Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8516489 | Neuropharmacology | 2018 | 37 Pages |
Abstract
Gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the nervous system, plays an important role in biobehavioral processes that regulate alcohol seeking, food intake, and stress response. The metabotropic GABA-B receptor has been investigated as a potential therapeutic target for alcohol use disorder, by using orthosteric agonists (e.g., baclofen) and positive allosteric modulators. Whether and how pharmacological manipulation of the GABA-B receptor, in combination with alcohol intake, may affect feeding- and stress-related neuroendocrine pathways remains unknown. In the present randomized, double-blind, placebo-controlled study, thirty-four alcohol-dependent individuals received baclofen (30â¯mg/day) or placebo in a naturalistic outpatient setting for one week, and then performed a controlled laboratory experiment which included alcohol cue-reactivity, fixed-dose priming, and self-administration procedures. Blood samples were collected, and the following neuroendocrine markers were measured: ghrelin, leptin, amylin, glucagon-like peptide-1 (GLP-1), insulin, prolactin, thyroid-stimulating hormone, growth hormone, cortisol, and adrenocorticotropic hormone (ACTH). During the outpatient phase, baclofen significantly increased blood concentrations of acyl-ghrelin (pâ¯=â¯0.01), leptin (pâ¯=â¯0.01), amylin (pâ¯=â¯0.004), and GLP-1 (pâ¯=â¯0.02). Significant drugâ¯Ãâ¯time-point interaction effects for amylin (pâ¯=â¯0.001) and insulin (pâ¯=â¯0.03), and trend-level interaction effects for GLP-1 (pâ¯=â¯0.06) and ACTH (pâ¯=â¯0.10) were found during the laboratory experiment. Baclofen, compared to placebo, had no effect on alcohol drinking in this study (p'sâ¯â¥â¯0.05). Together with previous studies, these findings shed light on the role of the GABAergic system and GABA-B receptors in the shared neurobiology of alcohol-, feeding-, and stress-related behaviors.
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Authors
Mehdi Farokhnia, Mikela B. Sheskier, Mary R. Lee, April N. Le, Erick Singley, Sofia Bouhlal, Timmy Ton, Zhen Zhao, Lorenzo Leggio,