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

doi:10.1101/2024.07.27.605436

NeurosciencebioRxivJul 27, 2024

Preprint

Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits

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

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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