Abstract:

Objective: To study the effects of 5- hydroxytryptamine 2C(5-HT_2C) receptors in the lateral habenular nucleus(LHb) on anxiety behaviors in the rats with Parkinson's disease(PD),and to clarify the neural mechanisms of PD associated anxiety behaviors. Methods: A total of 126 rats were randomly divided into sham operation group (n= 63) and substantia nigrapar compacta(SNc) lesion group(n=63).The anxiety behaviors of rats in two groups such as the percentges of the time spending in center region were observed by the open field test,and the percentages of number of open arm entries and time of open arm staying were observed by elevated plus maze test;the monoamine levels in limbic related brain regions were assessed by high performance liquid chromatography with electrochemical detection;the cannula position and the degeneration of dopamine (DA) neurons after SNc lesion were confirmed by histological and immunohistochemical staining. Results: Compared with sham operation group, the percentage of time spending in center region (F_1,72 = 36.678,P<0.001),the percentage of number of open arm entries (F_1,72 = 59.077,P<0.001) and the percentage of time of open arm staying (F_1,72 = 84.245,P<0.001) of the rats in SNc lesion group were decreased.The DA levels in medial prefrontal cortex (mPFC) (P<0.01),amygdala (P<0.01),and hippocampus (P<0.05) of the rats in SNc lesion group were significantly decreased compared with sham operation group. Compared with the rats treated with vehicle in the same group, the intra-injection of 5-HT_2C receptors agonist Ro60-0175 could significantly decrease the percentages of time spending in center region(P<0.01 or P<0.01),the percentages of number of open arm entries (P<0.05 or P<0.01),and the percentages of time of open staying(P<0.05 or P<0.01) and the monoamine levels in mPFC,amygdala and hippocampus of the rats.Three monoamine levels in mPFC of the rats in two groups were decreased significantly (P<0.05 or P<0.01);in amygdala,the DA and NA levels of rats in two groups were decreased significantly (P<0.05 or P<0.01);in hippocampus,all the monoamine levels except for the NA levels of the rats in sham operation group were significantly reduced(P<0.05 or P<0.01);the behavioral test results showed that the cannula position of rats was located at 1 mm above the LHb.The immunohistochemical staining results showed that the DA neurons of the injected side of the rats in SNc lesion group were missing,and the number of DA neurons in ventral tegmetal area was lower than that in unSNc area(P<0.001). Conclusion: The anxiety-like behaviors can be induced or enhanced after activation of LHb 5-HT_2C receptors,and their mechanisms may involve the changes of monoamine levels in the related brain regions.

Key words: Parkinson's disease, anxiety, lateral habenular nucleus, 5-HT_2C receptor