Bidirectional Modulation of Intrinsic Excitability in Rat Prelimbic Cortex Neuronal Ensembles and Non-Ensembles after Operant Learning

Featured Paper of the Month – March 2018.

Study Authors Lorenzo Leggio, Mehdi Farokhnia, Mary Lee and Lisa Farinelli

Understanding the neurobiological substrates of excessive alcohol consumption may substantially facilitate efforts to develop better treatments. The cross-talk between the gastrointestinal and central nervous systems, often referred to as the gut–brain axis, is a promising yet underexplored domain in this regard. Ghrelin is a hormone primarily produced by the stomach and known for its role in increasing appetite and food intake (the “hunger hormone”). Recent animal and human studies suggest that ghrelin may also be involved in alcohol-seeking behaviors. For the first time in humans, NIDA/NIAAA scientists investigated whether and how exogenous ghrelin administration may impact alcohol intake and brain function in regions associated with alcohol-related behaviors in heavy-drinking, alcohol-dependent individuals. Results indicated that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered. Participants also started infusing alcohol sooner under ghrelin than placebo. Furthermore, ghrelin significantly influenced the brain activity in regions involved in alcohol- and food-seeking, including amygdala, medial orbitofrontal cortex, and nucleus accumbens. These findings shed light on the role of ghrelin in the neurobiology of excessive alcohol consumption, and together with previous human and rodent work, provide rationale for studying the ghrelin system as a novel treatment target for addictive disorders.

Publication Information

Farokhnia, M; Grodin, E N; Lee, M R; Oot, E N; Blackburn, A N; Stangl, B L; Schwandt, M L; Farinelli, L A; Momenan, R; Ramchandani, V A; Leggio, L

Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals. Journal Article

In: Mol Psychiatry, 2017, ISSN: 1476-5578 (Electronic); 1359-4184 (Linking).

Abstract | Links

@article{Farokhnia:2017aab,

title = {Exogenous ghrelin administration increases alcohol self-administration and modulates brain functional activity in heavy-drinking alcohol-dependent individuals.},

author = {M Farokhnia and E N Grodin and M R Lee and E N Oot and A N Blackburn and B L Stangl and M L Schwandt and L A Farinelli and R Momenan and V A Ramchandani and L Leggio},

url = {https://www.ncbi.nlm.nih.gov/pubmed/29133954},

doi = {10.1038/mp.2017.226},

issn = {1476-5578 (Electronic); 1359-4184 (Linking)},

year  = {2017},

date = {2017-11-14},

urldate = {2017-11-14},

journal = {Mol Psychiatry},

address = {Section on Clinical Psychoneuroendocrinology and Neuropsychopharmacology, National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse, National Institutes of Health, Bethesda, MD, USA.},

abstract = {Preclinical evidence suggests that ghrelin, a peptide synthesized by endocrine cells of the stomach and a key component of the gut-brain axis, is involved in alcohol seeking as it modulates both central reward and stress pathways. However, whether and how ghrelin administration may impact alcohol intake in humans is not clear. For, we believe, the first time, this was investigated in the present randomized, crossover, double-blind, placebo-controlled, human laboratory study. Participants were non-treatment-seeking alcohol-dependent heavy-drinking individuals. A 10-min loading dose of intravenous ghrelin/placebo (3 mcg kg(-1)) followed by a continuous ghrelin/placebo infusion (16.9 ng/kg/min) was administered. During a progressive-ratio alcohol self-administration experiment, participants could press a button to receive intravenous alcohol using the Computerized Alcohol Infusion System. In another experiment, brain functional magnetic resonance imaging was conducted while participants performed a task to gain points for alcohol, food or no reward. Results showed that intravenous ghrelin, compared to placebo, significantly increased the number of alcohol infusions self-administered (percent change: 24.97+/-10.65},

keywords = {},

pubstate = {published},

tppubtype = {article}

}