Abstract
Rationale
Conditions with sustained low-grade inflammation have high comorbidity with depression and anxiety and are associated with social withdrawal. The basolateral amygdala (BLA) is critical for affective and social behaviors and is sensitive to inflammatory challenges. Large systemic doses of lipopolysaccharide (LPS) initiate peripheral inflammation, increase BLA neuronal activity, and disrupt social and affective measures in rodents. However, LPS doses commonly used in behavioral studies are high enough to evoke sickness syndrome, which can confound interpretation of amygdala-associated behaviors.
Objectives and methods
The objectives of this study were to find a LPS dose that triggers mild peripheral inflammation but not observable sickness syndrome in adult male rats, to test the effects of sustained mild inflammation on BLA and social behaviors. To accomplish this, we administered single doses of LPS (0–100 μg/kg, intraperitoneally) and measured open field behavior, or repeated LPS (5 μg/kg, 3 consecutive days), and measured BLA neuronal firing, social interaction, and elevated plus maze behavior.
Results
Repeated low-dose LPS decreased BLA neuron firing rate but increased the total number of active BLA neurons. Repeated low-dose LPS also caused early disengagement during social bouts and less anogenital investigation and an overall pattern of heightened social caution associated with reduced gain of social familiarity over the course of a social session.
Conclusions
These results provide evidence for parallel shifts in social interaction and amygdala activity caused by prolonged mild inflammation. This effect of inflammation may contribute to social symptoms associated with comorbid depression and chronic inflammatory conditions.
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Data Availability
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
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The authors would like to acknowledge Dr. Soumyabrata Munshi for his advisement that led to the development of this project. This work was supported by the National Institutes of Health (MH084970 and MH118237 to J.A.R.). The funding agents did not have a role in study design, collection, analysis, interpretation of data, writing of the report, or in the decision to submit this work for publication.
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Loh, M.K., Stickling, C., Schrank, S. et al. Liposaccharide-induced sustained mild inflammation fragments social behavior and alters basolateral amygdala activity. Psychopharmacology 240, 647–671 (2023). https://doi.org/10.1007/s00213-023-06308-8
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DOI: https://doi.org/10.1007/s00213-023-06308-8