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Commun Biol ; 2: 418, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31754648

RESUMEN

Alpha-synuclein (α-syn) is an abundant neuroprotein elevated in cocaine addicts, linked to drug craving, and recruited to axon terminals undergoing glutamatergic plasticity - a proposed mechanism for substance abuse. However, little is known about normal α-syn function or how it contributes to substance abuse. We show that α-syn is critical for preference of hedonic stimuli and the cognitive flexibility needed to change behavioral strategies, functions that are altered with substance abuse. Electron microscopic analysis reveals changes in α-syn targeting of ventral tegmental area axon terminals that is dependent upon the duration of cocaine exposure. The dynamic changes in presynaptic α-syn position it to control neurotransmission and fine-tune the complex afferent inputs to dopamine neurons, potentially altering functional dopamine output. Cocaine also increases postsynaptic α-syn where it is needed for normal ALIX function, multivesicular body formation, and cocaine-induced exosome release indicating potentially similar α-syn actions for vesicle release pre- and post-synaptically.


Asunto(s)
Trastornos Relacionados con Cocaína/etiología , Trastornos Relacionados con Cocaína/metabolismo , Cocaína/metabolismo , Neuronas Dopaminérgicas/metabolismo , Mesencéfalo/metabolismo , Mesencéfalo/fisiopatología , alfa-Sinucleína/metabolismo , Animales , Modelos Animales de Enfermedad , Susceptibilidad a Enfermedades , Neuronas Dopaminérgicas/ultraestructura , Espacio Extracelular/metabolismo , Inmunohistoquímica , Masculino , Ratones , Ratones Noqueados , Modelos Biológicos , Motivación , Actividad Motora , Recompensa , Transducción de Señal , alfa-Sinucleína/genética
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