Methamphetamine Dependence On Rat Brain Regions NT3 And Its Receptor Expression Of The Related Research

Objective:To establish a rat model of methamphetamine dependence, to detect the expression of neurotrophic factor 3(NT3), tyrosine kinase receptor C(TrkC), 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 dependent mechanism of MA were investigated. 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 was established 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 dependent periods. The methodology of in situ hybridization, western blot and quantity RT-PCR were applied to detect the expression of NT3, TrkC and p75NTR in the six different regions. Results:Compared with the control group, the CPP and scores of stereotyped behavior 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 NT3, TrkC and p75NTR had changes. In the frontal cortex, the expression of NT3 as control group and MA rely on a week, four weeks group and eight weeks group were statistically significant (P< 0.05). MA dependent 1 week.2 weeks group, and 8 weeks group have statistical significance (P < 0.05). Trk C expression, the control group and MA dependent 4 weeks groups,8 weeks group was statistically significant (P< 0.05), MA dependent one week, four weeks group and eight weeks group was statistically significant (P< 0.05). The expression of p75NTR, control group compared to MA, dependent one week group was statistically significant (P< 0.05), and the rest is compared between each group had no statistical difference. In hippocampus, the expression of Trk C, 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 NT3, the comparison between control group with 8 weeks group had statistical significance(P< 0.05). The expression of p75NTR, the comparison between 1 week group with 4 weeks group had statistical significance(P< 0.05). The expression of NT3, the comparison between control group with 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 2 weeks group,4 weeks group with 8 weeks group,2 weeks group with 8 weeks group, had statistical significance, respectively(P <0.05). In nucleus accumbens septi, the expression of Trk C, the comparison between 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 NT3, the comparison between control group with 1 week group,1 week group with 4 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). The expression of NT3, the comparison between 1 week group with 8 weeks group had statistical significance(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 the six brain regions of the same group, the expression of NT3, Trk C and p75NTR also had differences and part of them had statistical significance(P< 0.05). Conclusion:l.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. The expression of NT3, Trk C and p75NTR were different in the same cerebral region of different MA dependent group, and the expression of NT3, Trk C and p75NTR also had significant difference in the different cerebral region of same MA dependent group.3. The data indicated that the expression of NT3, Trk C and p75NTR may have an intimate correlation with the mechanism of MA dependence.