Multi-organ-on-chip device for modeling opioid reinforcement and withdrawal, and the negative affective component of pain: a therapeutic screening tool

We are developing a human iPSC-derived model of a key component of addictive circuitry – the dopaminergic and GABAergic neurons of the midbrain, recognized as responsible for mediating the reinforcing properties of many classes of abused drugs. Our goal is to produce a multi-tissue microphysiological system (MPS) that incorporates neurons, microglia, blood-brain-barrier (BBB), and liver metabolism on-a-chip components, which will be used to investigate the plasticity of dopamine neurons in response to repeated opioid exposure and withdrawal, using dopamine release as the primary output measure. Plasticity at the molecular level is being assessed by single-nuclei RNA sequencing (snRNAseq) and metabolomics analyses, through which we hope to identify novel targets for therapeutic interventions in treating opioid use disorder and the affective component of pain. These output measures will then be used to screen drug libraries for favorable activity.