GABAA receptor signaling in caudal periaqueductal gray regulates maternal aggression and maternal care in mice

Maternal aggression (maternal defense) is exhibited by lactating females towards intruders and contributes to the protection of offspring. Enhancement of Gamma-Aminobutyric acid (GABA)A receptor signaling by benzodiazepines elevates maternal aggression, and we previously found indirect evidence (via c-Fos immunohistochemistry) that caudal periaqueductal gray (cPAG) and lateral septum (LS) could be sites where benzodiazepines increase aggression. We recently found that GABAA receptor signaling in LS modulates maternal aggression, and in this study, we tested the hypothesis that GABAA receptor signaling in cPAG also regulates this behavior. Site-directed injections to cPAG were made in lactating mice using the GABAA receptor antagonist, bicuculline (3–9 ng) or the GABAA receptor positive modulator, chlordiazepoxide (CDP), a benzodiazepine (2.5–20 μg). Maternal aggression, other maternal behaviors, and anxiety-like measures (using the light–dark box) were then examined. GABAA receptor positive modulator did not increase aggression, which could have resulted from a ceiling effect. However, 8 ng and 9 ng of bicuculline in cPAG significantly decreased maternal aggression without altering other maternal behaviors or light–dark box performance, suggesting some GABAA receptor signaling in cPAG is required for full maternal aggression expression. Additionally, 7 ng of bicuculline significantly increased licking/grooming of pups, and decreased the number of transitions between the light and dark compartments of the light–dark box without affecting aggression. Given these results indicating that antagonizing GABAA receptor in cPAG dose-dependently promotes offspring grooming behavior while impairing aggression, it is possible that the cPAG represents a key site for decision making (aggression versus other behaviors) in the lactating female.