Endocrine, metabolic, and endocannabinoid alterations in rats exhibiting high anxiety-related behaviors

Abstract

Anxiety disorders are major risk factors for obesity. However, the mechanisms accounting for this susceptibility remain unclear. Animal models have proved to be useful tools for understanding the role of emotional functioning in the development and maintenance of metabolic alterations implicated in obesity. Here we sought to determine the predictive value of behavioral indices of anxiety for hormonal and metabolic imbalances in rats. Adult Lewis rats were screened on the elevated plus maze (EPM). K-means clustering was used to divide the rats into two groups based on their anxiety index in the EPM: low (LA) and high anxiety (HA) rats. This proxy of anxiety combines individual EPM parameters and accepted ratios into a single score. Four weeks later, we measured markers of endocrine and metabolic function. We found that relative LA rats, the HA rats exhibited reduced latencies to exit a modified light-dark conflict test. Our results show that the HA rats displayed increased corticosterone levels when compared to LA rats. Furthermore, the HA rats weighted more and exhibited an enhanced glycemic response to exogenously administered glucose during the glucose tolerance test, indicating glucose intolerance. Notably, when compared to LA rats, the HA rats showed higher circulating levels of the endogenous cannabinoid, 2-arachidonoyl-sn-glycerol (2-AG). Together, these data indicate that patterns of emotional reactivity associated with anxiety may share common pathological pathways with metabolic complications implicated in obesity. Uncovering metabolic risk factors for anxiety disorders have the potential to strongly impact how we treat mental illnesses.\n\nObjectiveTo test the hypothesis that indices of anxiety in the elevated plus maze have predictive value for alterations implicated in obesity, which include heightened emotional reactivity, and dysregulated corticosterone, glucose metabolism, and circulating endocannabinoid levels.