While ghrelin s role in addictive behaviors
While ghrelin's role in addictive behaviors has been most extensively explored with alcohol, ghrelin has also been implicated in biobehavioral substrates of other drugs of abuse. For example, preclinical experiments suggest that GHS-R1a blockade may improve nicotine [155,156], opioids [, , , ], and stimulants [116,, , , ] use outcomes. These findings across various drugs of abuse further highlight the prominent role of the ghrelin system in modulating neurobiological mechanisms that underlie drug addiction. As such, further work on the potential role of the ghrelin system, and other feeding-related pathways, in substance use disorder is warranted. It is also important to note ghrelin closely interacts with a myriad of metabolic and stress-related Isotretinoin receptor (e.g., leptin, insulin, glucagon-like peptide-1, cortisol) that have been shown to contribute to the pathophysiology of AUD and other substance use disorders [, , , , , , , , , , ]. Therefore, ghrelin's effect on addictive behaviors and alcohol-related outcomes may be, in part, mediated through cross-talk with these other neuroendocrine effectors.
Funding This work was supported by NIH intramural funding ZIA-AA000218 (Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology; PI: Dr. Lorenzo Leggio), jointly supported by the NIAAA Division of Intramural Clinical and Biological Research and the NIDA Intramural Research Program.
Conflict of interest
Introduction Feeding is a complex and multifaceted behavior that often occurs in the absence of metabolic need. Decisions about feeding, such as when to eat, what to eat, and how much to eat, are strongly rooted in learned associations between environmental cues, interoceptive cues (e.g., hunger, satiety), and the sensory properties of specific foods (e.g., flavor, palatability) (Cornell et al., 1989, Davidson et al., 2014, Halford et al., 2004, Holland et al., 2002, Kanoski and Grill, 2017). Social cues, in particular, are potent environmental regulators of feeding behavior. For example, studies show that people often consume more food when in groups compared to eating alone, a phenomenon known as the “social facilitation of feeding” (Herman, 2015). Social cues can also reduce food consumption depending on social-derived norms and the context (Herman et al., 2003). In rodents, a behavioral paradigm known as the “Social Transmission of Food Preference” (STFP) has been widely used to examine social food-related learning. In this task learned associations formed between a socially-transmitted olfactory food cue (e.g. food odor detected from another animal) have a robust effect on an animal's subsequent food preferences (e.g. preference for the food associated with the odor smelled on the other animal's breath) (Brightwell et al., 2005, Countryman and Gold, 2007, Countryman et al., 2005, Galef et al., 2005, Galef and Whiskin, 2003, Gold et al., 2011, Hegde et al., 2016, Matta et al., 2017). Using a rodent model to better understand the neural substrates that facilitate STFP and other learned aspects of feeding behavior is an important step towards elucidating the neurobiological pathways controlling higher-order aspects of food intake and body weight regulation. The stomach-derived hormone ghrelin is emerging as a possible biological mechanism that links learning, memory, and ingestive behaviors (Cone et al., 2015, Hsu et al., 2016). Traditionally known as a “hunger” hormone, recent data suggest that ghrelin might be more aptly described as a conditioned, meal-anticipatory hormone. This notion is supported by findings that circulating ghrelin secretion can be entrained in both rodents and humans, resulting in conditioned cephalic responses through which ghrelin levels rise prior to an anticipated meal (Cummings et al., 2001, Drazen et al., 2006, Frecka and Mattes, 2008). Research has also demonstrated that ghrelin signaling modulates feeding in response to discrete conditioned food cues (e.g., lights, tones) (Dailey et al., 2016, Kanoski et al., 2013) and animals with transgenic ghrelin receptor (GHSR-1A) deletion show a lack of meal anticipatory behaviors in response to either circadian or environmental conditioned food cues (Blum et al., 2009, Davis et al., 2011, Lamont et al., 2014, Walker et al., 2012). Considering the important role of ghrelin signaling on learned feeding responses, it is feasible that ghrelin signaling in the brain might also regulate feeding behaviors stimulated by learned, social-related food cues.