Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula

Frank J Meye; Kristina Valentinova; Salvatore Lecca; Lucile Marion-Poll; Matthieu J Maroteaux; Stefano Musardo; Imane Moutkine; Fabrizio Gardoni; Richard L Huganir; François Georges; Manuel Mameli

doi:10.1038/nn.3923

Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula

Frank J Meye, Kristina Valentinova, Salvatore Lecca, Lucile Marion-Poll, Matthieu J Maroteaux, Stefano Musardo, Imane Moutkine, Fabrizio Gardoni, Richard L Huganir, François Georges, Manuel Mameli

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Addictive substances mediate positive and negative states promoting persistent drug use. However, substrates for aversive effects of drugs remain elusive. We found that, in mouse lateral habenula (LHb) neurons targeting the rostromedial tegmental nucleus, cocaine enhanced glutamatergic transmission, reduced K(+) currents and increased excitability. GluA1 trafficking in LHb was instrumental for these cocaine-evoked modifications and drug-driven aversive behaviors. Altogether, our results suggest that long-lasting adaptations in LHb shape negative symptoms after drug taking.

Original language	English
Pages (from-to)	376-8
Number of pages	3
Journal	Nature Neuroscience
Volume	18
Issue number	3
DOIs	https://doi.org/10.1038/nn.3923
Publication status	Published - Mar 2015

Keywords

Animals
Cocaine/pharmacology
Conditioning, Operant/drug effects
Dopamine Uptake Inhibitors/pharmacology
Electric Stimulation
Excitatory Postsynaptic Potentials/drug effects
Green Fluorescent Proteins/genetics
Habenula/cytology
Hindlimb Suspension
In Vitro Techniques
Luminescent Proteins/genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Motor Activity/drug effects
Mutation/genetics
Patch-Clamp Techniques
Protein Transport/drug effects
Receptors, AMPA/genetics
Swimming/psychology

Access to Document

10.1038/nn.3923

Cite this

@article{86037d4dafde41b78da6378b3af01348,

title = "Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula",

abstract = "Addictive substances mediate positive and negative states promoting persistent drug use. However, substrates for aversive effects of drugs remain elusive. We found that, in mouse lateral habenula (LHb) neurons targeting the rostromedial tegmental nucleus, cocaine enhanced glutamatergic transmission, reduced K(+) currents and increased excitability. GluA1 trafficking in LHb was instrumental for these cocaine-evoked modifications and drug-driven aversive behaviors. Altogether, our results suggest that long-lasting adaptations in LHb shape negative symptoms after drug taking. ",

keywords = "Animals, Cocaine/pharmacology, Conditioning, Operant/drug effects, Dopamine Uptake Inhibitors/pharmacology, Electric Stimulation, Excitatory Postsynaptic Potentials/drug effects, Green Fluorescent Proteins/genetics, Habenula/cytology, Hindlimb Suspension, In Vitro Techniques, Luminescent Proteins/genetics, Mice, Mice, Inbred C57BL, Mice, Transgenic, Motor Activity/drug effects, Mutation/genetics, Patch-Clamp Techniques, Protein Transport/drug effects, Receptors, AMPA/genetics, Swimming/psychology",

author = "Meye, {Frank J} and Kristina Valentinova and Salvatore Lecca and Lucile Marion-Poll and Maroteaux, {Matthieu J} and Stefano Musardo and Imane Moutkine and Fabrizio Gardoni and Huganir, {Richard L} and Fran{\c c}ois Georges and Manuel Mameli",

year = "2015",

month = mar,

doi = "10.1038/nn.3923",

language = "English",

volume = "18",

pages = "376--8",

journal = "Nature Neuroscience",

issn = "1097-6256",

publisher = "Nature Research",

number = "3",

}

TY - JOUR

T1 - Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula

AU - Meye, Frank J

AU - Valentinova, Kristina

AU - Lecca, Salvatore

AU - Marion-Poll, Lucile

AU - Maroteaux, Matthieu J

AU - Musardo, Stefano

AU - Moutkine, Imane

AU - Gardoni, Fabrizio

AU - Huganir, Richard L

AU - Georges, François

AU - Mameli, Manuel

PY - 2015/3

Y1 - 2015/3

N2 - Addictive substances mediate positive and negative states promoting persistent drug use. However, substrates for aversive effects of drugs remain elusive. We found that, in mouse lateral habenula (LHb) neurons targeting the rostromedial tegmental nucleus, cocaine enhanced glutamatergic transmission, reduced K(+) currents and increased excitability. GluA1 trafficking in LHb was instrumental for these cocaine-evoked modifications and drug-driven aversive behaviors. Altogether, our results suggest that long-lasting adaptations in LHb shape negative symptoms after drug taking.

AB - Addictive substances mediate positive and negative states promoting persistent drug use. However, substrates for aversive effects of drugs remain elusive. We found that, in mouse lateral habenula (LHb) neurons targeting the rostromedial tegmental nucleus, cocaine enhanced glutamatergic transmission, reduced K(+) currents and increased excitability. GluA1 trafficking in LHb was instrumental for these cocaine-evoked modifications and drug-driven aversive behaviors. Altogether, our results suggest that long-lasting adaptations in LHb shape negative symptoms after drug taking.

KW - Animals

KW - Cocaine/pharmacology

KW - Conditioning, Operant/drug effects

KW - Dopamine Uptake Inhibitors/pharmacology

KW - Electric Stimulation

KW - Excitatory Postsynaptic Potentials/drug effects

KW - Green Fluorescent Proteins/genetics

KW - Habenula/cytology

KW - Hindlimb Suspension

KW - In Vitro Techniques

KW - Luminescent Proteins/genetics

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Motor Activity/drug effects

KW - Mutation/genetics

KW - Patch-Clamp Techniques

KW - Protein Transport/drug effects

KW - Receptors, AMPA/genetics

KW - Swimming/psychology

U2 - 10.1038/nn.3923

DO - 10.1038/nn.3923

M3 - Article

C2 - 25643299

SN - 1097-6256

VL - 18

SP - 376

EP - 378

JO - Nature Neuroscience

JF - Nature Neuroscience

IS - 3

ER -

Cocaine-evoked negative symptoms require AMPA receptor trafficking in the lateral habenula

Abstract

Keywords

Access to Document

Fingerprint

Cite this