Role of Ghrelin in Drug Abuse and Reward-Relevant Behaviors: A Burgeoning Field and Gaps in the Literature
A.R. Revitsky and L.C. Klein
Affiliation: Department of Biobehavioral Health, 219 Biobehavioral Health Building, The Pennsylvania State University, University Park, PA 16802, USA.
Keywords: Alcohol, dopamine, feeding, ghrelin, nucleus accumbens, reward pathway.
Ghrelin is a gut-brain hormone that regulates energy balance through food consumption. While ghrelin is well
known for its role in hypothalamic activation and homeostatic feeding, more recent evidence suggests that ghrelin also is
involved in hedonic feeding through the dopaminergic reward pathway. This paper investigated how ghrelin
administration (intraperitoneal, intracerebroventricular, or directly into dopaminergic reward-relevant brain regions)
activates the dopaminergic reward pathway and associated reward-relevant behavioral responses in rodents. A total of 19
empirical publications that examined one or more of these variables were included in this review. Overall, ghrelin
administration increases dopamine levels in the nucleus accumbens, as well as reward-relevant behaviors such as food
(both standard chow and palatable foods) and alcohol consumption. Ghrelin administration also increases operant
responding for sucrose, and conditioned place preference. Following a review of the small body of literature examining
the effects of ghrelin administration on the dopamine reward pathway, we present a model of the relationship between
ghrelin and dopaminergic reward activation. Specifically, ghrelin acts on ghrelin receptors (GHS-R1A) in the ventral
tegmental area (VTA) and lateral dorsal tegmental nucleus (LDTg) to stimulate the mesolimbic dopamine reward
pathway, which results in increased rewarding behaviors in rodents. Results from this review suggest that selective
antagonism of the ghrelin system may serve as potential treatment for addictive drug use. This review highlights gaps in
the literature, including a lack of examination of sex- or age-related differences in the effects of ghrelin on dopamine
reward processes. In light of vulnerability to drug abuse among female and adolescent populations, future studies should
target these individual difference factors.
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