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Objective To investigate the long-term effects of repeated neonatal administration of dizocipline maleate (MK-801),the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist,on recognition memory and hippocampal excitatory-inhibitory balance at the synaptic level in adult female rats.Methods Neonatal female Sprague-Dawley (SD) rats were randomly divided into model group and control group.Rats were administrated subcutaneously with MK-801 or normal saline from postnatal day (PND) 5 to PND14 (0.25 mg/kg,twice daily).(1) Object-in-context recognition test was performed on PND73-75.(2)The expression levels of vesicular glutamate transporter 1 (VGLUT1) and vesicular GABA transporter (VGAT) in hippocampus were detected by immunohistochemical staining.Results (1) The preference index of model group for new objects was significantly lower than that of the control group (t =-2.762,P=0.012).(2) There was no significant difference in the expression of VGLUT1 in hippocampus of MK-801 mode group(P＞0.05).Compared with control group(48.19±2.10),the VGAT level of model group in CA1 (39.60±2.19) was lower.Compared with control group (CA1:(0.99±0.05),CA3:(1.28±0.02),the ratio of VGLUT1/VGAT was significantly upregulated in CA1(1.16±0.05) and CA3(1.44±0.03) (P＜0.05).Conclusion Early NMDA receptor inhibition produces long-term deleterious effects on associative recognition memory and excitatory-inhibitory balance of hippocampus in female rats.These biochemical abnormalities may contribute to cognitive impairments observed in this study.
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Objective To investigate the effects of risperidone and its active metabolite, paliperidone (9-hydroxyrisperidone), on hyperactivity and deficient sensorimotor gating induced by MK-801 in rats. Methods Adult male Sprague-Dawley (SD) rats (n=96) were used in this study. The effects of risperidone (0.1 mg/kg) and paliperidone (0.05, 0.10 and 0.20 mg/kg) on MK-801-induced (0.40 mg/kg) hyperactivity were examined in 48 rats with with 8 animals per group.The effects of risperidone(0.5 mg/kg)and paliperidone(0.10,0.50,1.00 mg/kg)on MK-801-induced (0.25 mg/kg) deficit in prepulse inhibition (PPI) were examined in 48 rats with 8~10 animals per group. Results Risperidone (0.10 mg/kg) and paliperidone (0.05 mg/kg) diminished the MK-801-induced hyperactivity (P<0.05). But paliperidone (0.10, 0.20 mg/kg) group did not affect locomotor activity compared to the control group. Risperidone (0.10 mg/kg) and different doses of paliperidone (0.10, 0.50, 1.00 mg/kg) enhanced the PPI baseline in rats. However, only risperidone (0.10 mg/kg), but not paliperidone restored the MK-801-induced deficits in PPI. Conclusion Risperidone and paliperidone have different pharmacological actions on MK-801-induced hyperactivity and deficits in prepulse inhibition in rats, suggesting that pharmacological actions of paliperidone are different from those of risperidone, although paliperidone is the active metabolite of risperidone.
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Objective To investigate the effects of repeated neonatal administration of dizocipline maleate (MK-801), the N-methyl-D-aspartate (NMDA) receptor antagonist, on the expression of NMDA receptor subunits NMDAR 1 (NR1), NMDAR2A (NR2A), NMDAR2B (NR2B) and the protein levels of nerve growth factor (NGF) in neonatal rats. Methods Neonatal Sprague-Dawley (SD) rats were randomly divided into research group and control group, with 15 ani-mals in each group. Rats were administrated subcutaneously with MK-801 or normal saline from postnatal day (PND) 5 to PND14 (0.25 mg/kg, twice a day). The expression levels of NR1, NR2A, NR2B and NGF were examined on PND15, PND42 and PND70 in the prefrontal cortex and hippocampus. Results At PND15 (neonatal period), there were no signifi-cant differences in the expression levels of NR1, NR2A, NR2B and NGF in the prefrontal cortex and hippocampus be- tween the two groups (P>0.05). At PND42 (adolescence), NGF protein levels in the prefrontal cortex was significantly low-er in research group than in control group [(56.19±37.87) vs. (152.54±53.92), P<0.01]. At PND70 (adulthood), the expres-sion of NR1, NR2A in the hippocampus was significantly higher in research group than in control group [NR1:(149.55%± 27.00%) vs. (100.00%±32.08%);NR2A:(171.54%±19.85%) vs. (100.00%±51.04%). P<0.05]. Conclusion Neonatal re-peated treatment of MK-801 increases the expression of NMDA receptor subunits NR1, NR2A in the hippocampus in adulthood while decreases the expression of NGF in the prefrontal cortex in adolescence, suggesting that neonatal block-ade of the NMDA receptor may influence the growth and development of the nervous system.
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Objective:To evaluate the reliability and validity of the Chinese version of the Personal and Social Performance scale (PSP-CHN) in patients with schizophrenia.Methods:Totally 165 out-patients and in-patients meeting the DSM-IV-TR criteria for schizophrenia were entered in the study.Ten of subjects was included the intra-rater reliability training.The Global Assessment of Functioning Scale (GAF) was regarded as the' gold standard' to investigate the validity of PSP-CHN,and the Positive and Negative Rating Scale was used to assess the severity of disease to explore the correlative validity,in the other 155 subjects.Five to seven days after the first PSP-CHN interview,the second PSP-CHN was evaluated by another investigator to assess the test-retest reliability among 66 subjects.Twenty-seven subjects with the score of Positive and Negative Syndrome Scale (PANSS) more than 60 were followed up for 8 weeks of standardized pharmacotherapy.By the end of 8 week of treatment,the PANSS and PSP-CHN were assessed again to explore the sensitivity of PSP-CHN.Results:The internal consistency (Cronbach α=0.84) and the inter-rater reliability (κ value=0.56,ICC=0.94 for PSP-CHN total score) were good.The test-retest reliability was high [intraclass correlation coefficient (ICC) of 0.95].The scale showed good construct validity with statistically significant correlations with the Global Assessment of Functioning Scale (GAF) (ICC of 0.95).The PSP-CHN score had a good negative correlation with the PANSS total score(r=-0.79,-0.57,-0.63 and -0.71,respectively,P<0.01).After 8 week treatment,PSP-CHN total score was increased with the improvement of PANSS,and the responder showed higher increasing of PSP-CHN total score (21.2) than those partial responder(10.2),significantly.Conclusion:The Chinese version of the PSP-CHN is a convenient and valid instrument to assess the personal and social functions of stabilized and acute patients with schizophrenia.