The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.

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State: Public
Version: Final published version
Serval ID
serval:BIB_A7353BF80F5C
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
The absence of VGLUT3 predisposes to cocaine abuse by increasing dopamine and glutamate signaling in the nucleus accumbens.
Journal
Molecular Psychiatry
Author(s)
Sakae D.Y., Marti F., Lecca S., Vorspan F., Martín-García E., Morel L.J., Henrion A., Gutiérrez-Cuesta J., Besnard A., Heck N., Herzog E., Bolte S., Prado V.F., Prado M.A., Bellivier F., Eap C.B., Crettol S., Vanhoutte P., Caboche J., Gratton A., Moquin L., Giros B., Maldonado R., Daumas S., Mameli M., Jamain S., El Mestikawy S.
ISSN
1476-5578 (Electronic)
ISSN-L
1359-4184
Publication state
Published
Issued date
2015
Peer-reviewed
Oui
Volume
20
Number
11
Pages
1448-1459
Language
english
Notes
Publication types: Journal ArticlePublication Status: ppublish
Abstract
Tonically active cholinergic interneurons (TANs) from the nucleus accumbens (NAc) are centrally involved in reward behavior. TANs express a vesicular glutamate transporter referred to as VGLUT3 and thus use both acetylcholine and glutamate as neurotransmitters. The respective roles of each transmitter in the regulation of reward and addiction are still unknown. In this study, we showed that disruption of the gene that encodes VGLUT3 (Slc17a8) markedly increased cocaine self-administration in mice. Concomitantly, the amount of dopamine (DA) release was strongly augmented in the NAc of VGLUT3(-/-) mice because of a lack of signaling by metabotropic glutamate receptors. Furthermore, dendritic spines and glutamatergic synaptic transmission on medium spiny neurons were increased in the NAc of VGLUT3(-/-) mice. Increased DA and glutamate signaling in the NAc are hallmarks of addiction. Our study shows that TANs use glutamate to reduce DA release and decrease reinforcing properties of cocaine in mice. Interestingly, we also observed an increased frequency of rare variations in SLC17A8 in a cohort of severe drug abusers compared with controls. Our findings identify VGLUT3 as an unexpected regulator of drug abuse.
Pubmed
Web of science
Create date
29/10/2015 9:44
Last modification date
20/08/2019 15:12
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