| Objective: 1. To investigate the change of 5-HT system in ADHD rats(SHR) and its relationship with the behavior of SHR. 2. To explore the effect of glucocorticoid intervention on SHR behavior. 3. To reveal the effect of glucocorticoid intervention on the central 5-HT system of SHR and the related mechanism.Methods: 1.3 weeks old spontaneously hypertensive rats(SHR) was choosed as the ADHD model, which were divided randomly into 3 groups: GR agonist group(SHR+DEX), GR inhibitor group(SHR+RU486) and SHR control group(SHR), 15 rats in each group. 15 3-week-old WKY rats were server as the normal control group(WKY group). The rats in GR agonist group were given Dexamethasone(0.5 mg/kg.d); those in GR inhibitor group were administrated by Mifepristone(54 mg/kg.d); The rats in SHR or WKY control group rats were given saline. The injection volume in all groups was same, 1ml by intraperitoneal injection at 8:00am daily, continuely for 14 days. 2. To evaluate the level of spontaneous activity and the degree of attention deficit of rats in each group by using the opening experiment and Lat maze. All rat behavioral tests were arranged in the morning at 8:00am to 10:00am. 3. With the combination of stereotaxic techniques and micro-dialysis extraction extracellular fluid specimens were extracted in the prefrontal cortex of rats, then with the chromatography and electrochemical detection the level of 5-HT was detected in the prefrontal cortex extracellular fluid specimens of rats. 4. By immunohistochemistry, the expression of GR, 5-HT1 AR and5-HT2 AR were evaluated by the cumulative optical density value.Results: 1. The open field results showed: the number of crossing the grid in SHR rats(8.007±2.355) was increased significantly(P <0.05)than that in WKY rats(3.47±1.60), but which in SHR+DEX(54.60±12.25) was decreased significantly than that in SHR group(P < 0.05), while that in SHR+RU486(8.98 ± 9.58) group had no statistical significance comparing with SHR group(P > 0.05). 2. The Lat maze test showed: the number of upright in SHR rats(157.67 ± 33.69)showed a significant increase comparing with that in WKY rats(3.027 ± 10.63)(P < 0.05), which in SHR+DEX group(102.93 ± 19.05) showed a significant decrease and in SHR+RU486group(173.67 ± 29.59) was increased significantly comparing with that in SHR group(P < 0.05), 3. The level of 5-HT in each rat prefrontal cortex extracellular fluid: 5-HTlevels in SHR rats(16.95±5.89) showed a higher level comparing with that in WKY rats(21.25±5.05, P < 0.05). Comparing with that in SHR group, the content of 5-HT in SHR+DEX group(21.35 ± 4.08) showed a higher level(P < 0.05) and that in SHR+RU486 group(13.17 ± 2.65) showed a significant reduction(P < 0.05). 4. The expression of GR, 5-HT1 AR and 5-HT2 AR in the prefrontal cortex of rats: Both SHR prefrontal cortex GR level(23446±2123.34) and the expression of 5-HT2AR(7753.02± 1870.83) were decreased(P<0.05) than those in WKY group(30725.19 ± 1474.0,314742.76 ± 2484.88). However, the expression of 5-HT1 AR in the above two groups were increased(16950.43±1413.82 vs 14228.01±1591.10, P<0.05). The level of GR in SHR+DEX group(28355.26 ± 1527.37) and the expression of 5-HT2AR(10522.13±1668.15) were increased than those in the SHR group(P<0.05), while the expression lof 5-HT1 AR were decreased(15793.23 ± 1158.94 vs 14228.01 ± 1591.10, P<0.05).The level of GR in SHR+RU486 group(20534.78 ± 3408.74) and the expression of5-HT2AR(5620.40 ± 1876.44) were decreased(P<0.05) than those in SHR group(P<0.05), while the expression of 5-HT1 AR were increased(17927 ± 2008.27 vs 16950.43±1413.82, P<0.05). The level of GR and the expression of 5-HT1 AR was weakly negative correlation(r=-0.490, P=0.026), and The GR level was obviously positive correlation with 5-HT2AR(r=0.832, P=0.008).Conclusion: 1. In the prefrontal cortex of SHR, the 5-HT level is lower, the expression level of 5-HT1 AR is increased and the expression of 5-HT2 AR is decreased.2. Glucocorticoid administration can improve the syndrome of hyperactivity, attention deficit behavior in SHR. 3. Glucocorticoid administration can increase the level of 5-HT,GR and 5-HT2 AR and reduce the 5-HT2 AR expression in the prefrontal cortex of SHR. |
PDF Full Text Request