The Effects of Deep Brain Stimulation in Medial Prefrontal Cortex on Morphine Dependency and Electrical Recording of the Nucleus Accumbens

Abstract

Background: Addiction is known as a gradual process leading to the uncontrolled abuse of a substance. The main problem facing the practitioners is the high rate of return among abusers after stopping substance consumption. Deep brain stimulation (DBS) is considered as one of the methods for treating stimulant substance abuse, in which an electrical current is passed, typically at frequencies above 100 Hz, through electrodes implanted surgically in the subcortical brain nuclei. Objectives: The present study aimed to investigate the effects of high-frequency DBS (HF-DBS) applied to the medial prefrontal cortex (mPFC) on the electrical response of the accumbens nucleus as well as on the motor activity and dependency in morphine-addicted male rats. Methods: Experimental rats (n = 40) were assigned to five groups (n = 8), including saline, sham, morphine, saline+DBS, and morphine+DBS groups. The rats received DBS with a frequency of 130 Hz, amplitude of 0.2 to 0.5 mA, and repeated periods of 15 minutes with an interval of 45 minutes for 3 hours during the conditioning period in the conditioned place preference (CPP) box. Then, they were treated with saline or morphine and were subjected to stereotaxic surgery for insertion of the stimulator electrode in mPFC and the recorder electrode in AC. The electrical response of AC neurons to DBS was determined adopting the single unit recording method. Then, motor activities of different groups were assessed in order to evaluate the effects of DBS on animal movement activities. Finally, data analysis was performed using GraphPad Prism 8.1. Results: The injection of morphine enhanced the CPP score and reduced the average of spikes in the cortical neurons of the AC compared to those obtained in the sham group. These parameters were significantly decreased and increased in the animals receiving morphine+DBS compared to the morphine group, respectively. Moreover, a significant difference was observed between morphine+DBS group and morphine group in terms of the total traveled distance. Conclusions: The stimulation of the AC nucleus at high frequency reduced the addiction preference as well as enhanced the locomotor activity and primary neuron activity in the cortex of AC nucleus.