ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
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.
ABSTRACT
Objective To evaluate the validity and reliability of the Chinese version of Alcohol Withdrawal Scale (AWS). Methods Totally 175 patients diagnosed as alcohol dependence according to the criteria of ICD-10 were studied. Intraclass correlation coefficient (ICC) analysis was applied for examining interrater consistency and Cronbach' s α for internal consistency. Factor analysis was used to examine the construct validity. Correlation analysis between AWS and CGI,Revised Clinic Institute Alcohol Withdrawal Syndrome Scale(CIWA-Ar) were conducted to evaluate the criterion validity. Based on clinical criteria,ROC curve was calculated so as to test the discriminative ability and establish the cut-off point of the scale. Results ( 1 ) Reliability: ICC value was 0.93,and Cronbach's α was 0.83,which indicated good interrater and internal consistency. (2) Validity:the correlation coefficients of the two subscale with the total scale score were 0.78,0.83 respectively. The correlation coefficients between the subscale were 0. 81 and factor analysis revealed that each item of the scale had relatively high load on the primary factor (0.409 ～0.926). At the time of admission,the total score of the AWS was positively correlated with that of CGI ( r = 0.71, P < 0.05 ). The total score of the AWS also was positively correlated with that of CIWA-Ar ( r = 0. 86, P<0. 05). As treatment went on,total score of the AWS showed a downward trend,at the end of the first week,the total score of the AWS was positively correlated with that of CGI ( r = 0.62, P<0.05). (3)The cut-off point of AWS for mild alcohol withdrawal state was determined as ≥3. With this cut-off point,AWS had both high sensitivity (92.1% ) and specificity (73.5% ) ,and the area under curve (AUC) was 0. 91. The cut-off point of AWS for moderate withdrawal state was determined as ≥7, and the sensitivity and specificity of AWS were 94.3 % and 89.7 % respectively, with the AUC of 0.94. The cut-off point of AWS for severe withdrawal state was determined as ≥ 10. With this cut-off point AWS had both high sensitivity (94. 9% ) and high specificity (92.6% ) .with the AUC of 0.93. Conclusion AWS has good reliability and validity and can reflect the change of the disease and the efficacy of treatment.