Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats

Allison T. Knoll, John W. Muschamp, Stephanie E. Sillivan, Deveroux Ferguson, David M. Dietz, Edward G. Meloni, F. Ivy Carroll, Eric J. Nestler, Christine Konradi, William A. Carlezon

Research output: Contribution to journalArticle

82 Citations (Scopus)

Abstract

Background: The kappa opioid receptor (KOR) system contributes to the prodepressive and aversive consequences of stress and is implicated in the facilitation of conditioned fear and anxiety in rodents. Here, we sought to identify neural circuits that mediate KOR system effects on fear and anxiety in rats. Methods: We assessed whether fear conditioning induces plasticity in KOR or dynorphin (the endogenous KOR ligand) messenger RNA (mRNA) expression in the basolateral (BLA) and central (CeA) nuclei of the amygdala, hippocampus, or striatum. We then assessed whether microinfusions of the KOR antagonist JDTic (010 μg/side) into the BLA or CeA affect the expression of conditioned fear or anxiety. Finally, we examined whether fear extinction induces plasticity in KOR mRNA expression that relates to the quality of fear extinction. Results: Fear conditioning upregulated KOR mRNA in the BLA by 65% and downregulated it in the striatum by 22%, without affecting KOR levels in the CeA or hippocampus, or dynorphin levels in any region. KOR antagonism in either the BLA or CeA decreased conditioned fear in the fear-potentiated startle paradigm, whereas KOR antagonism in the BLA, but not the CeA, produced anxiolytic-like effects in the elevated plus maze. Effective fear extinction was associated with a 67% reduction in KOR mRNA in the BLA. Conclusions: These findings suggest that fear conditioning and extinction dynamically regulate KOR expression in the BLA and provide evidence that the BLA and CeA are important neural substrates mediating the anxiolytic-like effects of KOR antagonists in models of fear and anxiety.

Original languageEnglish (US)
Pages (from-to)425-433
Number of pages9
JournalBiological Psychiatry
Volume70
Issue number5
DOIs
StatePublished - Sep 1 2011
Externally publishedYes

Fingerprint

kappa Opioid Receptor
Fear
Anxiety
Dynorphins
Messenger RNA
Narcotic Antagonists
Anti-Anxiety Agents
Basolateral Nuclear Complex
Hippocampus
Rodentia

Keywords

  • Anxiety
  • conditioned fear
  • elevated plus maze
  • fear-potentiated startle
  • JDTic
  • quantitative PCR

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Knoll, A. T., Muschamp, J. W., Sillivan, S. E., Ferguson, D., Dietz, D. M., Meloni, E. G., ... Carlezon, W. A. (2011). Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats. Biological Psychiatry, 70(5), 425-433. https://doi.org/10.1016/j.biopsych.2011.03.017

Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats. / Knoll, Allison T.; Muschamp, John W.; Sillivan, Stephanie E.; Ferguson, Deveroux; Dietz, David M.; Meloni, Edward G.; Carroll, F. Ivy; Nestler, Eric J.; Konradi, Christine; Carlezon, William A.

In: Biological Psychiatry, Vol. 70, No. 5, 01.09.2011, p. 425-433.

Research output: Contribution to journalArticle

Knoll, AT, Muschamp, JW, Sillivan, SE, Ferguson, D, Dietz, DM, Meloni, EG, Carroll, FI, Nestler, EJ, Konradi, C & Carlezon, WA 2011, 'Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats', Biological Psychiatry, vol. 70, no. 5, pp. 425-433. https://doi.org/10.1016/j.biopsych.2011.03.017
Knoll, Allison T. ; Muschamp, John W. ; Sillivan, Stephanie E. ; Ferguson, Deveroux ; Dietz, David M. ; Meloni, Edward G. ; Carroll, F. Ivy ; Nestler, Eric J. ; Konradi, Christine ; Carlezon, William A. / Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats. In: Biological Psychiatry. 2011 ; Vol. 70, No. 5. pp. 425-433.
@article{9086035f4bf94ddca455b2e658eb0185,
title = "Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats",
abstract = "Background: The kappa opioid receptor (KOR) system contributes to the prodepressive and aversive consequences of stress and is implicated in the facilitation of conditioned fear and anxiety in rodents. Here, we sought to identify neural circuits that mediate KOR system effects on fear and anxiety in rats. Methods: We assessed whether fear conditioning induces plasticity in KOR or dynorphin (the endogenous KOR ligand) messenger RNA (mRNA) expression in the basolateral (BLA) and central (CeA) nuclei of the amygdala, hippocampus, or striatum. We then assessed whether microinfusions of the KOR antagonist JDTic (010 μg/side) into the BLA or CeA affect the expression of conditioned fear or anxiety. Finally, we examined whether fear extinction induces plasticity in KOR mRNA expression that relates to the quality of fear extinction. Results: Fear conditioning upregulated KOR mRNA in the BLA by 65{\%} and downregulated it in the striatum by 22{\%}, without affecting KOR levels in the CeA or hippocampus, or dynorphin levels in any region. KOR antagonism in either the BLA or CeA decreased conditioned fear in the fear-potentiated startle paradigm, whereas KOR antagonism in the BLA, but not the CeA, produced anxiolytic-like effects in the elevated plus maze. Effective fear extinction was associated with a 67{\%} reduction in KOR mRNA in the BLA. Conclusions: These findings suggest that fear conditioning and extinction dynamically regulate KOR expression in the BLA and provide evidence that the BLA and CeA are important neural substrates mediating the anxiolytic-like effects of KOR antagonists in models of fear and anxiety.",
keywords = "Anxiety, conditioned fear, elevated plus maze, fear-potentiated startle, JDTic, quantitative PCR",
author = "Knoll, {Allison T.} and Muschamp, {John W.} and Sillivan, {Stephanie E.} and Deveroux Ferguson and Dietz, {David M.} and Meloni, {Edward G.} and Carroll, {F. Ivy} and Nestler, {Eric J.} and Christine Konradi and Carlezon, {William A.}",
year = "2011",
month = "9",
day = "1",
doi = "10.1016/j.biopsych.2011.03.017",
language = "English (US)",
volume = "70",
pages = "425--433",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "5",

