Ablation of Dorsomedial Striatum Patch Compartment Results in Modification to Reward-Driven Behaviors in Rats

Abstract

The striatum is a neural structure that plays a critical role in cognitive functions, behavioral decision-making, and reward generation. The striatum exhibits a heterogeneous composition, containing neurons belonging to the patch compartment—which is thought to be involved in habitual reward-related behaviors—surrounded by neurons belonging to the matrix compartment—which is thought to be involved in adaptive motor control. Additionally, the striatum is further subdivided into the dorsolateral striatum (DLS) and the dorsomedial striatum (DMS), each with their own patch and matrix compartments. The DMS has been associated with goal-oriented behavior seen during the initial stages of addiction. Conversely, the DLS has been associated with habitual behaviors seen during late-stage addictive behaviors that are inflexible. It is thought that drug addiction is initially mediated by the DMS before DLS activity becomes predominant. Previously, it has been shown that the patch compartment of the DLS is necessary for development of habitual behavior, but the role of the patch compartment of the DMS is less clear.

Our study intends to demonstrate that selective ablation of DMS patch compartment neurons results in a significant impact on the initial development of reward-driven behaviors during the early stages of drug seeking behavior. Since patch compartment neurons express a high level of mu-opioid receptors compared to the surrounding matrix, we used dermorphin-saporin to target patch compartment neurons in the DMS and DLS for ablation. Following infusion in the DMS or DLS with dermorphin-saporin or vehicle-only infusions, rats were trained to self-administer cocaine on a progressive ratio schedule of reinforcement, starting with fixed ratio of 1 and ending with a fixed ratio of 5.

Ablation of the patch compartment of the DMS resulted in an increase in early-stage lever pressing, suggesting that the DMS patch compartment contributes to reward-driven behaviors in a way that offers support for the parallel model of DLS/DMS activity. Future studies may investigate the relationship between DMS and DLS patch/matrix compartments through measuring or inducing activity in the DMS patch while the animal undergoes behavioral training. Methods for such a study may include optogenetics, Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), or microelectrode arrays.