Lesions of the lateral habenula produce anxiolytic effects in a rat model of Parkinson’s disease

ABSTRACT

Objective: This study was designed to investigate the effects of lateral habenula (LHb) lesion on anxiety-like behaviors in parkinsonian rats.

Methods: Anxiety-like behaviors were assessed by the open field and elevated plus maze (EPM) tests in control, medial forebrain bundle (MFB)-lesioned, MFB- and LHb-lesioned and MFB-lesioned and LHb sham-lesioned rats, respectively. The levels of extracellular dopamine (DA), serotonin (5-HT) and noradrenaline (NA) in the basolateral amygdala (BLA) were measured by in vivo microdialysis and neurochemistry.

Results: Compared to control rats, MFB lesions in rats decreased the percentage of time spent in the central area in the open field test and the percentages of open arm time and open arm entries in the EPM test, indicating the induction of anxiety-like behaviors, and this lesion also decreased the level of extracellular DA in the BLA. Further, rats in the MFB + LHb lesion group showed increased percentage of time spent in the central area and the percentages of open arm time and open arm entries compared to rats in the MFB lesion group, suggesting anxiolytic effects after lesioning the LHb. Neurochemical results found that lesions of the LHb increased the levels of extracellular DA and 5-HT in the BLA in the MFB and LHb lesion groups, whereas NA level was not altered.

Discussion: These findings suggest that depletion of DA plays an important role in anxiety-like behaviors, and lesions of the LHb produce anxiolytic responses in MFB-lesioned rats, which are related to increased levels of extracellular DA and 5-HT in the BLA.

KEYWORDS:

• Lateral habenula
• anxiety
• monoamine
• Parkinson’s disease

Acknowledgments

The authors wish to acknowledge Hui-Sheng Wang for technical support.

Disclosure of potential conflicts of interest

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (Grant No. 81771383).

Notes on contributors

Cheng Xue Du

Cheng Xue Du got his Ph.D. degree from Xi’an Jiao Tong University in 2018. He has published several papers about depression and anxiety in Parkinson’s disease (PD), and continued his research, focusing on the non-motor symptoms such as depression, anxiety and cognitive dysfunction in PD.

Yuan Guo

Yuan Guo is an associate professor in Xi’an Jiaotong University. She got her Ph.D. degree in 2009 from Xi’an Jiaotong University. She has been working in the field of neuroscience and her main research interest is the central mechanism of Parkinson’s disease in recent years. She has presided several research projects such as National Natural Science Foundation of China, China Postdoctoral Science Foundation and is also participated in more than 10 research projects. She has published 31 research papers.

Jian Liu

Jian Liu is a professor in Xi’an Jiaotong University. He got his Ph.D. degree in 1994 from Xi’an Medical University. His basic interest is in neuroscience research, currently focusing on neurobiology of Parkinson’s disease. Total international publications are more than 60. He has hosted and participated in the National Natural Science Foundation of China and other research projects.