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[Preprint]. 2024 Aug 7:2024.07.27.605436.
doi: 10.1101/2024.07.27.605436.

Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits

Emily G Peck, Katherine M Holleran, Alyson M Curry, Kimberly M Holter, Paige M Estave, Jonathon P Sens, Jason L Locke, Olivia A Ortelli, Brianna E George, Monica H Dawes, Alyssa M West, Nancy J Alexander, Drew D Kiraly, Sean P Farris, Robert W Gould, Brian A McCool, Sara R Jones

Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits

Emily G Peck et al. bioRxiv. .

Abstract

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.

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