Synaptogyrin-3 Prevents Cocaine Addiction and Dopamine Deficits
Peck, E. G.; Holleran, K. M.; Curry, A. M.; Holter, K. M.; Estave, P.; Sens, J. P.; Locke, J.; Ortelli, O.; George, B.; Dawes, M.; West, A. M.; Alexander, N.; Kiraly, D.; Farris, S.; Gould, R. W.; McCool, B.; Jones, S. R.
Show 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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