Acquisition of Oral Ethanol Self‐administration in Long‐Evans Rats: Model Validation for Treatment of Alcohol Use Disorders
Authors: Berquist Michael D , Fantegrossi William E 
Published: June 2021

Alcohol use disorder (AUD) is a prevalent (>15 million Americans) chronic condition characterized by compulsive alcohol use and dependency. Less than 10% of people with an AUD seek treatment, and less than 20% of people with an alcohol disorder who receive treatment will remain abstinent for a full year. As such, it is important to identify adjunct treatment strategies for AUDs and methods for promoting long‐term alcohol abstinence. The goals of the present study were to establish and validate a model of ethanol consumption in laboratory rats, in order to evaluate the effectiveness of psychedelic drugs in persistently reducing ethanol consumption. Adult male Long‐Evans rats (N=16) were trained to orally self‐administer 20% ethanol using an intermittent access two‐bottle choice procedure in their home cages. Rats were given opportunities to drink from a bottle containing 20% ethanol or a bottle containing water in three 24‐hour sessions per week; on intervening days, rats were given two bottles of water. Ethanol consumption and preference, total fluid consumption, and food intake were quantified during acquisition, until rats showed stable ethanol intake and preference with no apparent trend (considered at 17 ethanol access sessions). During the final three sessions of acquisition, ethanol intake was 4.87 g/kg/24 hours and preference was ~50%. Following acquisition, rats were divided into high consumers (n=8) and low consumers (n=8) using a median split. During the final three ethanol acquisition sessions, high consumers showed significantly greater levels of intake (7.33 g/kg/24 hours) and preference (72%) compared to the intake (2.5 g/kg/24 hours) and preference (26%) of low consumers. After the acquisition phase, all rats were given intermittent, 24‐hour access to varying concentrations of ethanol (5, 10, 20, 40% v/v) to generate ethanol concentration effect curves (ECEC). In the complete sample of rats, peak intake occurred at 20% ethanol, however preference was greater at 5% (86% preference) and 10% (75% preference) ethanol concentrations. High consumers and low consumers all showed peak intake at 20% ethanol, but the ECEC for ethanol preference in high consumers was upwardly shifted compared to low consumers. Furthermore, a regression analysis revealed that the point of indifference in ethanol preference (i.e., a 50% preference) occurred at 31.7% ethanol for high consumers, but at 13.97% ethanol in low consumers. Thus, these results indicate that rats' ethanol consumption patterns during the acquisition phase of the experiment are predictive of their intake and preference when given access to varying ethanol concentrations. Following the initial ECEC determination, the effects of naltrexone pretreatment on ethanol intake and preference will be assessed for model validation. Thereafter, the capacity of the psychedelic serotonin 5‐HT2A agonist 2,5‐dimethoxy‐4‐iodoamphetamine (DOI) to reduce ethanol intake and preference in rats will be assessed. It is hypothesized that naltrexone will produce a global reduction in consummatory behaviors in rats, while DOI is expected to specifically decrease ethanol consumption, but have no effect on water or food consumption.Support or Funding InformationNIDA T32DA022981This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.