Ghrelin System in Alcohol-dependent Subjects: Role of Plasma Ghrelin Levels in Alcohol Drinking and Craving

Overview

Journal Addict Biol

Specialty Psychiatry

Date 2011 Mar 12

PMID 21392177

Citations 70

Authors

Lorenzo Leggio

Anna Ferrulli

Silvia Cardone

Antonio Nesci

Antonio Miceli

Noemi Malandrino

Esmeralda Capristo

Benedetta Canestrelli

Palmiero Monteleone

George A Kenna

Robert M Swift

Giovanni Addolorato

Affiliations

Soon will be listed here.

Abstract

Animal studies suggest that the gut-brain peptide ghrelin plays an important role in the neurobiology of alcohol dependence (AD). Human studies show an effect of alcohol on ghrelin levels and a correlation between ghrelin levels and alcohol craving in alcoholics. This investigation consisted of two studies. Study 1 was a 12-week study with alcohol-dependent subjects, where plasma ghrelin determinations were assessed four times (T0-T3) and related to alcohol intake and craving [Penn Alcohol Craving Score (PACS) and Obsessive Compulsive Drinking Scale (OCDS)]. Serum growth hormone levels and assessment of the nutritional/metabolic status were also performed. Study 2 was a pilot case-control study to assess ghrelin gene polymorphisms (Arg51Gln and Leu72Met) in alcohol-dependent individuals. Study 1 showed no significant differences in ghrelin levels in the whole sample, while there was a statistical difference for ghrelin between non-abstinent and abstinent subjects. Baseline ghrelin levels were significantly and positively correlated with the PACS score at T1 and with all craving scores both at T2 and T3 (PACS, OCDS, obsessive and compulsive OCDS subscores). In Study 2, although there was a higher frequency of the Leu72Met ghrelin gene polymorphism in alcohol-dependent individuals, the distribution between healthy controls and alcohol dependent individuals was not statistically significant. This investigation suggests that ghrelin is potentially able to affect alcohol-seeking behaviors, such as alcohol drinking and craving, representing a new potential neuropharmacological target for AD.

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References

Monteleone P, Tortorella A, Castaldo E, Di Filippo C, Maj M . The Leu72Met polymorphism of the ghrelin gene is significantly associated with binge eating disorder. Psychiatr Genet. 2006; 17(1):13-6. DOI: 10.1097/YPG.0b013e328010e2c3. View

Anton R, Moak D, Latham P . The Obsessive Compulsive Drinking Scale: a self-rated instrument for the quantification of thoughts about alcohol and drinking behavior. Alcohol Clin Exp Res. 1995; 19(1):92-9. DOI: 10.1111/j.1530-0277.1995.tb01475.x. View

Tupala E, Tiihonen J . Dopamine and alcoholism: neurobiological basis of ethanol abuse. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(8):1221-47. DOI: 10.1016/j.pnpbp.2004.06.022. View

Landgren S, Jerlhag E, Zetterberg H, Gonzalez-Quintela A, Campos J, Olofsson U . Association of pro-ghrelin and GHS-R1A gene polymorphisms and haplotypes with heavy alcohol use and body mass. Alcohol Clin Exp Res. 2008; 32(12):2054-61. DOI: 10.1111/j.1530-0277.2008.00793.x. View

Jerlhag E, Egecioglu E, Landgren S, Salome N, Heilig M, Moechars D . Requirement of central ghrelin signaling for alcohol reward. Proc Natl Acad Sci U S A. 2009; 106(27):11318-23. PMC: 2703665. DOI: 10.1073/pnas.0812809106. View

Leggio L . Role of the ghrelin system in alcoholism: Acting on the growth hormone secretagogue receptor to treat alcohol-related diseases. Drug News Perspect. 2010; 23(3):157-66. DOI: 10.1358/dnp.2010.23.3.1429490. View

Calissendorff J, Danielsson O, Brismar K, Rojdmark S . Inhibitory effect of alcohol on ghrelin secretion in normal man. Eur J Endocrinol. 2005; 152(5):743-7. DOI: 10.1530/eje.1.01905. View