}

TY - JOUR

T1 - Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats

AU - Knoll, Allison T.

AU - Muschamp, John W.

AU - Sillivan, Stephanie E.

AU - Ferguson, Deveroux

AU - Dietz, David M.

AU - Meloni, Edward G.

AU - Carroll, F. Ivy

AU - Nestler, Eric J.

AU - Konradi, Christine

AU - Carlezon, William A.

PY - 2011/9/1

Y1 - 2011/9/1

N2 - Background: The kappa opioid receptor (KOR) system contributes to the prodepressive and aversive consequences of stress and is implicated in the facilitation of conditioned fear and anxiety in rodents. Here, we sought to identify neural circuits that mediate KOR system effects on fear and anxiety in rats. Methods: We assessed whether fear conditioning induces plasticity in KOR or dynorphin (the endogenous KOR ligand) messenger RNA (mRNA) expression in the basolateral (BLA) and central (CeA) nuclei of the amygdala, hippocampus, or striatum. We then assessed whether microinfusions of the KOR antagonist JDTic (010 μg/side) into the BLA or CeA affect the expression of conditioned fear or anxiety. Finally, we examined whether fear extinction induces plasticity in KOR mRNA expression that relates to the quality of fear extinction. Results: Fear conditioning upregulated KOR mRNA in the BLA by 65% and downregulated it in the striatum by 22%, without affecting KOR levels in the CeA or hippocampus, or dynorphin levels in any region. KOR antagonism in either the BLA or CeA decreased conditioned fear in the fear-potentiated startle paradigm, whereas KOR antagonism in the BLA, but not the CeA, produced anxiolytic-like effects in the elevated plus maze. Effective fear extinction was associated with a 67% reduction in KOR mRNA in the BLA. Conclusions: These findings suggest that fear conditioning and extinction dynamically regulate KOR expression in the BLA and provide evidence that the BLA and CeA are important neural substrates mediating the anxiolytic-like effects of KOR antagonists in models of fear and anxiety.

AB - Background: The kappa opioid receptor (KOR) system contributes to the prodepressive and aversive consequences of stress and is implicated in the facilitation of conditioned fear and anxiety in rodents. Here, we sought to identify neural circuits that mediate KOR system effects on fear and anxiety in rats. Methods: We assessed whether fear conditioning induces plasticity in KOR or dynorphin (the endogenous KOR ligand) messenger RNA (mRNA) expression in the basolateral (BLA) and central (CeA) nuclei of the amygdala, hippocampus, or striatum. We then assessed whether microinfusions of the KOR antagonist JDTic (010 μg/side) into the BLA or CeA affect the expression of conditioned fear or anxiety. Finally, we examined whether fear extinction induces plasticity in KOR mRNA expression that relates to the quality of fear extinction. Results: Fear conditioning upregulated KOR mRNA in the BLA by 65% and downregulated it in the striatum by 22%, without affecting KOR levels in the CeA or hippocampus, or dynorphin levels in any region. KOR antagonism in either the BLA or CeA decreased conditioned fear in the fear-potentiated startle paradigm, whereas KOR antagonism in the BLA, but not the CeA, produced anxiolytic-like effects in the elevated plus maze. Effective fear extinction was associated with a 67% reduction in KOR mRNA in the BLA. Conclusions: These findings suggest that fear conditioning and extinction dynamically regulate KOR expression in the BLA and provide evidence that the BLA and CeA are important neural substrates mediating the anxiolytic-like effects of KOR antagonists in models of fear and anxiety.

KW - Anxiety

KW - conditioned fear

KW - elevated plus maze

KW - fear-potentiated startle

KW - JDTic

KW - quantitative PCR

UR - http://www.scopus.com/inward/record.url?scp=80051472538&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80051472538&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2011.03.017

DO - 10.1016/j.biopsych.2011.03.017

M3 - Article

VL - 70

SP - 425

EP - 433

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 5

ER -