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

Takahashi, Daiki; Asaoka, Yuta; Kimura, Keisuke; Hara, Ryuto; Arakaki, Saya; Sakasai, Keisuke; Suzuki, Hiroe; Yamauchi, Naoki; Nomura, Hiroshi; Amano, Taiju; Minami, Masabumi

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

Takahashi, Daiki; Asaoka, Yuta; Kimura, Keisuke et al.

Journal of neuroscience, 2019, 39(42), 8376-8385

Permalink : https://hdl.handle.net/2115/77537

このアイテムのアクセス数:613件（2026-10-12 08:21 集計）

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https://doi.org/10.1523/JNEUROSCI.3047-18.2019			27

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アクセス権	open access
URI	https://hdl.handle.net/2115/77537
タイトル	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
著者	Takahashi, Daiki ; Asaoka, Yuta ; Kimura, Keisuke ; Hara, Ryuto ; Arakaki, Saya ; Sakasai, Keisuke ; Suzuki, Hiroe ; Yamauchi, Naoki ; Nomura, Hiroshi ; Amano, Taiju ; Minami, Masabumi
著者名 Takahashi, Daiki
著者名 Asaoka, Yuta
著者名 Kimura, Keisuke
著者名 Hara, Ryuto
著者名 Arakaki, Saya
著者名 Sakasai, Keisuke
著者名 Suzuki, Hiroe
著者名 Yamauchi, Naoki
著者名 Nomura, Hiroshi
e-Rad_Researcher 00591950 著者名 Amano, Taiju
e-Rad_Researcher 20243040 著者名 Minami, Masabumi
言語	英語
キーワード	bed nucleus of the stria terminalis
	corticotropin-releasing factor
	dopamine
	extended amygdala
	pain
	ventral tegmental area
発行日	2019-10-16
出版者	Society for Neuroscience
収録物名	Journal of neuroscience
巻(号)	39(42)
ページ	8376-8385
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
権利情報	Creative Commons Attribution 4.0 International
PISSN	0270-6474
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.1523/JNEUROSCI.3047-18.2019