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Aversive Stress Reduces Mu Opioid Receptor Expression in the Intercalated Nuclei of the Rat Amygdala

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Abstract

The amygdala plays an important role in the integration of responses to noxious and fearful stimuli. Sensory information from many systems is integrated in the lateral and basolateral amygdala and transmitted to the central amygdala, the major output nucleus of the amygdala regulating both motor and emotional responses. The network of intercalated cells (ITC) which surrounds the lateral and basolateral amygdala and serves to modulate information flow from the lateral amygdala to the central nucleus, express a very high local concentration of mu-type opioid receptors. Loss of the ITC neurons impairs fear extinction. We demonstrate here that exposure of rats to a severe stress experience resulted in a marked downregulation of the level of expression of mu opioid receptors in the ITC nuclei over a period of at least 24 h after the end of the stress exposure. The endogenous opioid dynorphin is also expressed in the central and ITC nuclei of the amygdala. Following stress exposure, we also observed an increase in the expression in the more lateral regions of the central amygdala of pro-dynorphin mRNA and a peptide product of pro-dynorphin with known affinity for mu opioid receptors. It is possible that the downregulation of mu receptors in ITC neurons after stress may result from sustained activation and internalization of mu receptors following a stress-induced increase in the release of endogenous opioid peptides.

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Acknowledgments

We thank Dr. He Li, Department of Psychiatry, Uniformed Services University, for use of equipment and for helpful advice and discussion and Dr. E. Weber for gift of the antiserum for Dynorphin A(1-8).

Funding

This work was supported by USAMRMC Research Grant #W81XWH 0820575. The research was reviewed and approved by the Uniformed Services University Animal Care and Use Committee (IACUC) in accordance with all applicable Federal regulations governing the protection of animals in research.

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  1. Department of Pharmacology & Molecular Therapeutics, Uniformed Services University, Bethesda, MD, 20814, USA

    Shawn Gouty, Julia Tomoyasu Silveira, Thomas E. Cote & Brian M. Cox

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  1. Shawn Gouty
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  2. Julia Tomoyasu Silveira
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  3. Thomas E. Cote
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  4. Brian M. Cox
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Correspondence to Brian M. Cox.

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Gouty, S., Silveira, J.T., Cote, T.E. et al. Aversive Stress Reduces Mu Opioid Receptor Expression in the Intercalated Nuclei of the Rat Amygdala. Cell Mol Neurobiol 41, 1119–1129 (2021). https://doi.org/10.1007/s10571-020-01026-7

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  • DOI: https://doi.org/10.1007/s10571-020-01026-7

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