PubMed · 371443
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J A Ewing. 1979. Goals: abstinence or controlled drinking?. https://doi.org/10.1111/j.1530-0277.1979.tb04757.x
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Excessive alcohol consumption is a major health and social issue in our society. Pharmacologic administration of the endocrine hormone fibroblast growth factor 21 (FGF21) suppresses alcohol consumption through actions in the brain in rodents, and genome-wide association studies have identified single nucleotide polymorphisms in genes involved with FGF21 signaling as being associated with increased alcohol consumption in humans. However, the neural circuit(s) through which FGF21 signals to suppress alcohol consumption are unknown, as are its effects on alcohol consumption in higher organisms. Here, we demonstrate that administration of an FGF21 analog to alcohol-preferring non-human primates reduces alcohol intake by 50%. Further, we reveal that FGF21 suppresses alcohol consumption through a projection-specific subpopulation of KLB-expressing neurons in the basolateral amygdala. Our results illustrate how FGF21 suppresses alcohol consumption through a specific population of neurons in the brain and demonstrate its therapeutic potential in non-human primate models of excessive alcohol consumption.
The development and characterization of an animal model to study mechanisms underlying abnormal alcohol-seeking behavior have been described. Raised by genetic means, it demonstrates the importance of genetic factors in this behavior. It has allowed the elucidation of neural pathways and neurotransmitter systems that subserve alcohol-seeking behavior. It offers the potential for screening new medications for the treatment of alcoholism, based upon these kinds of newly discovered knowledge.
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