Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

Abstract

Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use disorders (AUD). In this review, we discuss the effects of several gut-brain peptides on alcohol-related behaviors and the potential mechanisms by which these gut-brain peptides may interfere with alcohol-induced changes in corticostriatal-limbic circuitry. This review provides a summary of current knowledge on gut-brain peptides focusing on five peptides: neurotensin, glucagon-like peptide 1, ghrelin, substance P, and neuropeptide Y. Our review will be helpful to develop novel therapeutic targets for AUD.

Intermittent access to a nutritionally complete high-fat diet attenuates alcohol drinking in rats

“…GI peptides regulate the intake and reinforcing properties of food and alcohol by acting within the brain reward circuitry (Egecioglu et al, 2013; Shirazi et al, 2013; Vadnie et al, 2014). Specifically, previous reports from our lab and others, indicate that GLP-1 and ghrelin are capable of influencing alcohol intake (Davis et al, 2012; Leggio et al, 2012; Shirazi et al, 2013).…”

“…Ghrelin is also elevated in abstinent alcoholics (Leggio et al, 2012) and exogenous ghrelin stimulates alcohol craving in patients and rodents (Jerlhag et al, 2009; Leggio et al, 2012). In relation to alcohol intake, the majority of data collected so far indicate a positive relationship between ghrelin and alcohol intake (Jerlhag et al, 2009; Leggio et al, 2014; Vadnie et al, 2014). Interestingly, rats in the HFD exposure group displayed significantly elevated basal levels of acyl-ghrelin (Figure 7b), the active form of ghrelin (Kirchner et al, 2009), even though they consumed less alcohol.…”

“…This is based on observations that like drugs of abuse, both sweet and fatty foods are capable of activating brain reward circuitry (Tomasi and Volkow, 2013; Volkow et al, 2012). In this context, feeding peptides that control appetite and energy metabolism also regulate the intake and reinforcing properties of alcohol (Vadnie et al, 2014). These feeding peptides are released during anticipation of scheduled meals, ingestion and storage of calories, calorie restriction and learned responses that facilitate approach behavior to food (Drazen et al, 2006; Kanoski et al, 2013; Vahl et al, 2010).…”

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

“…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).…”

The Role of Psychotropic Medications in the Management of Anorexia Nervosa: Rationale, Evidence and Future Prospects

“…Nevertheless, those agents could be investigated in animal models of AN. A potential for the eating disorders field from relevant research in the addiction literature is on gastrointestinal peptides that are active in the brain [176]. Those peptides include substance P, neurotensin, ghrelin, neuropeptide Y and glucagon like peptide 1.…”