Repeated Swim Stress Induces Kappa Opioid-mediated Activation of Extracellular Signal-regulated Kinase 1/2

Overview

Journal Neuroreport

Specialty Neurology

Date 2008 Sep 4

PMID 18766023

Citations 55

Authors

Michael R Bruchas

Mei Xu

Charles Chavkin

Affiliations

Soon will be listed here.

Abstract

Earlier studies identified the dynorphin-kappa opioid receptor (KOR) system as a critical mediator of dysphoria-induced aversion after repeated stress exposure, but the molecular signaling mechanisms were not fully characterized. In this study we report that repeated forced swim stress caused a significant phosphorylation of extracellular signal-regulated kinase (ERK)1/2 a mitogen-activated protein kinase (MAPK) in both the caudate and nucleus accumbens regions of the mouse striatum. Activation was blocked by the KOR antagonist, norbinaltorphimine, and absent in KOR knockout mice. In contrast to p38-MAPK activation by stress-induced dynorphin release, KOR-mediated ERK1/2 phosphorylation was not dependent on G-protein coupled receptor kinase 3 expression. These results indicate stress-induced activation of the dynorphin-KOR systems activates ERK1/2 MAPK signaling, and this may contribute to the behavioral responses to repeated stress exposure.

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References

Ahmed T, Frey J, Korz V . Long-term effects of brief acute stress on cellular signaling and hippocampal LTP. J Neurosci. 2006; 26(15):3951-8. PMC: 6673904. DOI: 10.1523/JNEUROSCI.4901-05.2006. View

Thomas G, Huganir R . MAPK cascade signalling and synaptic plasticity. Nat Rev Neurosci. 2004; 5(3):173-83. DOI: 10.1038/nrn1346. View

Bruchas M, Yang T, Schreiber S, DeFino M, Kwan S, Li S . Long-acting kappa opioid antagonists disrupt receptor signaling and produce noncompetitive effects by activating c-Jun N-terminal kinase. J Biol Chem. 2007; 282(41):29803-11. PMC: 2096775. DOI: 10.1074/jbc.M705540200. View

Carlezon Jr W, Thome J, OLSON V, Brodkin E, Hiroi N, Duman R . Regulation of cocaine reward by CREB. Science. 1998; 282(5397):2272-5. DOI: 10.1126/science.282.5397.2272. View

Bruchas M, Land B, Aita M, Xu M, Barot S, Li S . Stress-induced p38 mitogen-activated protein kinase activation mediates kappa-opioid-dependent dysphoria. J Neurosci. 2007; 27(43):11614-23. PMC: 2481272. DOI: 10.1523/JNEUROSCI.3769-07.2007. View

Porsolt R, Le Pichon M, JALFRE M . Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977; 266(5604):730-2. DOI: 10.1038/266730a0. View

Kreibich A, Blendy J . cAMP response element-binding protein is required for stress but not cocaine-induced reinstatement. J Neurosci. 2004; 24(30):6686-92. PMC: 6729724. DOI: 10.1523/JNEUROSCI.1706-04.2004. View

Shen C, Tsimberg Y, Salvadore C, Meller E . Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions. BMC Neurosci. 2004; 5:36. PMC: 526203. DOI: 10.1186/1471-2202-5-36. View

Kim E, Clark A, Kiss A, Hahn J, Wesselschmidt R, Coscia C . Mu- and kappa-opioids induce the differentiation of embryonic stem cells to neural progenitors. J Biol Chem. 2006; 281(44):33749-60. PMC: 2587057. DOI: 10.1074/jbc.M603862200. View

10.

McLaughlin J, Marton-Popovici M, Chavkin C . Kappa opioid receptor antagonism and prodynorphin gene disruption block stress-induced behavioral responses. J Neurosci. 2003; 23(13):5674-83. PMC: 2104777. View

11.

Mague S, Pliakas A, Todtenkopf M, Tomasiewicz H, Zhang Y, Stevens Jr W . Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats. J Pharmacol Exp Ther. 2003; 305(1):323-30. DOI: 10.1124/jpet.102.046433. View

12.

Shenoy S, Lefkowitz R . Seven-transmembrane receptor signaling through beta-arrestin. Sci STKE. 2005; 2005(308):cm10. DOI: 10.1126/stke.2005/308/cm10. View

13.

Bruchas M, Macey T, Lowe J, Chavkin C . Kappa opioid receptor activation of p38 MAPK is GRK3- and arrestin-dependent in neurons and astrocytes. J Biol Chem. 2006; 281(26):18081-9. PMC: 2096730. DOI: 10.1074/jbc.M513640200. View

14.

Clarke S, Czyzyk T, Ansonoff M, Nitsche J, Hsu M, Nilsson L . Autoradiography of opioid and ORL1 ligands in opioid receptor triple knockout mice. Eur J Neurosci. 2002; 16(9):1705-12. DOI: 10.1046/j.1460-9568.2002.02239.x. View

15.

Beardsley P, Howard J, Shelton K, Carroll F . Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats. Psychopharmacology (Berl). 2005; 183(1):118-26. DOI: 10.1007/s00213-005-0167-4. View

16.

Land B, Bruchas M, Lemos J, Xu M, Melief E, Chavkin C . The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system. J Neurosci. 2008; 28(2):407-14. PMC: 2612708. DOI: 10.1523/JNEUROSCI.4458-07.2008. View

17.

McLaughlin J, Li S, Valdez J, Chavkin T, Chavkin C . Social defeat stress-induced behavioral responses are mediated by the endogenous kappa opioid system. Neuropsychopharmacology. 2005; 31(6):1241-8. PMC: 2096774. DOI: 10.1038/sj.npp.1300872. View

18.

Peppel K, Boekhoff I, McDonald P, Breer H, Caron M, Lefkowitz R . G protein-coupled receptor kinase 3 (GRK3) gene disruption leads to loss of odorant receptor desensitization. J Biol Chem. 1997; 272(41):25425-8. DOI: 10.1074/jbc.272.41.25425. View

19.

Kreek M, Koob G . Drug dependence: stress and dysregulation of brain reward pathways. Drug Alcohol Depend. 1998; 51(1-2):23-47. DOI: 10.1016/s0376-8716(98)00064-7. View

20.

Belcheva M, Clark A, Haas P, Serna J, Hahn J, Kiss A . Mu and kappa opioid receptors activate ERK/MAPK via different protein kinase C isoforms and secondary messengers in astrocytes. J Biol Chem. 2005; 280(30):27662-9. PMC: 1400585. DOI: 10.1074/jbc.M502593200. View