Abstract
Rationale
Understanding the neurobiological mechanisms mediating dominance and competitive aggression is essential to understanding the development and treatment of various psychiatric disorders. Previous research suggests that these mechanisms are both sexually differentiated and influenced substantially by social experience. In numerous species, GABAA receptors in the lateral septum have been shown to play a significant role in aggression in males. However, very little is known about the role of these GABAA receptors in female aggression, the role of social experience on GABAA receptor–mediated aggression, or the roles of different GABAA subtypes in regulating aggression.
Objectives
Thus, in the following set of experiments, we determined the role of social experience in modulating GABAA receptor–induced aggression in both male and female Syrian hamsters, with a particular focus on the GABAA receptor subtype mediating these effects.
Results
Activation of GABAA receptors in the dorsal lateral septum increased aggression in both males and females. Social housing, however, significantly decreased the ability of GABAA receptor activation to induce aggression in males but not females. No significant differences were observed in the effects of GABAA receptor activation in dominant versus subordinate group-housed hamsters. Finally, examination of potential GABAA receptor subtype specificity revealed that social housing decreased the ratio of δ extrasynaptic to γ2 synaptic subunit GABAA receptor mRNA expression in the anterior dorsal lateral septum, while activation of δ extrasynaptic, but not γ2 synaptic, GABAA receptors in the dorsal lateral septum increased aggression.
Conclusions
These data suggest that social experience can have profound effects on the neuronal mechanisms mediating aggression, especially in males, and that δ extrasynaptic GABAA receptors may be an important therapeutic target in disorders characterized by high levels of aggression.
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Abbreviations
- GABAAR:
-
GABAA receptor
- dLS:
-
Dorsal lateral septum
- adLS:
-
Anterior dorsal lateral septum
- CDP:
-
Chlordiazepoxide
- THIP:
-
Gaboxadol
- MS:
-
Medial septum
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Acknowledgments
We thank Dr. Joseph I. Terranova for his assistance with these experiments.
Funding
This work was supported by the National Institutes of Health under award number F31MH113367 to JMB, F32NS092545 to JCW, and R01MH109302 and R01MH110212 to HEA and funds from the Brains and Behavior Program at Georgia State University.
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Borland, J.M., Walton, J.C., Norvelle, A. et al. Social experience and sex-dependent regulation of aggression in the lateral septum by extrasynaptic δGABAA receptors. Psychopharmacology 237, 329–344 (2020). https://doi.org/10.1007/s00213-019-05368-z
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DOI: https://doi.org/10.1007/s00213-019-05368-z