PubMed · 14831421
The source did not provide an abstract. Follow the original record for more information.
Explore connections, maps & timelines
H VOGT. 1951-04-06. [Drinking cures].. https://doi.org/10.1055/s-0028-1116698
Cite the original work for its findings. Save a collection to share your selection of sources.
KEEP EXPLORING
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.
Recent surveys suggest that positive outcomes in the pharmacotherapy of alcoholism may be obtained through drug combinations. The present study evaluated the effect of the combination of the opioid receptor antagonist, naltrexone, with the GABA(B) receptor agonist, baclofen, on the acquisition of alcohol drinking behavior in Sardinian alcohol-preferring (sP) rats. Rats were treated with either saline, 0.5 mg/kg naltrexone, 1mg/kg baclofen, or 0.5 mg/kg naltrexone plus 1mg/kg baclofen once a day for 10 days. Alcohol was offered immediately after the first drug injection under the 2-bottle regimen. Alcohol intake in saline-treated rats rose to 5-6 g/kg/day within a few days, indicative of a rapid acquisition of alcohol drinking behavior. Neither naltrexone nor baclofen, when given alone, affected alcohol drinking behavior. In contrast, the drug combination resulted in a significant reduction in daily alcohol intake and retardation in the acquisition of alcohol drinking behavior. These results suggest that combination of naltrexone plus baclofen may result in a synergistic reduction in alcohol intake in sP rats. These results are discussed in terms of naltrexone and baclofen exerting a concomitant and reciprocally potentiating inhibitory action on alcohol-induced activation of mesolimbic dopamine transmission.
We have recently shown that the abrupt discontinuation of chronic diazepam (DZM) administration facilitated ethanol consumption and enhanced the anxiolytic properties of ethanol. Tricyclic antidepressants such as desipramine and the selective serotonin reuptake inhibitor fluoxetine have been shown to reduce alcohol intake in rodent models of alcoholism and in alcoholics who are depressed. In the present study, we tested whether desipramine (1.25; 2.5 and 5 mg/kg, i.p.) and fluoxetine (5 mg/kg, i.p.) treatment affect both ethanol intake in a free-choice test and the anxiolytic effect induced by ethanol in DZM withdrawn rats. Adult male Wistar rats were submitted to a chronic DZM treatment (2 mg/kg per day) or vehicle (VEH) for 21 days. Twenty-four hours after the last DZM injection, rats were subjected to a free-choice paradigm between water and increasing ethanol concentrations with or without concurrent desipramine or fluoxetine administration (ethanol concentration (v/v) was increased every 4 days as follows: 2, 4, 6, 8 and 10% for the final 8 days). Chronic treatment with desipramine (24 days, twice a day, 2.5 and 5 mg/kg, i.p.) and fluoxetine (24 days, once a day; 5 mg/kg, i.p.) significantly reduced the amount of ethanol intake in DZM withdrawn rats. Furthermore, subchronic treatments with desipramine (4 days, twice a day, 2.5 and 5 mg/kg) and fluoxetine (4 days, once a day, 5 mg/kg, i.p.) blocked the anxiolytic-like behavior in the elevated plus maze induced by ethanol (1 g/kg; i.p.) in DZM withdrawn rats at day 5 of withdrawal. The present findings suggest that desipramine and fluoxetine could be effective pharmacological tools to prevent the subsequent development of ethanol dependence in rats previously exposed to DZM withdrawal.