The glucagon‐like peptide 1 receptor agonist liraglutide attenuates the reinforcing properties of alcohol in rodents

Abstract

The incretin hormone, glucagon‐like peptide 1 (GLP‐1), regulates gastric emptying, glucose‐dependent stimulation of insulin secretion and glucagon release, and GLP‐1 analogs are therefore approved for treatment of type II diabetes. GLP‐1 receptors are expressed in reward‐related areas such as the ventral tegmental area and nucleus accumbens, and GLP‐1 was recently shown to regulate several alcohol‐mediated behaviors as well as amphetamine‐induced, cocaine‐induced and nicotine‐induced reward. The present series of experiments were undertaken to investigate the effect of the GLP‐1 receptor agonist, liraglutide, on several alcohol‐related behaviors in rats that model different aspects of alcohol use disorder in humans. Acute liraglutide treatment suppressed the well‐documented effects of alcohol on the mesolimbic dopamine system, namely alcohol‐induced accumbal dopamine release and conditioned place preference in mice. In addition, acute administration of liraglutide prevented the alcohol deprivation effect and reduced alcohol intake in outbred rats, while repeated treatment of liraglutide decreased alcohol intake in outbred rats as well as reduced operant self‐administration of alcohol in selectively bred Sardinian alcohol‐preferring rats. Collectively, these data suggest that GLP‐1 receptor agonists could be tested for treatment of alcohol dependence in humans.

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

“…They were maintained in rooms with 20°C and 50 percent humidity and fed ad libitum. Outbred Rcc Han Wistar rats were selected for the intermittent access paradigm because they display a voluntary high and stable alcohol intake, causing pharmacologically relevant blood alcohol concentrations in the intermittent access model (Vallof et al 2016a).…”

“…Two distinct CPP tests were performed in mice as previously described (Jerlhag et al 2009;Vallof et al 2016a).…”

“…More specifically, gut-brain peptides, which have been traditionally known to regulate food intake and energy balance (Ahima & Antwi 2008), seem to play a pivotal role in mediating the reinforcing properties of alcohol and other drugs of abuse Abizaid et al 2011;Clifford et al 2012;Egecioglu, Engel, & Jerlhag 2013a;Suchankova et al 2013a;Engel & Jerlhag 2014;Vadnie et al 2014;Vallof et al 2016c). Notably, ghrelin, glucagon-like peptide-1 and neuromedin U have been shown to alter alcohol-induced reward phenotypes by acting on the mesolimbic dopamine system (Kraus et al 2005;Leggio et al 2011;Jerlhag et al 2011b;Landgren et al 2012;Suchankova et al 2013b;Leggio et al 2014;Vallof et al 2016a;Vallof et al 2016b). Other hormones, for example, amylin, have been recently studied for their role to control energy balance through gut-brain axis regulation (Reda, Geliebter, & Pi-Sunyer 2002;Lutz 2009).…”

Glucagon-like peptide 1 in the pathophysiology and pharmacotherapy of clinical obesity

“…Whilst 3 mg liraglutide has been shown to induce weight loss in man by reductions appetite pre-clinically, liraglutide attenuates the reinforcing properties of alcohol in vivo [209,210]. As such, perhaps GLP-1 agonism may attenuate produce its weight loss effects in part, by attenuating the negative reinforcement of hyperphagia in obesity.…”

A very mery Christmas

“…Separate from this study, Sahlgrenska researchers have found that liraglutide -a drug used to treat diabetes and obesity -might also have an effect on suppressing alcohol cravings 6 . This study, on mice and rats, shows that the drug interferes with the hormone GLP-1.…”