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Tonic Suppression of the Mesolimbic Dopaminergic System by Enhanced Corticotropin-Releasing Factor Signaling Within the Bed Nucleus of the Stria Terminalis in Chronic Pain Model Rats

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Title: Tonic Suppression of the Mesolimbic Dopaminergic System by Enhanced Corticotropin-Releasing Factor Signaling Within the Bed Nucleus of the Stria Terminalis in Chronic Pain Model Rats
Authors: Takahashi, Daiki Browse this author
Asaoka, Yuta Browse this author
Kimura, Keisuke Browse this author
Hara, Ryuto Browse this author
Arakaki, Saya Browse this author
Sakasai, Keisuke Browse this author
Suzuki, Hiroe Browse this author
Yamauchi, Naoki Browse this author
Nomura, Hiroshi Browse this author
Amano, Taiju Browse this author →KAKEN DB
Minami, Masabumi Browse this author →KAKEN DB
Keywords: bed nucleus of the stria terminalis
corticotropin-releasing factor
dopamine
extended amygdala
pain
ventral tegmental area
Issue Date: 16-Oct-2019
Publisher: Society for Neuroscience
Journal Title: Journal of neuroscience
Volume: 39
Issue: 42
Start Page: 8376
End Page: 8385
Publisher DOI: 10.1523/JNEUROSCI.3047-18.2019
Abstract: Although dysfunction of the mesolimbic dopaminergic system has been implicated in chronic pain, the underlying mechanisms remain to be elucidated. We hypothesized that increased inhibitory inputs to the neuronal pathway from the dorsolateral bed nucleus of the stria terminalis (dIBNST) to the ventral tegmental area (VTA) during chronic pain may induce tonic suppression of the mesolimbic dopaminergic system. To test this hypothesis, male Sprague Dawley rats were subjected to spinal nerve ligation to induce neuropathic pain and then spontaneous IPSCs (sIPSCs) were measured in this neuronal pathway. Whole-cell patch-clamp electrophysiology of brain slices containing the dlBNST revealed that the frequency of sIPSCs significantly increased in VTA-projecting dlBNST neurons 4 weeks after surgery. Next, the role of corticotropin-releasing factor (CRF) signaling within the dlBNST in the increased sIPSCs was examined. CRF increased the frequency of sIPSCs in VTA-projecting dlBNST neurons in sham-operated controls, but not in chronic pain rats. By contrast, NBI27914, a CRF type 1 receptor antagonist, decreased the frequency of sIPSCs in VTA-projecting dlBNST neurons in the chronic pain rats, but not in the control animals. In addition, histological analyses revealed the increased expression of CRF mRNA in the dlBNST. Finally, bilateral injections of NBI27914 into the dlBNST of chronic pain rats activated mesolimbic dopaminergic neurons and induced conditioned place preference. Together, these results suggest that the mesolimbic dopaminergic system is tonically suppressed during chronic pain by enhanced CRF signaling within the dlBNST via increased inhibitory inputs to VTA-projecting dlBNST neurons.
Rights: https://creativecommons.org/licenses/by/4.0/
Type: article
URI: http://hdl.handle.net/2115/77537
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

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