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Intravenous self‐administration of alcohol in rats—problems with translation to humans

Alcohol is consumed orally by humans, and oral self‐administration has been successfully modeled in laboratory animals. Over the last several years, attempts have been made to develop a procedure for the reliable intravenous (IV) self‐administration of alcohol in rodents. IV self‐administration would provide a better tool for investigating neurobiological mechanisms of alcohol reinforcement and dependence because confounding factors associated with oral self‐administration, such as variations in orosensory sensitivity to alcohol and/or its absorption, are avoided. A review of the literature shows that rats, mice and non‐human primates can initiate and maintain IV self‐administration of alcohol. However, there are 50‐ to 100‐fold interspecies differences in the reported alcohol infusion doses required. Most surprising is that the infusion dose (1–2 mg/kg) that reliably maintains IV alcohol self‐administration in rats results in total alcohol intakes of only 20–25 mg/kg/hour, which are unlikely to have significant pharmacological effects. The evidence to support IV self‐administration of such low doses of alcohol in rats as well as the potential biological mechanisms underlying such self‐administration are discussed. The minute amounts of alcohol shown to reliably maintain IV self‐administration behavior in rats challenge the relationship between their blood alcohol levels and the rewarding and reinforcing effects of alcohol.