Peripheral electrical stimulation reversed the cell size reduction and increased BDNF level in the ventral tegmental area in chronic morphine treated rats

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 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 demonstrate for the first time that the PES could facilitate the morphological recovery of the VTA dopaminergic cells damaged by chronic morphine treatment and up-regulated 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, thus underlying the effectiveness of PES in the treatment of morphine addiction.