Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels

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dc.contributor.authorReddy, IA
dc.contributor.authorPino, JA
dc.contributor.authorWeikop, P
dc.contributor.authorOsses, N
dc.contributor.authorSørensen, G
dc.contributor.authorBering, T
dc.contributor.authorValle, C
dc.contributor.authorBluett, RJ
dc.contributor.authorErreger, K
dc.contributor.authorWortwein, G
dc.contributor.authorReyes, JG
dc.contributor.authorGraham, D
dc.contributor.authorStanwood, GD
dc.contributor.authorHackett, TA
dc.contributor.authorFink-Jensen, A
dc.contributor.authorTorres, GE
dc.contributor.authorGalli, A
dc.contributor.authorPatel, S
dc.date.accessioned2019-07-15T07:05:48Z
dc.date.available2019-07-15T07:05:48Z
dc.date.issued2016
dc.descriptionPara consultar fuente directa, visitar: https://www.nature.com/articles/tp201686
dc.description.abstractAgonism of the glucagon-like peptide 1 (GLP-1) receptor (GLP-1R) has been effective at treating aspects of addictive behavior for a number of abused substances, including cocaine. However, the molecular mechanisms and brain circuits underlying the therapeutic effects of GLP-1R signaling on cocaine actions remain elusive. Recent evidence has revealed that endogenous signaling at the GLP-1R within the forebrain lateral septum (LS) acts to reduce cocaine-induced locomotion and cocaine conditioned place preference, both considered dopamine (DA)-associated behaviors. DA terminals project from the ventral tegmental area to the LS and express the DA transporter (DAT). Cocaine acts by altering DA bioavailability by targeting the DAT. Therefore, GLP-1R signaling might exert effects on DAT to account for its regulation of cocaine-induced behaviors. We show that the GLP-1R is highly expressed within the LS. GLP-1, in LS slices, significantly enhances DAT surface expression and DAT function. Exenatide (Ex-4), a long-lasting synthetic analog of GLP-1 abolished cocaine-induced elevation of DA. Interestingly, acute administration of Ex-4 reduces septal expression of the retrograde messenger 2-arachidonylglycerol (2-AG), as well as a product of its presynaptic degradation, arachidonic acid (AA). Notably, AA reduces septal DAT function pointing to AA as a novel regulator of central DA homeostasis. We further show that AA oxidation product γ-ketoaldehyde (γ-KA) forms adducts with the DAT and reduces DAT plasma membrane expression and function. These results support a mechanism in which postsynaptic septal GLP-1R activation regulates 2-AG levels to alter presynaptic DA homeostasis and cocaine actions through AA.es_ES
dc.identifier.issn2158-3188
dc.identifier.other10.1038/tp.2016.86
dc.identifier.urihttps://hdl.handle.net/20.500.12536/84
dc.language.isoenes_ES
dc.sourceTranslational Psychiatryes_ES
dc.titleGlucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levelses_ES
dc.typeArtículo de revistaes_ES
uvm.carreraDepartamento de Ciencias Básicases_ES
uvm.escuelaDepartamento de Ciencias Básicases_ES
uvm.indexScopuses_ES
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