Abstract

The bidirectional communication between neuroendocrine and immune components maintains the physiological and psychological homeostasis of animals. The systemic administration of lipopolysaccharide (LPS) (an immune stressor) activates the hypothalamic–pituitary–adrenal (HPA) axis. The PD 149163 (PD), a neurotensin agonist, functions as an antipsychotic drug in psychosis and behavioral impairment. The present study aimed to address the role of PD in the HPA axis regulation which is not known. Swiss albino adult female mice were randomly divided into four groups (six mice/group): control received saline 0.9% NaCl; LPS received 1 mg/kg BW for 5 days; LPS + PD received LPS 1 mg/kg BW for 5 days and after that treated with PD 300 µg/kg BW for 21 days; and PD received PD 300 µg/kg BW for 21 days. LPS-induced immune activation stimulated the HPA axis activation that reflected in enhanced cytokines and hormones level. The proinflammatory plasma cytokines interleukine-6 (IL-6) and tumor necrosis factor-α (TNF-α) level were significantly increased in LPS-challenged mice. The hypothalamic corticotropin-releasing factor (CRF) immunointensity and adrenocorticotrophic hormone (ACTH) and corticosterone level were also substantially increased. After PD treatment, LPS-induced IL-6 and TNF-α, CRF immunoreactivity, ACTH, and corticosterone level were decreased and normalized to control. Thus, the PD modulates the HPA axis activation through anti-inflammatory and psychopharmacological properties.

Key words: Immune activation, hypothalamic-pituitary-adrenal axis, Lipopolysaccharide, Pro-inflammatory cytokines, PD 149163