| Tourette Syndrome(TS)is a neuro developmental disorder of childhood onset characterized by chronic motor and vocal tics.The incidence of TS in boys is higher.Anti-androgen therapy can reduce the tic symptoms of TS patients.The function of dopaminergic nervous system in TS patients was enhanced.Based on the above,it is presumed that the dysfunction of dopamine(DA)neurological is associated with disorder of androgen levels.In our studies,we establish the animal model of high testosterone levels in Wistar rats by subcutaneous injection of testosterone propionate(TP).The contents of DA,DOPAC(3,4-Dihydroxyphenylacetic acid)and HVA(4-Hydroxy-3-methoxyphenylacetic acid)were measured by liquid chromatography-tandem mass spectrometry(LC-MS/MS).The effects of androgen treatment on the functional activities of DA neurons were observed.In addition,the effects of the parameters of open field were observed in the early TP treated rats which injected by dopamine D2 receptor antagonist-haloperidol(Hal)inhibited dopaminergic neurons in adolescence(7-week).The purposes were exploring the improvement effects on the open field behavior and the possible mechanism in dopamine D2 receptor antagonist treated early TP administrated rats.Part one Effects of testosterone propionate on early functional activities of dopamine neurons in ratsObjective: To observe the changes of DA and its metabolites in the caudate putamen and nucleus accumbens of TP early treated rats,and to explore whether TP involved in the DA signal transmission changes.Methods:28 male rats were randomly divided into two groups: 3-week(3W)group and 7-week(7W)group.Rats in each age group were divided into 2 subgroups(Con group and TP group)and 7 rats per subgroup.Two TP subgroups rats were injected subcutaneously with TP at a dose of 0.5 mg/per rat,once a day for 14 days.Two Consub groups rats were given equal volume of sesame oil respectively.The rats were sacrificed at 3 weeks and 7 weeks of age respectively.The contents of DA,DOPAC and HVA in the caudate putamen and nucleus accumbens were detected by LC-MS/MS.Results:1 The contents of DA,DOPAC and HVA in the caudate putamen and nucleus accumbens of the TP-3W subgroup rats showed a significant increase compared with the Con-3W subgroup.2 The contents of DA,DOPAC and HVA in the caudate putamen and nucleus accumbens of TP-7W subgroup rats showed a significant increase compared with the Con-3W subgroup.Summary:TP increased the contents of DA and its metabolites in the caudate putamen and nucleus accumbens,suggesting that TP enhanced the functional regulation of dopaminergic neurons in the caudate putamen and nucleus accumbens.Part two: Improvement effects of Hal on open field behavioral deficits in the early testosterone propionate treated ratsObjective: To investigate the improvement effects of Hal on the open field behavior deficits in the early TP treated ratsMethods:42 male rats were randomly divided into Con group,TP group,Con+0.02 Hal group,Con+0.15 Hal group,TP+0.02 Hal group and TP+0.15 Hal group.TP group,TP+0.02 Hal group and TP+0.15 Hal group rats were injected subcutaneously with TP on the 7th day after birth.The dose was 0.5 mg/per rat,once every day for 14 days.Con group,Con+0.02 Hal group,Con+0.15 Hal group rats were given equal volume of sesame oil.The rats were reared to 49days(7-week),and then the open field experiment was carry out.The rats in Con+0.02 Hal group,Con+0.15 Hal group,TP+0.02 Hal group and TP+0.15 Halgroup rats were injected intraperitoneally of Hal at 1 hour before the open field experiment.Con group and TP group were injected with normal saline.The differences between the experimental rats were observed by the open field behavior indicators.Results:1 Immobile-sniffingCompared with Con group,the number of immobile-sniffing did no significantly change in Con+0.02 Hal and TP+0.15 Hal groups,decreased by52% in Con+0.15 Hal group(P < 0.01),increased by 60% in TP group(P <0.01),increased by 39% in TP+0.02 Hal group(P < 0.01).Compared with TP group,the number of immobile-sniffing did no significant change in TP+0.02 Hal group,decreased by 35% in TP+0.15 Hal group(P < 0.01).2 Exploratory behaviorsCompared with Con group,the number of walking did no significantly change in the Con+0.02 Hal and TP+0.15 Halgroups,while decreased by 51%in Con+0.15 