title: Endogenous opioids regulate glucocorticoid-dependent stress-coping strategies in mice.
abstract: Coping skills are essential in determining the outcomes of aversive life events. Our research was aimed to elucidate the molecular underpinnings of different coping styles in two inbred mouse strains, C57BL/6J and SWR/J. We compared the influence of a preceding stressor (0.5h of restraint) on behavioral and gene expression profiles between these two strains. The C57BL/6J strain exhibited increased conditioned fear and high immobility (passive coping). Oppositely, the SWR/J mice demonstrated low freezing and immobility, low post-restraint anxiety and considerable struggling during the forced swim test (active coping). Gene profiling in the amygdala revealed transcriptional patterns that were related to the differential stress reactivity, such as the activation of glucocorticoid-dependent genes specifically in the C57BL/6J mice. Post-restraint blood sampling for corticosterone levels confirmed the association of hypothalamic-pituitary-adrenal (HPA) activation with a passive coping style. Pharmacological tools were used to modulate the stress-coping strategies. The blockade of opioid receptors (ORs) before the aversive event caused transcriptional and neuroendocrine changes in the SWR/J mice that were characteristic of the passive coping strategy. We found that treatment with a glucocorticoid receptor (GR) agonist (dexamethasone (DEX), 4mg/kg) impaired the consolidation of fear memory in the C57BL/6J mice and that this effect was reversed by OR blockade (naltrexone (NTX), 2mg/kg). In parallel, a glucocorticoid receptor antagonist (mifepristone (MIF), 20mg/kg) reversed the effect of morphine (20mg/kg) on conditioned fear in the C57BL/6J mice. Our results suggest that in mice, stress-coping strategies are determined by opioid-dependent mechanisms that modulate activity of the HPA axis.
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland.
authors.forename: Klaudia
authors.initials: K
authors.lastname: Szklarczyk
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland.
authors.forename: Michal
authors.initials: M
authors.lastname: Korostynski
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland.
authors.forename: Slawomir
authors.initials: S
authors.lastname: Golda
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Piechota
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Ficek
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland. Electronic address: nfprzewl@cyf-kr.edu.pl.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Przewlocki
mesh_terms: D000223:Adaptation, Psychological / Q000187:drug effects / Q000502:physiology*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D003863:Depression / Q000188:drug therapy / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology; D005239:Fear / Q000187:drug effects / Q000502:physiology; D046352:Freezing Reaction, Cataleptic / Q000187:drug effects / Q000502:physiology; D005938:Glucocorticoids / Q000378:metabolism*; D008297:Male; D008815:Mice, Inbred Strains / Q000378:metabolism* / Q000523:psychology*; D015735:Mifepristone / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009271:Naltrexone / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology; D018847:Opioid Peptides / Q000378:metabolism*; D011965:Receptors, Glucocorticoid / Q000378:metabolism; D011957:Receptors, Opioid / Q000378:metabolism; D013045:Species Specificity; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D005938:Glucocorticoids; D018377:Neurotransmitter Agents; D018847:Opioid Peptides; D011965:Receptors, Glucocorticoid; D011957:Receptors, Opioid; D015735:Mifepristone; D009271:Naltrexone; D003907:Dexamethasone
keywords: coping; gene expression; glucocorticoids; mice; opioids; stress