title: Opioid-dependent regulation of high and low fear responses in two inbred mouse strains.
abstract: The molecular mechanisms underlying the susceptibility or resilience to trauma-related disorders remain incompletely understood. Opioids modulate emotional learning, but the roles of specific receptors are unclear. Here, we aimed to analyze the contribution of the opioid system to fear responses in two inbred mouse strains exhibiting distinct behavioral phenotypes. SWR/J and C57BL/6J mice were subjected to five consecutive electric footshocks (1mA each), and the contextual freezing time was measured. Stress-induced alterations in gene expression were analyzed in the amygdala and the hippocampus. In both strains, the fear response was modulated using pharmacological tools. SWR/J mice did not develop conditioned fear but exhibited increased transcriptional expression of Pdyn and Penk in the amygdala region. Blocking opioid receptors prior to the footshocks using naltrexone (2 mg/kg) or naltrindole (5 mg/kg) increased the freezing responses in these animals. The C57BL/6J strain displayed high conditioned fear, although no alteration in the mRNA abundance of genes encoding opioid precursors was observed. Double-injection of morphine (20 mg/kg) following stress and upon context re-exposure prevented the enhancement of freezing. Moreover, selective delta and kappa agonists caused a reduction in conditioned fear responses. To summarize, the increased expression of the Pdyn and Penk genes corresponded to reduced intensity of fear responses. Blockade of the endogenous opioid system restored freezing behavior in stress-resistant animals. The pharmacological stimulation of the kappa and delta opioid receptors in stress-susceptible individuals may alleviate fear. Thus, subtype-selective opioid receptor agonists may protect against the development of trauma-related disorders.
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; Institute of Applied Psychology, Jagiellonian University, Krakow, Poland.
authors.forename: Przemyslaw Eligiusz
authors.initials: PE
authors.lastname: Cieslak
authors.affiliation: Department of Molecular Neuropharmacology, Institute of Pharmacology PAS, Krakow, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Wawrzczak-Bargiela
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: D000679:Amygdala / Q000187:drug effects / Q000502:physiology; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003214:Conditioning, Classical; D004745:Enkephalins / Q000096:biosynthesis / Q000235:genetics; D005239:Fear / Q000187:drug effects* / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D056726:Genetic Association Studies; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D011957:Receptors, Opioid / Q000819:agonists; D013315:Stress, Psychological / Q000235:genetics / Q000523:psychology
chemical_list: D000701:Analgesics, Opioid; D004745:Enkephalins; D011498:Protein Precursors; D011957:Receptors, Opioid; D009271:Naltrexone; C033660:preproenkephalin; C055382:naltrindole
keywords: Amygdala; Animal models; Delta receptor; Fear conditioning; Opioids; Posttraumatic stress disorder