ZUNG W, RICHARDS C, SHORT M . Self-rating depression scale in an outpatient clinic. Further validation of the SDS. Arch Gen Psychiatry. 1965; 13(6):508-15. DOI: 10.1001/archpsyc.1965.01730060026004. View

Zimmermann U, Buchmann A, Steffin B, Dieterle C, Uhr M . Alcohol administration acutely inhibits ghrelin secretion in an experiment involving psychosocial stress. Addict Biol. 2007; 12(1):17-21. DOI: 10.1111/j.1369-1600.2006.00026.x. View

10.

Lutter M, Sakata I, Osborne-Lawrence S, Rovinsky S, Anderson J, Jung S . The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci. 2008; 11(7):752-3. PMC: 2765052. DOI: 10.1038/nn.2139. View

11.

Leggio L . Understanding and treating alcohol craving and dependence: recent pharmacological and neuroendocrinological findings. Alcohol Alcohol. 2009; 44(4):341-52. DOI: 10.1093/alcalc/agp026. View

12.

Date Y, Shimbara T, Koda S, Toshinai K, Ida T, Murakami N . Peripheral ghrelin transmits orexigenic signals through the noradrenergic pathway from the hindbrain to the hypothalamus. Cell Metab. 2006; 4(4):323-31. DOI: 10.1016/j.cmet.2006.09.004. View

13.

Jerlhag E, Egecioglu E, Dickson S, Svensson L, Engel J . Alpha-conotoxin MII-sensitive nicotinic acetylcholine receptors are involved in mediating the ghrelin-induced locomotor stimulation and dopamine overflow in nucleus accumbens. Eur Neuropsychopharmacol. 2008; 18(7):508-18. DOI: 10.1016/j.euroneuro.2008.02.006. View

14.

Jerlhag E, Egecioglu E, Dickson S, Andersson M, Svensson L, Engel J . Ghrelin stimulates locomotor activity and accumbal dopamine-overflow via central cholinergic systems in mice: implications for its involvement in brain reward. Addict Biol. 2006; 11(1):45-54. DOI: 10.1111/j.1369-1600.2006.00002.x. View

15.

Connelly D, Unwin J, Taberner P . The role of the blood glucose level in determining voluntary ethanol consumption in the LACG and diabetogenic C57BL strains of mice. Biochem Pharmacol. 1983; 32(2):221-6. DOI: 10.1016/0006-2952(83)90547-6. View

16.

Addolorato G, Leggio L . Safety and efficacy of baclofen in the treatment of alcohol-dependent patients. Curr Pharm Des. 2010; 16(19):2113-7. DOI: 10.2174/138161210791516440. View

17.

Kawahara Y, Kawahara H, Kaneko F, Yamada M, Nishi Y, Tanaka E . Peripherally administered ghrelin induces bimodal effects on the mesolimbic dopamine system depending on food-consumptive states. Neuroscience. 2009; 161(3):855-64. DOI: 10.1016/j.neuroscience.2009.03.086. View

18.

Jerlhag E, Egecioglu E, Dickson S, Douhan A, Svensson L, Engel J . Ghrelin administration into tegmental areas stimulates locomotor activity and increases extracellular concentration of dopamine in the nucleus accumbens. Addict Biol. 2007; 12(1):6-16. DOI: 10.1111/j.1369-1600.2006.00041.x. View

19.

Calissendorff J, Danielsson O, Brismar K, Rojdmark S . Alcohol ingestion does not affect serum levels of peptide YY but decreases both total and octanoylated ghrelin levels in healthy subjects. Metabolism. 2006; 55(12):1625-9. DOI: 10.1016/j.metabol.2006.08.003. View

20.

Asakawa A, Inui A, Kaga T, Yuzuriha H, Nagata T, Ueno N . Ghrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin. Gastroenterology. 2001; 120(2):337-45. DOI: 10.1053/gast.2001.22158. View