Novel insights into the effect of paroxetine administration in pilocarpine‑induced chronic epileptic rats
- Wan‑Hui Lin
- Xiao‑Feng Li
- Ming‑Xing Lin
- Ying Zhou
- Hua‑Pin Huang
Published online on: September 28, 2017
The aim of the present study was to investigate the role of paroxetine intervention in epilepsy, and its association with the expression of serotonin transporter (SERT) and hippocampal apoptosis. Thirty adult male Sprague Dawley rats were divided into control vehicle (n=6) and epileptic (n=24) groups. Status epilepticus (SE) was induced via systemic injection of pilocarpine, and seizure activity was monitored via video electroencephalogram. The epileptic group was then randomly divided into two groups; Four weeks following SE induction, paroxetine (5 mg/kg/day; SE + paroxetine group) or normal saline (SE group) was intraperitoneally injected for 4 weeks. Brain tissue was collected to evaluate apoptosis via terminal deoxynucleotidyl transferase dUTP nick‑end labeling. SERT, B‑cell lymphoma‑2 (Bcl‑2) and brain derived neurotropic factor (BDNF) expression levels were evaluated by western blotting, and miR‑16 expression was evaluated by reverse transcription‑quantitative polymerase chain reaction. Paroxetine did not affect the mortality of the pilocarpine‑induced chronic epileptic rats. Spontaneous recurrent seizures (SSRs) were observed 7‑28 days following SE induction. The frequency and stage of the SSRs were reduced by paroxetine administration. Apoptotic cells were observed in the epileptic hippocampus. Following paroxetine intervention, the staining intensity and number of apoptotic cells were significantly decreased. Expression levels of BDNF and Bcl‑2 were lower in the SE group compared with the vehicle group. The former was not altered by paroxetine injection; however, the latter was increased. In the SE group, SERT expression was not altered in the raphe nucleus but was decreased in the hippocampus. Following paroxetine administration, SERT expression was decreased in the raphe nucleus and increased in the hippocampus. In the SE group, miR‑16 expression was decreased in the raphe nucleus and increased in the hippocampus. Following paroxetine administration, miR‑16 expression was not altered in the raphe nucleus but was reduced in the hippocampus. In conclusion, the seizures and hippocampal apoptosis observed in chronic epileptic rats were alleviated by paroxetine treatment. This effect may be associated with the reduced Bcl‑2 and BDNF expression and the modulation of SERT expression. The alterations in miR‑16 expression may provide a potential explanation for the modulation of apoptosis; however, further research is required to determine the complete underlying molecular mechanism.