TY - JOUR
T1 - Kappa opioid activation changes protein profiles in different regions of the brain relevant to depression
AU - Varastehmoradi, Bardia
AU - Smith, Karen L
AU - Müller, Heidi Kaastrup
AU - Elfving, Betina
AU - Sanchez, Connie
AU - Wegener, Gregers
N1 - Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2023/7
Y1 - 2023/7
N2 - Depression is a widespread disorder with a significant burden on individuals and society. There are various available treatments for patients with depression. However, not all patients respond adequately to their treatment. Recently, the opioid system has regained interest in depression studies. Research in animals and humans suggest that blocking the kappa opioid receptor (KOR) may potentially alleviate the symptoms of depression. The mechanism behind this effect is not fully understood. Stress and alterations in hypothalamic-pituitary-adrenal axis (HPA-axis) activity are thought to play a crucial role in depression. This study aimed to characterize stress hormones and stress-related protein expression following activation of KOR using a selective agonist. The longitudinal effect was investigated 24 h after KOR activation using the selective agonist U50,488 in Sprague Dawley rats. Stress-related hormones and protein expression patterns were explored using multiplex bead-based assays and western blotting. We found that KOR activation caused an increase in both adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in serum. Regarding protein assays in different brain regions, phosphorylated glucocorticoid receptors also increased significantly in thalamus (THL), hypothalamus (HTH), and striatum (STR). C-Fos increased time-dependently in THL following KOR activation, extracellular signal-regulated kinases 1/2 (ERK1/2) increased significantly in STR and amygdala (AMG), while phosphorylated ERK1/2 decreased during the first 2 h and then increased again in AMG and prefrontal cortex (PFC). This study shows that KOR activation alters the HPA axis and ERK signaling which may cause to develop mood disorders.
AB - Depression is a widespread disorder with a significant burden on individuals and society. There are various available treatments for patients with depression. However, not all patients respond adequately to their treatment. Recently, the opioid system has regained interest in depression studies. Research in animals and humans suggest that blocking the kappa opioid receptor (KOR) may potentially alleviate the symptoms of depression. The mechanism behind this effect is not fully understood. Stress and alterations in hypothalamic-pituitary-adrenal axis (HPA-axis) activity are thought to play a crucial role in depression. This study aimed to characterize stress hormones and stress-related protein expression following activation of KOR using a selective agonist. The longitudinal effect was investigated 24 h after KOR activation using the selective agonist U50,488 in Sprague Dawley rats. Stress-related hormones and protein expression patterns were explored using multiplex bead-based assays and western blotting. We found that KOR activation caused an increase in both adrenocorticotropic hormone (ACTH) and corticosterone (CORT) in serum. Regarding protein assays in different brain regions, phosphorylated glucocorticoid receptors also increased significantly in thalamus (THL), hypothalamus (HTH), and striatum (STR). C-Fos increased time-dependently in THL following KOR activation, extracellular signal-regulated kinases 1/2 (ERK1/2) increased significantly in STR and amygdala (AMG), while phosphorylated ERK1/2 decreased during the first 2 h and then increased again in AMG and prefrontal cortex (PFC). This study shows that KOR activation alters the HPA axis and ERK signaling which may cause to develop mood disorders.
KW - Depression
KW - Opioid receptor
KW - Stress
U2 - 10.1016/j.euroneuro.2023.03.010
DO - 10.1016/j.euroneuro.2023.03.010
M3 - Journal article
C2 - 37040689
SN - 0924-977X
VL - 72
SP - 9
EP - 17
JO - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
JF - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology
ER -