PubMed · 8173490
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D I Sherman, R Williams. 1994. Safe drinking limits?. https://doi.org/10.1111/j.1360-0443.1994.tb00883.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.
Evidence exists that the olfactory property of alcohol affects cerebral processes to influence the pattern of alcohol drinking in an experimental animal. In this study, the level of activity was quantified in the genetically selected alcohol-preferring P rats during exposure to the odor of 4 concentrations of alcohol. A Mini-Mitter transmitter was implanted intraperitoneally in each animal to record individual locomotor activity continuously, in terms of counts per unit time. In the first experiment, each rat was exposed between 1730 and 1930 h to the odor of 5%, 15%, 30%, or 60% alcohol placed in 2 petri dishes flanking both sides of each cage. The control condition was identical, except that the petri dishes were empty. In the second experiment, each rat was offered water and its individually preferred solution of alcohol in the drinking tubes during 1730 to 1930 h on alternate days of exposure to the odor of alcohol. During the odor condition alone, the 30% concentration of alcohol increased the activity counts significantly from the control level of 228.8 +/- 23.9 to 303.5 +/- 28.1 over the first 30 min of the 2-h test period. Plots of activity every 30 min for each alcohol solution, calculated as percent of control, also showed that the odor of 30% alcohol evoked significantly greater activity during the first and fourth intervals, in contrast to the exposure to 5%, 15%, and 60% alcohol, which failed to shift activity beyond the control level. When the P rats were exposed to 30% alcohol 24 h after 2 h of alcohol drinking, their profile of activity was concordant with that prior to alcohol drinking. These results demonstrate that the odor of a specific concentration of alcohol (i.e., 30%) selectively enhances the activity of the P rat. This could reflect an association of the sensory quality of alcohol with an anticipation of drinking. Finally, these experiments provide the first quantitative evidence that an olfactory cue associated with the unique odor of a specific solution of alcohol may determine the nature of the drinking response.
OBJECTIVE: To determine if moderate alcohol drinking increases circulating estradiol levels in postmenopausal women who are taking estrogen replacement. DESIGN: Randomized, double-blind, placebo-controlled crossover study of the effects of alcohol ingestion on plasma estradiol and estrone. SETTING: Inpatient Clinical Research Center. PARTICIPANTS: Twelve healthy postmenopausal women receiving oral estrogen (estradiol, 1 mg/day) and progestin (medroxyprogesterone acetate) replacement therapy were compared with 12 postmenopausal women who were not using estrogen replacement therapy (ERT). INTERVENTION: Each group drank alcohol (0.7 g/kg) and an isoenergetic (isocaloric) placebo (randomized sequence) on consecutive days. Women who were taking ERT were studied during the estrogen-only portion of their replacement cycle, and estrogen was administered each evening at 2100 hours. MAIN OUTCOME MEASURE: The impact of alcohol ingestion on plasma estradiol and estrone levels. RESULTS: Alcohol ingestion lead to a 3-fold increase in circulating estradiol in women on ERT; however, alcohol did not change estradiol significantly in control women who were not on ERT. In women using ERT, estradiol levels increased from 297 to 973 pmol/L (81 to 265 pg/mL) within 50 minutes (P<.001) during the ascending limb of the blood alcohol curve and remained significantly above baseline for 5 hours (P<.001). No significant increase in circulating estrone was detected in either group. However, estrone levels decreased after alcohol and placebo in women on ERT (P<.05). Blood alcohol levels did not differ significantly in women who used ERT and those who did not. Peak blood alcohol levels of 21 mmol/L were attained in each of the 2 groups within 50 to 60 minutes after drinking began. Changes in estradiol were significantly correlated with changes in blood alcohol levels on both the ascending (P<.001) and descending (P<.001) limb of the blood alcohol curve. CONCLUSIONS: Acute alcohol ingestion may lead to significant and sustained elevations in circulating estradiol to levels 300% higher than those targeted in clinical use of ERT. Potential health risks and benefits of the interactions between acute alcohol ingestion and ERT should be further evaluated.