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

      Ahn, Jamin Paul; School of Medicine
      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.
    • Treatment of Neuropathic Pain Using 1-O-Hexyl-2,3,5- Trimethylhydroquinone (HTHQ)

      Shoaga, Elizabeth Omolara; School of Medicine
      Neuropathic pain is caused by a primary lesion or injury to the nervous system and can be spontaneous, with no obvious peripheral stimulus. Pain results from the complex interplay between signaling systems and individual perception. Neuropathic and chronic pain effect more than 100 million Americans while costing the country billions of dollars annually to treat and manage. The purpose of this research study was to discover if preemptive or post-injury treatment with 1-O-Hexyl-2,3,5- trimethylhydroquinone (HTHQ), a hydroquinone monoalkyl ether known for its antioxidative abilities, effectively alleviates neuropathic pain induced by partial sciatic nerve ligation in rats. In order to test the effectiveness of HTHQ in reducing neuropathic pain, we began by taking preliminary baseline behavior assessments to test animal pain response prior to injury. Some animals were treated with HTHQ for three consecutive days prior to the performance of partial sciatic nerve ligation (pSNL) surgery, while some were treated each day beginning four days after the induction of injury. Animal behavior was observed again for 10 days after nerve injury and drug treatment. The levels of antioxidant and pro-inflammatory proteins were analyzed using the western blot technique in order to determine the effectiveness of HTHQ at treating neuropathic pain. Preliminary findings suggests that treatment with HTHQ three days prior to nerve ligation surgery showed an increase in antioxidant catalase, an enzyme responsible for converting hydrogen peroxide to water and oxygen, in the spinal cords of injured rats compared to those that were not treated 10-days after nerve injury. Our findings also demonstrate that rats treated with HTHQ three days prior to nerve injury showed an increase in antioxidative protein SOD2 but also decreases the expression of pro-inflammatory protein IL-1ß compared to vehicle treated neuropathic rats. There were no therapeutic changes seen in rats treated with HTHQ four days after pSNL surgery.