PROJECT SUMMARY Despite major advances in both the preclinical and clinical addiction fields, the number of US citizens afflicted by substance use disorders (SUDs) and the lethal overdose outcomes has continuously increased over the past two decades. To tackle this alarming health issue, translational rodent models are needed to uncover the neural circuits and the cellular and molecular mechanisms underlying the development and maintenance of SUDs. In this regard, intravenous self-administration procedures is the gold standard for rodent SUD models. However, despite being one of the most reliable procedures, with clear face validity, this procedure is still limited by its tethered nature, constraining its use to restricted spaces in which rodents are exposed to unenriched environments with limited or no access food, water, or social interaction. The setting or environment is a critical component of SUD. In rodent models, evidence has shown that availability for volitional social interaction and non-social rewards such as wheel running, and operant-delivered palatable foods can decrease the consumption, the escalation, and the reinstatement in drug self-administration. Here we propose to use our complementary expertise in wireless technology, device development, and rodent models of drug abuse liability to establish wirelessly controlled intravenous self-administration experiments in complex and more ethologically- relevant environments such as enriched laboratory homecages. While wireless drug administration devices have previously been developed, they only allow for small volume and restricted number of controlled infusions. Intravenous self-administration procedures are generally composed of long-term daily session during which multiple controlled drug intakes and thus larger drug volumes are necessary to assess drug abuse liability. To tackle this limitation and permit the assessment of drug abuse liability in enriched laboratory home cages we propose to 1) develop a wireless-controlled wearable drug reservoir connected to intravenous indwelling catheter and 2) use Bluetooth mesh technology to enable homecage-based intravenous self-administration procedures using interactive connected devices. We envision that these new open-source approaches will broaden the translational value of pre-clinical SUD models by enabling new experimental designs to improve current strategies aiming at developing substance use disorders treatments.