Biomaterial Database

Cocaine-induced locomotor stimulation involves autophagic degradation of the dopamine transporter. 2021

Maged M Harraz, and Prasun Guha, and In Guk Kang, and Evan R Semenza, and Adarsha P Malla, and Young Jun Song, and Luke Reilly, and Isaac Treisman, and Pedro Cortés, and Mark A Coggiano, and Vijayabhaskar Veeravalli, and Rana Rais, and Gianluigi Tanda, and Solomon H Snyder

The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.

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.

UI	MeSH Term	Description	Entries
D009714	Nucleus Accumbens	Collection of pleomorphic cells in the caudal part of the anterior horn of the LATERAL VENTRICLE, in the region of the OLFACTORY TUBERCLE, lying between the head of the CAUDATE NUCLEUS and the ANTERIOR PERFORATED SUBSTANCE. It is part of the so-called VENTRAL STRIATUM, a composite structure considered part of the BASAL GANGLIA.	Accumbens Nucleus,Nucleus Accumbens Septi,Accumbens Septi, Nucleus,Accumbens Septus, Nucleus,Accumbens, Nucleus,Nucleus Accumbens Septus,Nucleus, Accumbens,Septi, Nucleus Accumbens,Septus, Nucleus Accumbens
D003042	Cocaine	An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.	Cocaine HCl,Cocaine Hydrochloride,HCl, Cocaine,Hydrochloride, Cocaine
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D001343	Autophagy	The segregation and degradation of various cytoplasmic constituents via engulfment by MULTIVESICULAR BODIES; VACUOLES; or AUTOPHAGOSOMES and their digestion by LYSOSOMES. It plays an important role in BIOLOGICAL METAMORPHOSIS and in the removal of bone by OSTEOCLASTS. Defective autophagy is associated with various diseases, including NEURODEGENERATIVE DISEASES and cancer.	Autophagocytosis,ER-Phagy,Lipophagy,Nucleophagy,Reticulophagy,Ribophagy,Autophagy, Cellular,Cellular Autophagy,ER Phagy
D050483	Dopamine Plasma Membrane Transport Proteins	Sodium chloride-dependent neurotransmitter symporters located primarily on the PLASMA MEMBRANE of dopaminergic neurons. They remove DOPAMINE from the EXTRACELLULAR SPACE by high affinity reuptake into PRESYNAPTIC TERMINALS and are the target of DOPAMINE UPTAKE INHIBITORS.	Dopamine Plasma Membrane Transporter Proteins,Neurotransmitter Transport Proteins, Dopamine-Specific,Neurotransmitter Transporters, Dopamine-Specific,DAT Dopamine Transporter,DAT Dopamine Transporter Proteins,Dopamine Carriers,Dopamine Transporter,Dopamine Transporter Proteins,Dopamine Uptake Complex,SLC6A3 Protein,Solute Carrier Family 6 (Neurotransmitter Transporter), Member 3 Protein,Carriers, Dopamine,Dopamine Transporter, DAT,Dopamine-Specific Neurotransmitter Transporters,Neurotransmitter Transport Proteins, Dopamine Specific,Neurotransmitter Transporters, Dopamine Specific,Protein, SLC6A3,Transporter Proteins, Dopamine,Transporter, DAT Dopamine,Transporter, Dopamine,Transporters, Dopamine-Specific Neurotransmitter
D051379	Mice	The common name for the genus Mus.	Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018765	Dopamine Uptake Inhibitors	Drugs that block the transport of DOPAMINE into axon terminals or into storage vesicles within terminals. Most of the ADRENERGIC UPTAKE INHIBITORS also inhibit dopamine uptake.	Dopamine Reuptake Inhibitors,Inhibitors, Dopamine Reuptake,Inhibitors, Dopamine Uptake,Reuptake Inhibitors, Dopamine,Uptake Inhibitors, Dopamine