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Göteborgs universitets publikationer

Gut Peptide GLP-1 and Its Analogue, Exendin-4, Decrease Alcohol Intake and Reward

Författare och institution:
Rozita H. Shirazi (Institutionen för neurovetenskap och fysiologi); Suzanne L. Dickson (Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi); Karolina P Skibicka (Institutionen för neurovetenskap och fysiologi)
Publicerad i:
Plos One, 8 ( 4 )
Artikel, refereegranskad vetenskaplig
Fulltextlänk (lokalt arkiv):
Sammanfattning (abstract):
Glucagon-like-peptide-1 (GLP-1) is a gut- and neuro-peptide with an important role in the regulation of food intake and glucose metabolism. Interestingly, GLP-1 receptors (GLP-1R) are expressed in key mesolimbic reward areas (including the ventral tegmental area, VTA), innervated by hindbrain GLP-1 neurons. Recently GLP-1 has emerged as a potential regulator of food reward behavior, an effect driven by the mesolimbic GLP-1Rs. Its role in other reward behaviors remains largely unexplored. Since a considerable overlap has been suggested for circuitry controlling reward behavior derived from food and alcohol we hypothesized that GLP-1 and GLP-1Rs could regulate alcohol intake and alcohol reward. We sought to determine whether GLP-1 or its clinically safe stable analogue, Exendin-4, reduce alcohol intake and reward. To determine the potential role of the endogenous GLP-1 in alcohol intake we evaluated whether GLP-1R antagonist, Exendin 9-39, can increase alcohol intake. Furthermore, we set out to evaluate whether VTA GLP-1R activation is sufficient to reduce alcohol intake. Male Wistar rats injected peripherally with GLP-1 or Exendin-4 reduced their alcohol intake in an intermittent access two bottle free choice drinking model. Importantly, a contribution of endogenously released GLP-1 is highlighted by our observation that blockade of GLP-1 receptors alone resulted in an increased alcohol intake. Furthermore, GLP-1 injection reduced alcohol reward in the alcohol conditioned place preference test in mice. To evaluate the neuroanatomical substrate linking GLP-1 with alcohol intake/reward, we selectively microinjected GLP-1 or Exendin 4 into the VTA. This direct stimulation of the VTA GLP-1 receptors potently reduced alcohol intake. Our findings implicate GLP-1R signaling as a novel modulator of alcohol intake and reward. We show for the first time that VTA GLP-1R stimulation leads to reduced alcohol intake. Considering that GLP-1 analogues are already approved for clinical use, this places the GLP system as an exciting new potential therapeutic target for alcohol use disorders.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Medicinska grundvetenskaper ->
glucagon-like peptide-1, food-intake, ethanol-consumption, glucagon-like-peptide-1 receptor, parkinsons-disease, nucleus-accumbens, rodent models, rats, neurons, brain
Postens nummer:
Posten skapad:
2013-05-24 11:28
Posten ändrad:
2013-06-05 09:22

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