calcitonin and Alcoholism

The objective of this study was to study the ability of biological markers of alcohol consumption in differentiating subjects below weekly consumption of 400 or 600 g of absolute ethanol from those above, and to study the effect of intranasal calcitonin on alcohol drinking. A prospective 12-week double-blind study that used anonymous data collection with drinking diaries was done. The drug that was studied (calcitonin or placebo) was used during study weeks 5-8. This study was performed at the research unit of a university hospital. The subjects consisted of 59-nine men aged 26 to 57 years who considered themselves as regular but modest drinkers and were recruited by advertisements. The measurements were obtained from monthly questionnaires and daily anonymous diaries for alcohol drinking data, and biological markers of alcohol consumption (aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, beta hexosaminidase, and carbohydrate deficient transferrin). The results indicated intranasal calcitonin with a dose of 200 IU three times a week had no effect on alcohol use. All biological markers studied had only a modest ability to differentiate those with weekly alcohol consumption of 400 or 600 g or over from those below these limits. The areas under receiver operating characteristic (ROC) curve with the limit 400 g/week were 0.71 for aspartate aminotransferase, 0.61 for alanine aminotransferase, 0.74 for gamma-glutamyl transpeptidase, 0.68 for beta-hexosaminidase, and 0.78 for carbohydrate deficient transferrin. Respective numbers for the 600-g limit were more uniform. As evaluated by ROC analysis, carbohydrate deficient transferrin was the best biological marker to find men with weekly alcohol consumption over 400 g. Intranasal salmon calcitonin had no affect on alcohol drinking.

Topics: Administration, Intranasal; Adult; Alanine Transaminase; Alcohol Drinking; Alcoholism; Aspartate Aminotransferases; beta-N-Acetylhexosaminidases; Biomarkers; Calcitonin; Double-Blind Method; Enzymes; gamma-Glutamyltransferase; Humans; Male; Middle Aged; Prospective Studies; Transferrin

Alcohol use disorder is a complex neuropsychiatric disorder affecting both males and females worldwide; however, the efficacy of current pharmacotherapies varies. Recent advances show that gut-brain peptides, like amylin, regulate alcohol behavioural responses by acting on brain areas involved in alcohol reward processes. Thus, the activation of amylin receptors (AMYRs) by salmon calcitonin (sCT) decreases alcohol behaviours in male rodents. Given that sCT also activates the sole calcitonin receptor (CTR), studies of more selective AMYR agonists in both male and female rodents are needed to explore amylinergic modulation of alcohol behaviours. Therefore, we investigated the effects of repeated administration of a selective long-acting AMYR agonist, NNC0174-1213 (AM1213), on alcohol, water and food intake, as well as body weight in male and female rats chronically exposed to alcohol. We confirm our previous studies with sCT in male rats, as repeated AM1213 administration for 2 weeks initially decreased alcohol intake in both male and female rats. However, this reduction ceases in both sexes on later sessions, accompanied by an increase in males. AM1213 reduced food intake and body weight in both male and female rats, with sustained body weight loss in males after discontinuation of the treatment. Moreover, AM1213 administration for 3 or 7 days, differentially altered dopamine, serotonin and their metabolites in the reward-related areas in males and females, providing tentative, but different, downstream mechanism through which selective activation of AMYR may alter alcohol intake. Our data provide clarified insight into the importance of AMYRs for alcohol intake regulation in both sexes.

Topics: Alcohol Drinking; Alcoholism; Amylin Receptor Agonists; Animals; Body Weight; Calcitonin; Eating; Female; Male; Rats; Rats, Wistar; Reward; Water

Recent findings have identified salmon calcitonin (sCT), an amylin receptor agonist and analogue of endogenous amylin, as a potential regulator of alcohol-induced activation of the mesolimbic dopamine system and alcohol consumption. Providing that the role of amylin signalling in alcohol-related behaviours remains unknown, the present experiments investigate the effect of sCT on these behaviours and the mechanisms involved. We showed that repeated sCT administration decreased alcohol and food intake in outbred rats. Moreover, single administration of the potent amylin receptor antagonist, AC187, increased short-term alcohol intake in outbred alcohol-consuming rats, but did not affect food intake. Acute administration of sCT prevented relapse-like drinking in the "alcohol deprivation effect" model in outbred alcohol-experienced rats. Additionally, acute sCT administration reduced operant oral alcohol self-administration (under the fixed ratio 4 schedule of reinforcement) in selectively bred Sardinian alcohol-preferring rats, while it did not alter operant self-administration (under the progressive ratio schedule of reinforcement) of a highly palatable chocolate-flavoured beverage in outbred rats. Lastly, we identified differential amylin receptor expression in high compared to low alcohol-consuming rats, as reflected by decreased calcitonin receptor and increased receptor activity modifying protein 1 expression in the nucleus accumbens (NAc) of high consumers. Collectively, our data suggest that amylin signalling, especially in the NAc, may contribute to reduction of various alcohol-related behaviours.

Topics: Alcohol Drinking; Alcoholism; Amylin Receptor Agonists; Animals; Behavior, Animal; Calcitonin; Disease Models, Animal; Drinking Behavior; Eating; Male; Nucleus Accumbens; Peptide Fragments; Rats; Rats, Wistar; Receptors, Islet Amyloid Polypeptide; Self Administration