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Objective Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that is caused predominantly by the degeneration of the nigrostriatal dopaminergic pathway. Lateral habenula (LHb) has efferent projections that terminate in the substantia nigra pars compacta (SNpc) and electrical stimulation of the LHb effectively suppresses the activity of dopamine-containing neurons in the SNpc. This study was aimed to investigate whether LHb lesions can ameliorate the syndromes of PD via affecting the activities of SNpc neurons in 6-hydroxydopamine (6-OHDA)-induced PD model rats. Methods Concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, which is the area projected by the SNpc dopaminergic neurons were assayed by high-performance liquid chromatography (HPLC) coupled with fluorescence detection. The immunohistochemical method was applied to detect the numbers of tyrosine hydroxylase (TH)-positive cells in the substantia nigra. Results The results showed that LHb lesions induced a significant reduction in apomorphine-induced rotational behavior. The DA, DOPAC and HVA levels in the striatum of PD model rats were increased by the LHb lesions. Conclusion Therefore, we speculate that the LHb lesions induced a significant amelioration in motor disorders via increasing the DA levels in the striatum, which may lead to a potential therapeutic strategy for the treatment of PD.

Substance P (SP) levels are closely related with the pathogenesis of depression. Recent work has focused on antidepressive effect of substance P receptor antagonist (SPA), however, its action site and mechanism remain largely unresolved. Our previous results showed that the lateral habenula (LHb) plays a key role in the pathogenesis of depression. The current study investigated the effects of SPA microinjected into LHb on the behavioral responses of two rat models that exhibit depression-like behavior. To produce adult rats that exhibit depression-like behavior, rats were either exposed to chronic mild stress (CMS), or chronically administered clomipramine (CLI), a tricyclic antidepressant, during the neonatal state of life. The forced-swimming test (FST) was used to evaluate behavioral responses. Furthermore, we measured serotonin (5-HT) levels in dorsal raphe nucleus (DRN) using microdialysis. The FST showed a decreased immobility time and an increased climbing time after SPA injection into the LHb of depression-like behavior rats. In addition, 5-HT levels in DRN increased after SPA was microinjected into LHb of the rats that exhibited depression-like behavior. This study demonstrates that LHb mediates antidepressive effect of SPA by increasing 5-HT levels in the DRN, suggesting that the LHb may be a potential target of antidepressant.

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