Expression Of Neurotrophin 4 And Receptors In Six Cerebral Regions Related To Methamphetamine Dependent In Rats

Objective:To establish a rat model of methamphetamine dependence, to detect the expression of Neurotrophin 4(NT4) and receptors which included tyrosine kinase receptor A(TrkA), tyrosine kinase receptor B(TrkB), and p75NTR in six cerebral regions related to MA dependence, which were nucleus accumbens septi(NAc), striatum(CPu), frontal cortex(FC), hippocampus(HP), substantia nigra(SN), and ventral tegmental area(VTA). Then the neurotoxicity damages induced by MA and the dependence mechanism of MA were discussed. Methods:120 SD rats were divided into five groups which were control group,1 week group,2 weeks group,4 weeks group and 8 weeks group of MA dependence. The rat model of methamphetamine dependence was established by intraperitoneal injection of MA, after confirming the model wasestablished successfully by observing the experiment of conditioned place preference(CPP) and the stereotyped behavior(SB), the animals were injected for 1 week,2 weeks,4 weeks and 8 weeks, respectively, to establish the model of different dependence periods. The methodology of in situ hybridization, western blotting and quantity RT-PCR were applied to detect the expression of NT4, TrkA, TrkB, and p75NTR in the six different regions. Results:Compared with the control group, the scores of stereotyped behavior and CPP of four MA dependent groups had significant difference(P<0.05), that means the rat model of methamphetamine dependence was established. In the same brain regions of different dependent groups, the expression of NT4, TrkA, TrkB, and p75NTR had changes. In nucleus accumbens septi, the expression of NT4, the comparison control group with 1 week group,1 week group with 4 weeks group, and 8 weeks group,2 weeks group with 8 weeks group, had statistical significance, respectively(P< 0.05). The expression of TrkA, the comparison between 1 week group with control group, and 8 weeks group had statistical significance(P<0.05). The expression of TrkB, the comparison between control group with 1 week group, and 8 weeks group had statistical significance, respectively(P<0.05). The expression of p75NTR, the comparison between 8 weeks group with control group,1 week group, and 4 weeks group, had statistical significance, respectively(P< 0.05). In striatum, the expression of NT4, the comparison between control group with 1 week group,1 week group with 4 weeks group, and 8 weeks group,4 weeks group with 8 weeks group, had statistical significance, respectively(P＜ 0.05). The expression of p75NTR, the comparison between control group with 2 weeks group,and 8 weeks group, had statistical significance, respectively(P<0.05). The expression of TrkA, the comparison between control group with 1 weeks group,4 weeks group, and 8 weeks group,1 week group with 2 weeks group, and 8 weeks group, had statistical significance, respectively(P＜ 0.05). The expression of TrkB, the comparison between control group with 2 weeks group, and 8 weeks group,1 week group with 2 weeks group,2 weeks group with 8 weeks group, had statistical significance, respectively(P＜0.05). In frontal cortex, the comparisons between control group with 1 week group and 8 weeks group had statistical significance for the expression of NT4, respectively(P< 0.05). The expression of TrkA, the comparison between control group with 1 week group,4 weeks group, and 8 weeks group had statistical significance, respectively(P<0.05). The comparison between 1 week group with 4 weeks group, and 8 weeks group, had statistical significance, respectively(P<0.05). There were also statistical significance when comparing 2 weeks group with 4 weeks group,4 weeks group with 8 weeks group, respectively(P< 0.05). The expression of TrkB, the comparison between control group with 1 weeks group,4 weeks group, and 8 weeks group, and compared 1 week group with 2 weeks group, all had statistical significance(P<0.05). The expression of p75NTR, the comparison between control group with 1 week group had statistical significance(P<0.05). In hippocampus, the expression of NT4, the comparison between control group with 4 weeks group, and 8 weeks group,1 week group with 4 weeks group, and 8 weeks group,2 weeks group with 4 weeks group, had statistical significance, respectively(P＜ 0.05). The expression of TrkA, the comparison between 4 weeks group with 8 weeks group had statistical significance(P <0.05). The expression of TrkB, the comparison between control group with 1 week group,4 weeks group, and 8 weeks group,2 weeks group with 8 weeks group, had statistical significance(P<0.05). The expression of p75NTR, the comparison between 1 week group with 2 weeks group had statistical significance(P＜0.05). In substantia nigra, the expression of NT4, the comparison between 2 weeks group with 4 weeks group,2 weeks group with 8 weeks group, had statistical significance, respectively(P <0.05). The expression of TrkA, the comparison between control group with 2 weeks group,and 4 weeks group,1 week group with 2 weeks group, and 4 weeks group, had statistical significance, respectively(P<0.05). The expression of TrkB, the comparison between control group with 2 week group, and 4 weeks group had statistical significance, respectively(P<0.05). The expression of p75NTR, the comparison between 8 weeks group with control group, and 1 week group had statistical significance, respectively(P<0.05).In ventral tegmental area, the expression of NT4, the comparison between 2 weeks group with 4 weeks group had statistical significance(P<0.05). The expression of TrkA, the comparison between control group with 1 week group and 4 weeks group had statistical significance(P＜ 0.05). The expression of TrkB, the comparison between control group with 1 week group and 4 weeks group had statistical significance(P＜0.05). The expression of p75NTR, the comparison between control group with 1 week group, and 8 weeks group,1 week group with 4 weeks group with 8 weeks group,2 weeks group with 8 weeks group, had statistical significance, respectively(P＜0.05). In the six brain regions of the same group, the expression of NT4, TrkA, TrkB and p75NTR also had differences and part of them had statistical significance(P＜0.05). Conclusion:1.The rat model of MA dependence could be established successfully by using the method of intraperitoneal injection MA,observing the conditioned place preference(CPP) and stereotyped behavior(SB).2.Expression of NT4, TrkA, TrkB and p75NTR were different in the same cerebral region of differnent MA dependent group, and the expression of NT4, TrkA, TrkB and p75NTR also had significant difference in the different cerebral region of same MA dependent group.3. The data indicated that the expression of NT4, TrkA, TrkB and p75NTR may have an intimate corelation with the mechanism of MA dependence.