Hal group(P < 0.05),increased by 87% in TP group(P < 0.05),has doubled(P < 0.01)in TP+0.02 Hal group.Compared with TP group,the number of walking in TP+0.02 Hal group had no significant change,and decreased by 54% in TP + 0.15 Hal group(P < 0.01).Compared with Con group,the number of climbing did no significantly change in the Con+0.02 Hal,TP+0.02 Hal and TP+0.15 Hal groups,and decreased by 54% in Con+0.15 Hal group(P < 0.05),increased by 72% in TP group(P < 0.05).Compared with TP group,the number of climbing in TP+0.02 Hal group decreased by 16%(P < 0.01),decreased by 61% in TP+0.15 Hal group(P < 0.05).Compared with Con group,the number of rearing did no significantly change in the Con+0.02 Hal,TP+0.02 Hal and TP+0.15 Hal groups,while decreased by 71% in Con+0.15 Hal group(P < 0.05),increased by 58% in TP group(P < 0.05).Compared with TP group,the number of rearing did no significant change in TP+0.02 Hal group,and decreased by 53% in TP+0.15 Hal group(P < 0.05).Compared with Con group,the number of sniffing did no significantly change in the Con+0.02 Hal and TP+0.15 Hal groups,while decreased by 56%in Con+0.15 Hal group(P < 0.05),increased by 75% in TP group(P < 0.01),increased by 62% in TP+0.02 Hal group(P < 0.01).Compared with TP group,the number of sniffing did no significant changes in TP+0.02 Hal group,and decreased by 57% in TP+0.15 Hal group(P < 0.05).3 Motor behaviorsCompared with Con group,the vertical exercise value did no significantly change in Con+0.02 Hal,TP+0.02 Hal and TP+0.15 Hal groups,and decreased by 60% in Con+0.15 Hal group(P < 0.01),increased by 67% in TP group(P < 0.05).Compared with TP group,the vertical exercise value did not significant change in TP+0.02 Hal group,and decreased by 58% in TP+0.15 Hal group(P < 0.01).Compared with Con group,the horizontal exercise value did no significantly change in Con+0.02 Hal and TP+0.15 Hal groups,while decreased by 53% in Con+0.15 Hal group(P < 0.01),has doubled in TP group(P < 0.01),increased by 62% in TP+0.02 Hal group(P < 0.01).Compared with TP group,the horizontal exercise value was decreased by 27% in TP+0.02 Hal group(P <0.01),and decreased by59% in TP+0.15 Hal group(P < 0.01).Compared with Con group,the total length did no significantly change in Con+0.02 Hal and TP+0.15 Hal groups,and decreased by 63%(P < 0.01)in Con + 0.15 Hal group,has doubled in TP group(P < 0.01),increased by 61%(P < 0.01)in TP + 0.02 Hal group.Compared with TP group,the total length decreased by 28% in TP+0.02 Hal group(P < 0.01),decreased by 60% in TP+0.15 Hal group(P < 0.01).4 Grooming behaviorsCompared with Con group,there did no significantly change in the latency of the treatments in Con+0.02 Hal group,Con+0.15 Hal group,TP group,TP+0.02 Hal group and TP+0.15 Hal group.Compared with TP group,there did no significantly change in the latency of TP+0.02 Hal and TP+0.15 Hal groups.Compared with Con group,there did no significantly change in the number of grooming in Con+0.02 Hal,Con+0.15 Hal,TP+0.02 Hal and TP+0.15 Hal groups,increased by 63% in TP group(P < 0.01).Compared with TP group,the number of grooming of TP+0.02 Hal group did no significantly change,decreased by 37% in TP+0.15 Hal group(P < 0.05).Compared with Con group,the duration of grooming did no significantly change in Con+0.02 Hal,TP,TP+0.02 Hal and TP+0.15 Hal groups,while decreased by 63% in Con+0.15 Hal group(P < 0.01).Compared with TP group,the duration of grooming did no significantly change in TP+0.02 Hal group,decreased by 42% in TP+0.15 Hal group(P < 0.05).Summary:1 TP early treatment resulted in the defects of open field behavior in adolescent rats.2 Dopamine D2 receptor antagonist-haloperidol significantly improved the open field defects of the TP early treated rats.It suggested that the behavioral changes of early androgen treatment associated with the enhancement of brain dopamine system.Conclusion:1 Early treatment of TP enhanced dopamine function activity of adolescent rats.2 Early treatment of TP leaded to open field behavior defects of adolescent rats.3 The behavioral changes of androgen early treatment were related to the enhancement of dopamine system in the brain.4 Dopamine D2 receptor antagonist significantly improved the open field defects of the TP early treated rats. |
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