Effects of Electrical Stimulation and Lidocaine Injection of Lateral Habenula Nucleus in the Addicted Rats with Morphine Self-administration

Abstract

Background: Addiction is one of the critical problems in public health. The lateral habenula (LHb) is a brain structure that plays an important role in sleep, reward-based decision-making, punishment avoidance, and stress. Based on the function of the LHb in addiction, this study examined the impacts of electrical stimulation (ES) and temporary inactivation of the LHb by lidocaine on the process of morphine addiction. Methods: The anesthetized animals were placed in the stereotaxic device. A cannula and electrode were inserted into the LHb for stimulation at both low and high intensities (LI: 25 and HI: 150 mu A), and injecting lidocaine, respectively. Then, jugular vein was catheterized. After recovery, an 11-day self-administration protocol was performed. Animals received morphine or saline during each session. Finally, the counts of both active and passive lever presses, along with the instances of self-infusions, were documented and assessed. Results: Morphine led to an increase in the number of active lever presses in the morphine group compared to the saline group (P < 0.001). HI-ES and lidocaine injection decreased the changes compared to the morphine group (P < 0.001). In addition, the number of infusions in the morphine group was higher than the saline group after the 6(th) day (P < 0.001); HI-ES and lidocaine injections reduced the alterations relative to the morphine group (P < 0.006, P < 0.001, respectively). Conclusion: The results indicate that HI-ES of the LHb and lidocaine injection into this region reduce morphine self-administration and active lever pressing. These findings underscore the prominent role of the LHb in regulating reward-related behaviors and drug consumption.