Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits.
Emily G PeckKatherine M HolleranAlyson M CurryKimberly M HolterPaige M EstaveJonathon P SensJason L LockeOlivia A OrtelliBrianna E GeorgeMonica H DawesAlyssa M WestNancy J AlexanderDrew D KiralySean P FarrisRobert W GouldBrian A McCoolSara R JonesPublished in: bioRxiv : the preprint server for biology (2024)
Synaptogyrin-3, a functionally obscure synaptic vesicle protein, interacts with vesicular monoamine and dopamine transporters, bringing together dopamine release and reuptake sites. Synaptogyrin-3 was reduced by chronic cocaine exposure in both humans and rats, and synaptogyrin-3 levels inversely correlated with motivation to take cocaine in rats. Synaptogyrin-3 overexpression in dopamine neurons reduced cocaine self-administration, decreased anxiety-like behavior, and enhanced cognitive flexibility. Overexpression also enhanced nucleus accumbens dopamine signaling and prevented cocaine-induced deficits, suggesting a putative therapeutic role for synaptogyrin-3 in cocaine use disorder.