Ghrelin system in alcohol-dependent subjects: role of plasma ghrelin levels in alcohol drinking and craving

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.

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

© 2011 The Authors, Addiction Biology © 2011 Society for the Study of Addiction.

Figures

Figure 1

Timeline of Study 1. GH: Growth Hormone; PACS: Penn Alcohol Craving Scale; OCDS: Obsessive Compulsive Drinking Scale; ODS: obsessive subscale of the OCDS; CDS: compulsive subscale of the OCDS; STAI: State and Trait Inventory; Zung-SDS: Zung Self-Rating Depression Scale.

Figure 2

Ghrelin changes during the four determinations (T0-T3); there were no statistical difference for ghrelin during the four different time intervals when we considered the total group of subjects (F=0.162, p=0.921).

Figure 3

Ghrelin changes of subjects who were abstinent vs. those who were not abstinent during the 12-week period were analyzed separately. There was a statistical difference in the changes of ghrelin between the two groups (F=4.913, p=0.012).

Figure 4

Relationship between baseline ghrelin levels (Ghrelin-T0) and Penn Alcohol Craving Scale (PACS) score at T1. Ghrelin-T0 was significantly and positively correlated with the PACS score at T1 (r= 0.423, p=0.012).

Figure 5

Relationship between baseline ghrelin levels (Ghrelin-T0) and craving scores at T2. Ghrelin-T0 was significantly and positively correlated with all craving scores at T2, namely the Penn Alcohol Craving Scale (PACS; r= 0.699, p

Figure 6

Relationship between baseline ghrelin levels (Ghrelin-T0) and craving scores at T3. Ghrelin-T0 was significantly and positively correlated with all craving scores at T3, namely the Penn Alcohol Craving Scale (PACS; r= 0.579, p