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

Autor: Suzanne L. Dickson, Karolina P. Skibicka, Rozita H. Shirazi
Rok vydání: 2013
Předmět:
Male
Anatomy and Physiology
Eating Disorders
lcsh:Medicine
Stimulation
Alcohol
Social and Behavioral Sciences
Behavioral Neuroscience
Eating
chemistry.chemical_compound
Endocrinology
0302 clinical medicine
Glucagon-Like Peptide 1
Neurobiology of Disease and Regeneration
Psychology
lcsh:Science
Psychiatry
0303 health sciences
Multidisciplinary
digestive
oral
and skin physiology
Substance Abuse
Glucagon-like peptide-1
Ventral tegmental area
Mental Health
medicine.anatomical_structure
Neurology
Medicine
hormones
hormone substitutes
and hormone antagonists
Research Article
medicine.drug
endocrine system
medicine.medical_specialty
Alcohol Drinking
Endocrine System
Biology
03 medical and health sciences
Neuropharmacology
Dopamine
Internal medicine
medicine
Animals
Obesity
Rats
Wistar
Nutrition
030304 developmental biology
Diabetic Endocrinology
Behavior
Ethanol
Venoms
lcsh:R
Antagonist
Neuroendocrinology
Conditioned place preference
Rats
chemistry
Exenatide
lcsh:Q
Peptides
030217 neurology & neurosurgery
Neuroscience
Zdroj: PLoS ONE, Vol 8, Iss 4, p e61965 (2013)
PLoS ONE; Vol 8
PLoS ONE
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0061965
Popis: 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.
Databáze: OpenAIRE
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