Abstract
BACKGROUND: The context of alcohol consumption can influence an individual's experience and subsequent motivation, representing a point of potential clinical intervention in alcohol use disorder (AUD). Despite strong evidence for context-dependent influences on drug-cue reactivity, craving, seeking, and use, how multimodal contextual features interact to promote or suppress these behaviors is not well understood. METHODS: In adult male C57BL6/J mice, we conducted an unbiased alcohol conditioned place preference (CPP) procedure to determine the effects of proximal (sensory characteristics of the training apparatus) and distal (spatial characteristics of the training room) features of the training context on motivation for alcohol. RESULTS: We found that alcohol place preference was uniquely influenced by proximal and distal context features. Specifically, training with alcohol, but not saline, resulted in a robust preference for a context with black walls, coarse floor, and coffee scent, as well as closest proximity to a wall of the room. Further analysis revealed a hierarchy of contextual influence, wherein the distal feature outweighed the proximal features. Context features also influenced the rate of change of alcohol-induced locomotor activity during training which correlated with the strength of context preference at testing, consistent with the link between alcohol experience and motivation seen from rodents to human. CONCLUSIONS: Our findings indicate that both proximal and distal context features influence alcohol experience and subsequent motivation for alcohol. These findings highlight the importance of accounting for even subtle variations in training context, such as the location in a room. They further suggest that the varying motivational weight of different context levels could impact the development of AUD and be utilized to improve context-based treatment strategy outcomes. This approach offers a simple method to investigate the mechanisms by which multimodal context features influence appraisal and motivation.