A novel glutamatergic mechanism for the treatment of cocaine and opioid use disorders, and co-occurring anxiety
2022 Award: $39,565
Substance Use has steadily risen over the past decade and COVID-19 has exacerbated these trends. More than 50% of people diagnosed with Substance Use Disorders, are also diagnosed with co-occurring psychiatric disorders. There is a need for targeted treatments to simultaneously address these co-occurring mental health conditions. This project will systematically investigate whether a novel brain protein called TARP γ-8 could be a novel target for therapeutic interventions for substance use and anxiety.
Need/Problem: Despite tremendous need, effective pharmacotherapies for the treatment of Substance Use Disorders and co-occurring psychiatric conditions are lacking. Repeated drug use dysregulates key neurotransmitter systems in the brain and leads to enduring changes in strength and function of brain pathways that regulate reward and pleasure. It has been a historical challenge for drug development to selectively target these pathways to address co-occurring mental health conditions without undesirable side effects. This proposal offers and innovative and selective approach to targeting glutamate that may mitigate some of these side effects.
Grant Summary: Drugs like cocaine and morphine increase the strength of excitatory projections in the brain which can lead to long lasting changes in brain activity and function. I will use preclinical mouse models of cocaine and opioid use disorders, to address whether a glutamatergic protein called TARP γ-8 is a common neural mechanism of drug reward and anxiety.
Goals and Projected Outcomes: The goal of this project is to determine whether TARP γ-8 regulates the rewarding properties of cocaine and morphine. I predict that blunted drug reward and anxiety-like behavior will be seen in 1) mice lacking the gene for TARP γ-8 and 2) after administration of a novel therapeutic drug, JNJ-5, that selectively inhibits TARP γ-8.