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Preparation of Peripheral Nerve Stimulation Electrodes for Chronic Implantation in Rats
Published on: July 14, 2020
Peripheral electrical stimulation reversed the cell size reduction and increased BDNF level in the ventral tegmental
Ning-Ning Chu1, Yan-Fang Zuo, Li Meng
1Neuroscience Research Institute, The Ministry of Education and Ministry of Public Health, Peking University, Beijing 100083, PR China.
Abstract:
Chronic morphine administration induces functional and morphological alterations in the mesolimbic dopamine system (MLDS), which is believed to be the neurobiological substrate of opiate addiction. Our previous studies have demonstrated that peripheral electrical stimulation (PES) can suppress morphine withdrawal syndrome and morphine-induced conditioned place preference (CPP) in rats. The present study was designed to investigate if PES could reverse the cell size reduction induced by chronic morphine treatment in the ventral tegmental area (VTA), which is an important area of the MLDS. Immunohistochemical observations showed that the cell size of dopaminergic neurons in the VTA reduced significantly in the chronic morphine-treated rats with a concomitant decrease in the number of BDNF-positive cells compared to the saline-treated rats. A much milder morphological change, accompanying with an increased number of BDNF-positive cells, was observed in dopaminergic neurons in the rats that received repeated 100 Hz PES after morphine withdrawal. In another experiment, enzyme-linked immunosorbent assay (ELISA) reconfirmed a significant up-regulation of BDNF protein level in the VTA in the rats received 100 Hz PES after morphine abstinence. These results indicate that PES could facilitate the morphological recovery of the VTA dopaminergic cells damaged by chronic morphine treatment and up-regulate the BDNF protein level in the VTA. Activation of endogenous BDNF by PES may play a role in the recovery of the injured dopaminergic neurons in the morphine addictive rats.
Insights
Peripheral electrical stimulation (PES) can reverse morphine-induced cell damage in the brain's dopamine system. This technique may help recover dopamine neurons affected by opiate addiction.
Area of Science:
- Neuroscience
- Neurobiology
- Addiction Research
Background:
- Chronic morphine use alters the mesolimbic dopamine system (MLDS), a key area in opiate addiction.
- Morphine administration leads to reduced cell size in ventral tegmental area (VTA) dopaminergic neurons and decreased BDNF levels.
- Peripheral electrical stimulation (PES) has previously shown potential in suppressing morphine withdrawal and conditioned place preference.
Purpose of the Study:
- To investigate if PES can reverse morphine-induced cell size reduction in VTA dopaminergic neurons.
- To determine the effect of PES on BDNF levels in the VTA of morphine-treated rats.
Main Methods:
- Immunohistochemistry was used to observe VTA dopaminergic neuron cell size and BDNF-positive cells.
- Enzyme-linked immunosorbent assay (ELISA) was employed to quantify BDNF protein levels in the VTA.
- Rats were administered chronic morphine, followed by withdrawal and subsequent PES treatment.
Main Results:
- Chronic morphine treatment significantly reduced VTA dopaminergic neuron size and decreased BDNF-positive cells.
- PES treatment after morphine withdrawal resulted in milder morphological changes and an increased number of BDNF-positive cells.
- ELISA confirmed a significant up-regulation of BDNF protein in the VTA following PES treatment.
Conclusions:
- PES can facilitate the morphological recovery of VTA dopaminergic neurons damaged by chronic morphine.
- PES up-regulates BDNF protein levels in the VTA, suggesting a role in neuronal repair.
- Activation of endogenous BDNF by PES may be crucial for recovering injured dopaminergic neurons in morphine addiction.

