Glucagon-Like Peptide-1 Receptors in Nucleus Accumbens, Ventral Hippocampus, and Lateral Septum Reduce Alcohol Reinforcement in Mice
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Glucagon-Like Peptide-1 Receptors in Nucleus Accumbens, Ventral Hippocampus, and Lateral Septum Reduce Alcohol Reinforcement in Mice. / Allingbjerg, Marie Louise; Hansen, Stine N.; Secher, Anna; Thomsen, Morgane.
In: Experimental and Clinical Psychopharmacology, Vol. 31, No. 3, 2023, p. 612-620.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Glucagon-Like Peptide-1 Receptors in Nucleus Accumbens, Ventral Hippocampus, and Lateral Septum Reduce Alcohol Reinforcement in Mice
AU - Allingbjerg, Marie Louise
AU - Hansen, Stine N.
AU - Secher, Anna
AU - Thomsen, Morgane
N1 - Publisher Copyright: © 2022 American Psychological Association
PY - 2023
Y1 - 2023
N2 - Glucagon-like peptide 1 (GLP-1) receptor agonists can decrease alcohol intake by central mechanisms that are still poorly understood. The lateral septum (LS) and the ventral/caudal part of the hippocampus are enriched in GLP-1 receptors, and activity in these regions was shown to modulate reward-related behaviors. Using microinfusions of the GLP-1 receptor agonist exendin-4 in mice trained to self-administer oral alcohol in an operant assay, we tested whether pharmacological stimulation of GLP-1 receptors in hippocampus and LS decrease alcohol self-administration. We report that infusion of exendin-4 in the ventral hippocampus or LS was sufficient to reduce alcohol self-administration with as large effect sizes as we previously reported with systemic exendin-4 administration. Infusion of exendin-4 into the nucleus accumbens also reduced alcohol self-administration, as anticipated based on earlier reports, while infusion of exendin-4 into the caudateputamen (dorsal striatum) had little effect, consistent with lack of GLP-1 receptor expression in this region. The distribution of exendin-4 after infusion into the LS or caudate putamen was visualized using a fluorescently labeled ligand. These findings add to our understanding of the circuit-level mechanisms underlying the ability of GLP-1 receptor agonists to reduce alcohol self-administration.
AB - Glucagon-like peptide 1 (GLP-1) receptor agonists can decrease alcohol intake by central mechanisms that are still poorly understood. The lateral septum (LS) and the ventral/caudal part of the hippocampus are enriched in GLP-1 receptors, and activity in these regions was shown to modulate reward-related behaviors. Using microinfusions of the GLP-1 receptor agonist exendin-4 in mice trained to self-administer oral alcohol in an operant assay, we tested whether pharmacological stimulation of GLP-1 receptors in hippocampus and LS decrease alcohol self-administration. We report that infusion of exendin-4 in the ventral hippocampus or LS was sufficient to reduce alcohol self-administration with as large effect sizes as we previously reported with systemic exendin-4 administration. Infusion of exendin-4 into the nucleus accumbens also reduced alcohol self-administration, as anticipated based on earlier reports, while infusion of exendin-4 into the caudateputamen (dorsal striatum) had little effect, consistent with lack of GLP-1 receptor expression in this region. The distribution of exendin-4 after infusion into the LS or caudate putamen was visualized using a fluorescently labeled ligand. These findings add to our understanding of the circuit-level mechanisms underlying the ability of GLP-1 receptor agonists to reduce alcohol self-administration.
KW - Alcohol self-administration
KW - Ethanol
KW - Incretin hormone
KW - Lateral septum
KW - Operant behavior
U2 - 10.1037/pha0000620
DO - 10.1037/pha0000620
M3 - Journal article
C2 - 36480394
AN - SCOPUS:85145822931
VL - 31
SP - 612
EP - 620
JO - Experimental and Clinical Psychopharmacology
JF - Experimental and Clinical Psychopharmacology
SN - 1064-1297
IS - 3
ER -
ID: 338945264