Correlation between bilateral lesion of anterior ventral tegmental area and depression-like behavior in rats / 西安交通大学学报(医学版)

ABSTRACT

Objective: To explore the correlation between bilateral anterior ventral tegmental area (aVTA) and depression-like behavior in rats. Methods The subjects in the study were aVTA-lesioned rats which were prepared by microinjecting 6-OHDA into their aVTA nucleus. Four weeks after the operation, all the rats were examined by behavior tests, including open-field test, sucrose preference test, and forced swimming test. We recorded and calculated the number of squares crossed, rearings, sucrose preference, immobility time. Immunohistochemistry method was used to observe the change of TH-positive neurons' number in bilateral aVTA and SNc of the 6-OHDA lesioned rats. Meanwhile, we analyzed and compared the changes of DA, 5-HT, NE levels in themPFC, LHb, STr and VHPC in the two groups of rats by high performance liquid chromatography with electrochemical detection (HPLC-ED). Results ① Bilateral aVTA lesions in the rats significantly decreased the number of squares crossed and rearings and sucrose preference, increased immobility time when compared with the sham-operated rats (P<0.001). ② In the lesioned rats, the aVTA of the bilateral injected side showed partial loss of TH-ir neurons when compared with the sham-operated rats, and the bilateral SNc in aVTA lesioned rats had a coherence of changing trend, showed a certain decrease (P<0.001). ③ Compared with sham-operated rats, bilateral aVTA 6-OHDA lesioned rats' 5-HT levels in the mPFC, STr, LHB and VHPC significantly decreased. Likewise, 6-OHDA lesioned rats' NA levels in the mPFC, striatum, and habenula vHPC significantly decreased, too(P<0.001). However, bilateral aVTA 6-OHDA lesioned rats' DA levels only in the striatum showed significantly decreased when compared to the sham-operated rats (P<0.001). Conclusion Bilateral aVTA is involved in depression-like behavior. DA neurons of the VTA and the changes of monoamine neurotransmitters of the limbic and limbic-related areas may be involved in the development of depression.