Effects of deep brain stimulation of the ventral capsule/ventral striatum and of the subtalamic nucleus on the performance of rats in behavioral flexibility tasks.

Abstract

Behavioral flexibility is the ability to modify behavior in response to changes in environmental contingencies and appears to be compromised in Obsessive-Compulsive Disorder (OCD). In patients with OCD, the use of deep brain stimulation (DBS) of the ventral capsule/ventral striatum (VC/VS), the main target used, and of the subthalamic nucleus (STN), seems to increase behavioral flexibility. Considering that the understanding of these effects is still limited, the present study aims to investigate the effects of DBS on behavioral flexibility and the possible neural circuits involved. In the first stage, we will conduct a study of systematic literature review in order to identify publications that report the use of DBS in rodents, in the regions of VC/VS and STN. In the second stage, in an experimental study, we will investigate the effects of DBS during two tasks that measure flexible behavior and evaluate the role of the orbitofrontal cortex and the pre-limbic cortex through the reversible inactivation of these regions. For this purpose, male Wistar rats will be used, and three experiments will be carried out: 1. Standardization of the tasks of reverse learning and set-shifting in the operant conditioning box; 2. Evaluation of the effects of the DBS of VC/VS and STN on the behaviors during the tasks; 3. Evaluation of the role of the orbitofrontal cortex and the pre-limbic cortex on the effects of VC/VS and STN DBS. It is expected that DBS will increase behavioral flexibility during the performance of tasks and that this improvement will be reversed with the inactivation of the regions of the cortex.