Behavioral economic demand for ethanol in Long Evans rats: Influence of choice context, sex, and vapor history

Abstract Rationale Behavioral economic demand analyses are widely used in human studies to quantify the motivational value of ethanol. However, the extent to which ethanol demand is modulated by alternative reinforcer availability and by biological factors, such as sex and history of ethanol vapor exposure, remains unstudied in preclinical animal models. Objectives This study used a novel rodent operant paradigm to examine how choice context, sex, and ethanol vapor exposure history influence both demand for ethanol and absolute intake. Methods Male and female Long Evans rats with or without a history of binge-like ethanol vapor exposure completed self-administration sessions under choice (sweetened ethanol and sucrose) and no-choice (sweetened ethanol only) conditions. Ethanol fixed-ratio (FR) increased across sessions to generate demand curves while sucrose remained under a FR5, when available. Cost-dependent changes in seeking behavior (demand curves) and absolute intake (g/kg) were evaluated using complementary analytical approaches. Results Increasing ethanol FR suppressed ethanol intake across all conditions. Vapor-exposed rats, who previously demonstrated reduced ethanol-directed choice behavior, demonstrated heightened sensitivity to ethanol price specifically when an alternative reinforcer was available. This context-dependent effect was absent under no-choice conditions. Notably, demand elasticity did not differ by sex, yet sex differences in absolute ethanol intake emerged, suggesting dissociable mechanisms. Substitution analyses revealed substantial individual heterogeneity. Conclusions These findings highlight the interaction between environmental and biological factors in shaping ethanol valuation, further characterizing self-administration as a dynamic process. Additionally, these results highlight the importance of measuring seeking and consummatory behaviors alongside achieved dose (g/kg) in oral self-administration paradigms.