Minocycline treatment reduces anxiety- and depressive-like behaviors in a genetic model of internalizing mood disorders

Maras PM, Daugherty J, Hebda-Bauer EK, Watson SJ Jr, Akil H
Society for Neuroscience. 2018.


Many psychological disorders, such as anxiety and depression, are strongly influenced by genetic factors. Our laboratory uses a selective breeding technique to study the neurobiological mechanisms underlying the propensity to develop mood disorders. Specifically, we have found that rats bred for high locomotor responses when placed into a novel environment (bHRs) exhibit low anxiety and are resilient to depression, whereas rats bred for low locomotor responses to novelty (bLRs) are highly anxious and vulnerable to depression. Among the possible factors underlying bHR/bLR differences in affective temperament, recent mRNA expression studies in our lab suggest that bLRs have elevated expression of key microglia-related genes within their hippocampus compared to bHRs, and these differences emerge as early as postnatal day 14. To test whether elevations in microglia activation are functionally related to the vulnerability of bLRs, we administered the antibiotic drug minocycline, which has been shown to suppress microglia, for 2 weeks in adult bLRs. We examined the behavioral effects of minocycline treatment under non-stress conditions (basal), as well as when it was administered concurrently with chronic mild stress. Whereas minocycline reduced anxiety in the elevated plus maze in non-stressed bLRs, the drug was ineffective when bLRs were challenged with stress, suggesting that microglia may play a role in the basal anxiety phenotype of bLRs, but not their anxiety response to stress. In contrast, minocycline reduced immobility time in the forced swim test regardless of stress exposure, indicating a robust anti-depressant effect of the drug in genetically vulnerable rats. Taken together, these studies reveal that natural variations in affective temperament may be at least partially explained by underlying differences in microglia gene expression and/or activation. To determine the role of microglia in the organization of emotional brain circuits, ongoing studies are examining the effects of early-life minocycline treatment on the emergence of the bLR phenotype.