Cocaine-induced locomotor stimulation involves autophagic degradation of the dopamine transporter.
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
06
06
2019
accepted:
01
12
2020
revised:
18
11
2020
pubmed:
9
1
2021
medline:
15
5
2021
entrez:
8
1
2021
Statut:
ppublish
Résumé
Cocaine exerts its stimulant effect by inhibiting dopamine reuptake leading to increased dopamine signaling. This action is thought to reflect binding of cocaine to the dopamine transporter (DAT) to inhibit its function. However, cocaine is a relatively weak inhibitor of DAT, and many DAT inhibitors do not share the behavioral actions of cocaine. We previously showed that toxic levels of cocaine induce autophagic neuronal cell death. Here, we show that subnanomolar concentrations of cocaine elicit neural autophagy in vitro and in vivo. Autophagy inhibitors reduce the locomotor stimulant effect of cocaine in mice. Cocaine-induced autophagy degrades transporters for dopamine but not serotonin in the nucleus accumbens. Autophagy inhibition impairs cocaine conditioned place preference in mice. Our findings indicate that autophagic degradation of DAT modulates behavioral actions of cocaine.
Identifiants
pubmed: 33414501
doi: 10.1038/s41380-020-00978-y
pii: 10.1038/s41380-020-00978-y
pmc: PMC8625012
mid: NIHMS1756646
doi:
Substances chimiques
Dopamine Plasma Membrane Transport Proteins
0
Dopamine Uptake Inhibitors
0
Cocaine
I5Y540LHVR
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
370-382Subventions
Organisme : NIDA NIH HHS
ID : P50 DA000266
Pays : United States
Organisme : NIDA NIH HHS
ID : P50 DA044123
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK054514
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DA000611
Pays : United States
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