Unpredictable stress and acute immune stimulation on anxiety measures in adult rats.

Abstract

Anxiety disorders and neuropsychiatric disorders have a complex and intricate relationship. In several neuropsychiatric disorders, anxiety is both a symptom and a risk factor. Acute and chronic stress exposure can both lead to anxiety disorders, and anxiety is a common neurobehavioral correlate of many stressors. There may be a connection between anxiogenesis and immunomodulation during stress, and research has indicated that the brain and its intricate neurotransmitter networks may affect immunological function. However, the interaction between chronic unpredictable mild stress (CUMS) and immunological stimulation in association with anxiety has been less extensively studied. Therefore, this study aimed to investigate the effect of CUMS on HPA-axis function, associated neurochemical changes, and anxiety-like behaviours following immune-activation by Lipopolysaccharide (LPS) in adult male rats. Rats were assigned to the following groups (n=6/group): control, CUMS, LPS, and CUMS+ LPS. Rats were subjected to CUMS protocol for 12 days and injected once with LPS two days before CUMS ended as per their respective groups. The open field test (OFT) and elevated plus maze (EPM) tests were carried out afterwards. Subsequently, animals were sacrificed to collect plasma, amygdala, hypothalamus, and hippocampus tissues to measure IL-6, 5-HT, BDNF concentrations, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), glucocorticoid receptor (GR), Nuclear Receptor Subfamily 3 Group C Member 1 (Nr3c1), and corticosterone (CORT) concentrations. Animals subjected to CUMS paradigm exhibited anxiolytic-like behaviour. Whereas LPS did not show overt changes. Additionally, there was a significant reduction in IL-6, GABA, ACTH, and CORT, whereas there was a significant increase in 5-HT and Nr3c1 concentrations following LPS and CUMS treatment, which may indicate suppressed neuro-inflammation. The significant increase in BDNF further supports the suppressed neuroinflammation, which may indicate the activation of a neuroprotective mechanism. Furthermore, a significant decrease in GABA concentration was noted in the amygdala in all the experimental groups. Our study highlights the buffering/ameliorating effect of the combination, highlighting the complex interactions between chronic stress and immune activation.