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Amygdala Metabotropic Glutamate Receptor 1 Influences Synaptic Transmission to Participate in Fentanyl-Induced Hyperalgesia in Rats

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Abstract

The underlying mechanisms of opioid-induced hyperalgesia (OIH) remain unclear. Herein, we found that the protein expression of metabotropic glutamate receptor 1 (mGluR1) was significantly increased in the right but not in the left laterocapsular division of central nucleus of the amygdala (CeLC) in OIH rats. In CeLC neurons, the frequency and the amplitude of mini-excitatory postsynaptic currents (mEPSCs) were significantly increased in fentanyl group which were decreased by acute application of a mGluR1 antagonist, A841720. Finally, the behavioral hypersensitivity could be reversed by A841720 microinjection into the right CeLC. These results show that the right CeLC mGluR1 is an important factor associated with OIH that enhances synaptic transmission and could be a potential drug target to alleviate fentanyl-induced hyperalgesia.

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The authors acknowledge that the data presented in this study must be deposited and made publicly available in an acceptable repository, prior to publication.

Abbreviations

OIH:

Opioid-induced hyperalgesia

mGluR:

Metabotropic glutamate receptor

CeLC:

Laterocapsular division of central nucleus of the amygdala

mEPSCs:

Mini-excitatory postsynaptic currents

ERK:

Extracellular signal-regulated kinase (ERK)

NMDA:

N-Methyl-d-aspartate

iGluR:

Ionotropic glutamate receptor

ACSF:

Artificial cerebrospinal fluid

RVM:

Rostroventral medulla of the brainstem

LA/BLA:

Lateral/basolateral amygdala nuclei

ITC:

Intercalated cell mass of the amygdala

CeA:

Central nucleus of the amygdala

mPFC:

Medial prefrontal cortex

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Funding

This work was supported by the National Natural Science Foundation of China (grant nos. 31870771, 31500996, 3212018, 81271234, 81771196), National Science Foundation of Hubei (2020CFA025), the Fundamental Research Funds for the Central Universities, South-Central MinZu University (CZY17030, CZY18027, CZY19023, CZQ20004), and Hubei Key Laboratory of Medical Information Analysis and Tumor Diagnosis & Treatment (PJS140011610).

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Contributions

CL, HC, and TB designed the study; HC, TB, WH, and JL implemented the experiments; HC, XL, SC, FL, and XY analyzed data; TB, HC, and CL drafted the paper. TB and HC contributed equally to this work.

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Correspondence to Chenhong Li.

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The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Bai, T., Chen, H., Hu, W. et al. Amygdala Metabotropic Glutamate Receptor 1 Influences Synaptic Transmission to Participate in Fentanyl-Induced Hyperalgesia in Rats. Cell Mol Neurobiol 43, 1401–1412 (2023). https://doi.org/10.1007/s10571-022-01248-x

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  • DOI: https://doi.org/10.1007/s10571-022-01248-x

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