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

Research output: Contribution to journalJournal articleResearchpeer-review

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Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels. / Reddy, I A; Pino, J A; Weikop, P; Osses, N; Sørensen, G; Bering, T; Valle, C; Bluett, R J; Erreger, K; Wörtwein, G.; Reyes, J G; Graham, D; Stanwood, G D; Hackett, T A; Patel, S; Fink-Jensen, A; Torres, G E; Galli, A.

In: Translational Psychiatry, Vol. 6, e809, 2016.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Reddy, IA, Pino, JA, Weikop, P, Osses, N, Sørensen, G, Bering, T, Valle, C, Bluett, RJ, Erreger, K, Wörtwein, G, Reyes, JG, Graham, D, Stanwood, GD, Hackett, TA, Patel, S, Fink-Jensen, A, Torres, GE & Galli, A 2016, 'Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels', Translational Psychiatry, vol. 6, e809. https://doi.org/10.1038/tp.2016.86

APA

Reddy, I. A., Pino, J. A., Weikop, P., Osses, N., Sørensen, G., Bering, T., ... Galli, A. (2016). Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels. Translational Psychiatry, 6, [e809]. https://doi.org/10.1038/tp.2016.86

Vancouver

Reddy IA, Pino JA, Weikop P, Osses N, Sørensen G, Bering T et al. Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels. Translational Psychiatry. 2016;6. e809. https://doi.org/10.1038/tp.2016.86

Author

Reddy, I A ; Pino, J A ; Weikop, P ; Osses, N ; Sørensen, G ; Bering, T ; Valle, C ; Bluett, R J ; Erreger, K ; Wörtwein, G. ; Reyes, J G ; Graham, D ; Stanwood, G D ; Hackett, T A ; Patel, S ; Fink-Jensen, A ; Torres, G E ; Galli, A. / Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels. In: Translational Psychiatry. 2016 ; Vol. 6.

Bibtex

@article{4fb2bcb943fe430a8cc122b1c4032409,
title = "Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels",
abstract = "Agonism 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.",
author = "Reddy, {I A} and Pino, {J A} and P Weikop and N Osses and G S{\o}rensen and T Bering and C Valle and Bluett, {R J} and K Erreger and G. W{\"o}rtwein and Reyes, {J G} and D Graham and Stanwood, {G D} and Hackett, {T A} and S Patel and A Fink-Jensen and Torres, {G E} and A Galli",
year = "2016",
doi = "10.1038/tp.2016.86",
language = "English",
volume = "6",
journal = "Translational Psychiatry",
issn = "2158-3188",
publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Glucagon-like peptide 1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels

AU - Reddy, I A

AU - Pino, J A

AU - Weikop, P

AU - Osses, N

AU - Sørensen, G

AU - Bering, T

AU - Valle, C

AU - Bluett, R J

AU - Erreger, K

AU - Wörtwein, G.

AU - Reyes, J G

AU - Graham, D

AU - Stanwood, G D

AU - Hackett, T A

AU - Patel, S

AU - Fink-Jensen, A

AU - Torres, G E

AU - Galli, A

PY - 2016

Y1 - 2016

N2 - Agonism 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.

AB - Agonism 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.

U2 - 10.1038/tp.2016.86

DO - 10.1038/tp.2016.86

M3 - Journal article

C2 - 27187231

VL - 6

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

M1 - e809

ER -

ID: 163128466