that of the control group (P<0.05), suggesting that MK-801 successfully induced schizophrenia-like behavior of mice. Body weights of mice of the model group were significantly lower than those of the control group (P<0.05). Results of GTT showed that plasma glucose levels of mice of the model group were significantly higher than those of the control group at 90 min and 120 min after glucose injections (P<0.001，P<0.01), suggesting that abnormal glucose tolerance appeared in MK-801 induced schizophrenia-like mice. The differences of food intake and locomotor activities in open field tests of mice of the model group and control group were not statistically significant (P>0.05). Conclusion The subchronic injection of MK-801 during adolescence can induce the impairment of PPI and abnormal glucose tolerance of mice in adulthood.

Key words: dizocilpine, schizophrenia, prepulse inhibition, glucose tolerance