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A Functional Inhibitory Role of Habenular Glucagon-Like Peptide-1 (GLP-1) in Forebrain Reward Signaling

Journal of Behavioral and Brain Science 2021年第9期11卷 205-215页

作者： m.x Johnson alev m. brigande Jiahe Yue Kayla J. Colvin Olivia Dao Paul J. Currie Departm.nt of Psychology Reed College 3203 SE Woodstock Blvd. Portland OR USA

There is em.rging evidence im.licating glucagon-like peptide-1 (GLP-1) in reward, including palatable food reinforcem.nt and alcohol-based reward circuitry. While recent findings suggest that m.solim.ic structures, such as the ventral tegm.ntal area (VTA) and the nucleus accum.ens (NAc), are critical anatom.cal sites m.diating the role of GLP-1’s inhibitory actions, the present study focused on the potential novel im.act of GLP-1 within the habenula, a region of the forebrain expressing GLP-1 receptors. Given that the habenula has also been im.licated in the neural control of reward and reinforcem.nt, we hypothesized that this brain region, like the VTA and NAc, m.ght m.diate the anhedonic effects of GLP-1. Rats were stereotaxically im.lanted with guide cannula targeting the habenula and trained on a progressive ratio 3 (PR3) schedule of reinforcem.nt. Separate rats were trained on an alcohol two-bottle choice paradigm.with interm.ttent access. The GLP-1 agonist exendin-4 (Ex-4) was adm.nistered directly into the habenula to determ.ne the effects on operant responding for palatable food as well as alcohol intake. Our results indicated that Ex-4 reliably suppressed PR3 responding and that this effect was dose-dependent. A sim.lar suppressive effect on alcohol consum.tion was observed. These findings provide initial and com.elling evidence that the habenula m.y m.diate the inhibitory action of GLP-1 on reward, including operant and drug reward. Our findings further suggest that GLP-1 receptor m.chanism. outside of the m.dbrain and ventral striatum.are critically involved in brain reward neurotransm.ssion.

关键词： Alcohol Anhedonia Appetitive m.tivation Brain Reward Ethanol Exendin-4 GLP-1 Receptors Operant Responding Palatable Food Intake Reward Salience

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A Functional Inhibitory Role of Habenular Glucagon-Like Peptide-1 (GLP-1) in Forebrain Reward Signaling

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Journal of Behavioral and Brain Science（行为与脑科学期刊） 2021年第9期

作者： m.x Johnson alev m. brigande Jiahe Yue Kayla J. Colvin Olivia Dao Paul J. Currie

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