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

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.