UC San Diego

Nearly 20,000 people died from cocaine overdoses in 2020 (NIDA, 2020). Similarly, overdose deaths involving opioids reached 70,000 following the pandemic (NIDA, 2021). Despite the impact that these disorders have on society, there are no FDA approved drug treatments for CUD and only three for OUD. Therefore, more effective treatment options are needed.One possible target for new pharmacotherapies is the GABA-A system. Methylglyoxal, an endogenous product, is a GABA-A agonist (Distler et al. 2012). The enzyme GLO1, metabolizes MG; thus, GLO1 inhibitors increase levels of MG. Studies have shown the co-administration of a GABA-A agonist, Midazolam, with cocaine potentiates the locomotor activation of cocaine (Morris, 2008). Similarly, co-administration of fentanyl with the GLO1 inhibitor, pBBG, increased locomotor activation (Harp et al., 2022). These studies suggest a role for GABA-A in the response to cocaine and oxycodone. This thesis investigated the potential of GLO1 to alter behavioral responses to cocaine and oxycodone, including locomotor activation and reward seeking behavior, measured by the open field test (OFT) and the conditioned place preference (CPP) test. Results showed that co-administration of pBBG with cocaine, but not oxycodone, potentiates the locomotor activation typical with cocaine. In the conditioned place preference experiments mice showed a robust CPP following conditioning trials, but preference was not affected by pBBG. Although pBBG does not affect drug seeking behavior to cocaine or oxycodone in CPP, the interaction between cocaine and pBBG supports a relationship between GABAergic signaling and the effects of cocaine.