Cocaine chemogenetics blunts drug-seeking by synthetic physiology.

ABSTRACT: Chemical feedback is ubiquitous in physiology but is challenging to study without perturbing basal functions. One example is addictive drugs, which elicit a positive-feedback cycle of drug-seeking and ingestion by acting on the brain to increase dopamine signalling^1-3. However, interfering with this process by altering basal dopamine also adversely affects learning, movement, attention and wakefulness⁴. Here, inspired by physiological control systems, we developed a highly selective synthetic physiology approach to interfere with the positive-feedback cycle of addiction by installing a cocaine-dependent opposing signalling process into this body-brain signalling loop. We used protein engineering to create cocaine-gated ion channels that are selective for cocaine over

SUBMITTER: Gomez JL 

PROVIDER: S-EPMC12527922 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature