The Role of Medial Prefrontal Cortex and Ventral Tegmental Areas in Withdrawal Syndrome in Morphine Addicted Male Rats

One of the problems of addiction treatment is the relapsing of withdrawal syndrome signs in the addicted person. Rewarding brain regions such as medial prefrontal cortex (mPFC) and ventral tegmental area (VTA) are involved in addiction and onset of withdrawal syndrome. This study was performed to investigate the relationship between these areas in demonstration or relief of withdrawal signs, electrical stimulation and lesion of mPFC, as well as blocking the relative receptors in the VTA.

In an experimental study, 42 male rats weighing 250-300 g were divided in 6 equal groups of control, morphine, and stimulation and lesion electrical receiver groups in mPFC region, and groups receiving the glutamate receptors antagonists by microinjection into the VTA. All of the groups, except the control group, received intraperitoneal morphine during 9 days as the protocol. Finally, on the 10th</sup> day, the symptoms of addiction in rats were evaluated.

The electrical stimulation of mPFC significantly increased cycling and scratching (P < 0.01) and bodylifting (P < 0.05) in comparison to the morphine group. Whereas the lesion of this area, and also microinjection of glutamate antagonists into the VTA caused significant decrease of all the withdrawal symptoms in rats.

Electrical stimulation of mPFC area increased the withdrawal symptoms in addicted rats, which was most likely due to increase of glutamatergic transmissions into the VTA and reinforcement of reward system; while destruction of this area and blocking of glutamate receptors, probably via decreasing of glutamatergic transmissions, caused decrease of morphine addiction.