The effects of bilateral, continuous, and chronic Deep Brain Stimulation of the medial forebrain bundle in a rodent model of depression

Abstract

BackgroundClinical trials of supra-lateral medial forebrain bundle (MFB) Deep Brain Stimulation (DBS) in treatment resistant major depressive patients have shown rapid and long-term benefits. Objective/hypothesisThe study used Flinders Sensitive Line (FSL) rats with previously identified depressive-like phenotype to assess the range of behavior modification achieved by MFB DBS. MethodsMale FSL and wild-type Sprague-Dawley rats as Controls were tested on mood/anxiety/exploration, cognitive and motor behaviors. The animals were implanted with bipolar stimulation electrodes in the MFB, and recovery was followed by 10 days of bilateral, chronic and continuous stimulation. ResultsWeight dynamics was assessed continuously and indicated similar growth rates although the FSL rats weighed approximately 20–25% less. MFB DBS had no impact on ultrasound calls emitted and the FSL rats continued to vocalize significantly less in the positive affect frequency compared to controls. Similarly, stimulation did not influence the FSL's exploration level (Elevated Plus Maze), nor locomotion (Open Field), although it reduced their freezing behavior (Open Field). Importantly, MFB DBS improved cognitive performance (Double-H) compared to Controls by reducing the time required and the number of errors committed to complete a spatial task. ConclusionMFB DBS in the FSL animals selectively affected certain types of behaviors. Exploration and vocalization remained unaltered, but cognitive performance such as speed and precision of memory recall improved compared to unstimulated and stimulated controls. Future studies should focus on the mechanisms of action of MFB DBS, and in particular on the role of dopamine in the stimulation-dependent phenotype changes.