Parkin regulates drug-taking behavior in rat model of methamphetamine use disorder

There is no FDA-approved medication for methamphetamine (METH) use disorder. New therapeutic approaches are needed, especially for people who use METH heavily and are at high risk for overdose. This study used genetically engineered rats to evaluate PARKIN as a potential target for METH use disorder. PARKIN knockout, PARKIN-overexpressing, and wild-type young adult male Long Evans rats were trained to self-administer high doses of METH using an extended-access METH self-administration paradigm. Reinforcing/rewarding properties of METH were assessed by quantifying drug-taking behavior and time spent in a METH-paired environment. PARKIN knockout rats self-administered more METH and spent more time in the METH-paired environment than wild-type rats. Wild-type rats overexpressing PARKIN self-administered less METH and spent less time in the METH-paired environment. PARKIN knockout rats overexpressing PARKIN self-administered less METH during the first half of drug self-administration days than PARKIN-deficient rats. The results indicate that rats with PARKIN excess or PARKIN deficit are useful models for studying neural substrates underlying resilience or vulnerability to METH use disorder and identify PARKIN as a novel potential drug target to treat heavy use of METH.

Automated summary

The study found that rats overexpressing PARKIN gene have stronger self-administration ability for METH, while rats with PARKIN knockout are more prone to self-administer METH. This result provides useful models for studying the neural substrates underlying resilience or vulnerability to METH use disorder and identifies PARKIN as a novel potential drug target for treating heavy use of METH.