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Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats.
Biol Psychiatry. 2011 Sep 01; 70(5):425-33.BP

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 (0-10 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.

Authors+Show Affiliations

Department of Psychiatry, Behavioral Genetics Laboratory, Harvard Medical School, McLean Hospital, Belmont, Massachusetts, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

21531393

Citation

Knoll, Allison T., et al. "Kappa Opioid Receptor Signaling in the Basolateral Amygdala Regulates Conditioned Fear and Anxiety in Rats." Biological Psychiatry, vol. 70, no. 5, 2011, pp. 425-33.
Knoll AT, Muschamp JW, Sillivan SE, et al. Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats. Biol Psychiatry. 2011;70(5):425-33.
Knoll, A. T., Muschamp, J. W., Sillivan, S. E., Ferguson, D., Dietz, D. M., Meloni, E. G., Carroll, F. I., Nestler, E. J., Konradi, C., & Carlezon, W. A. (2011). Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats. Biological Psychiatry, 70(5), 425-33. https://doi.org/10.1016/j.biopsych.2011.03.017
Knoll AT, et al. Kappa Opioid Receptor Signaling in the Basolateral Amygdala Regulates Conditioned Fear and Anxiety in Rats. Biol Psychiatry. 2011 Sep 1;70(5):425-33. PubMed PMID: 21531393.
* Article titles in AMA citation format should be in sentence-case
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,Jr Y1 - 2011/04/30/ PY - 2011/01/26/received PY - 2011/03/07/revised PY - 2011/03/10/accepted PY - 2011/5/3/entrez PY - 2011/5/3/pubmed PY - 2011/12/13/medline SP - 425 EP - 33 JF - Biological psychiatry JO - Biol. Psychiatry VL - 70 IS - 5 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 (0-10 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. SN - 1873-2402 UR - https://www.unboundmedicine.com/medline/citation/21531393/Kappa_opioid_receptor_signaling_in_the_basolateral_amygdala_regulates_conditioned_fear_and_anxiety_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-3223(11)00261-7 DB - PRIME DP - Unbound Medicine ER -