The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats
Many studies in humans and rodents have shown that the anterior cingulate cortex (ACC) plays a critical role in the regulation of pain-related aversion and that the projection from the rostral ACC (rACC) to the ventral tegmental area (VTA) is implicated in this modulation process. The ACC is also re...
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Elsevier
2025-04-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996125000609 |
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| author | Jun-Fei Teng Xing-Yu Lu Jun-Hui Long Ying Shi Xue-Qiang Hu Jian-Feng Sui Ping Wang Lian-Lin Zeng Xuan Li Jin-He Xu Zu-Zhen Ou Ke-Hui Hu Shu-Lei Liu |
| author_facet | Jun-Fei Teng Xing-Yu Lu Jun-Hui Long Ying Shi Xue-Qiang Hu Jian-Feng Sui Ping Wang Lian-Lin Zeng Xuan Li Jin-He Xu Zu-Zhen Ou Ke-Hui Hu Shu-Lei Liu |
| author_sort | Jun-Fei Teng |
| collection | DOAJ |
| description | Many studies in humans and rodents have shown that the anterior cingulate cortex (ACC) plays a critical role in the regulation of pain-related aversion and that the projection from the rostral ACC (rACC) to the ventral tegmental area (VTA) is implicated in this modulation process. The ACC is also reported to be involved in the regulation of itch-scratch behavior. However, it remains unclear whether the ACC is involved in the modulation of the negative emotions induced by acute itch sensation. In this study, we investigated the pruritogen-induced conditioned place aversion (CPA) and itch-scratching behavior in rats after pharmacogenetic inhibition of the activities of rACC-VTA pathway or the rACC neurons, respectively. Pharmacogenetic inhibition of glutamatergic neurons of rACC projecting to the VTA alleviated the CPA responses and itch-scratching behavior induced by the subcutaneous injection of 5-HT, a nonhistamine-dependent pruritogen. However, pharmacogenetic inhibition of rACC neurons did not change the CPA behavior associated with itch and, conversely, increased itch-scratching behavior. These results reveal that a specific subpopulation of rACC neurons projecting to the VTA positively regulates itch sensation and the negative emotion accompanying itch, whereas the global rACC negatively modulates acute non-histaminergic itch in rats. Postsynaptic GABAergic neurons in the VTA may mediate emotion modulation of the rACC-VTA pathway. The current findings contribute to a better understanding of the circuit mechanisms underlying the processing of different components of itch, such as sensation and emotion. |
| format | Article |
| id | doaj-art-0302ec4df4e046edad777df79880d3fb |
| institution | DOAJ |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-0302ec4df4e046edad777df79880d3fb2025-08-20T02:55:46ZengElsevierNeurobiology of Disease1095-953X2025-04-0120710684410.1016/j.nbd.2025.106844The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in ratsJun-Fei Teng0Xing-Yu Lu1Jun-Hui Long2Ying Shi3Xue-Qiang Hu4Jian-Feng Sui5Ping Wang6Lian-Lin Zeng7Xuan Li8Jin-He Xu9Zu-Zhen Ou10Ke-Hui Hu11Shu-Lei Liu12Department of Dermatology of Jiangbei Campus, The First Affiliated Hospital of Army Medical University, Chongqing 400020, ChinaDepartment of Dermatology of Jiangbei Campus, The First Affiliated Hospital of Army Medical University, Chongqing 400020, ChinaDepartment of Dermatology of Jiangbei Campus, The First Affiliated Hospital of Army Medical University, Chongqing 400020, ChinaDepartment of Rheumatology, The Ninth People's Hospital of Chongqing, Chongqing 400799, ChinaDepartment of Dermatology of Jiangbei Campus, The First Affiliated Hospital of Army Medical University, Chongqing 400020, ChinaDepartment of Rehabilitation Medicine, SuiNing Central Hospital, SuiNing 629000, China; Experimental Center of Basic Medicine, Army Medical University, Chongqing 400038, ChinaDepartment of Dermatology of Jiangbei Campus, The First Affiliated Hospital of Army Medical University, Chongqing 400020, ChinaDepartment of Rehabilitation Medicine, SuiNing Central Hospital, SuiNing 629000, ChinaExperimental Center of Basic Medicine, Army Medical University, Chongqing 400038, ChinaExperimental Center of Basic Medicine, Army Medical University, Chongqing 400038, ChinaDepartment of Dermatology of Jiangbei Campus, The First Affiliated Hospital of Army Medical University, Chongqing 400020, ChinaDepartment of Rehabilitation Medicine, SuiNing Central Hospital, SuiNing 629000, China; Corresponding authors.Department of Dermatology of Jiangbei Campus, The First Affiliated Hospital of Army Medical University, Chongqing 400020, China; Corresponding authors.Many studies in humans and rodents have shown that the anterior cingulate cortex (ACC) plays a critical role in the regulation of pain-related aversion and that the projection from the rostral ACC (rACC) to the ventral tegmental area (VTA) is implicated in this modulation process. The ACC is also reported to be involved in the regulation of itch-scratch behavior. However, it remains unclear whether the ACC is involved in the modulation of the negative emotions induced by acute itch sensation. In this study, we investigated the pruritogen-induced conditioned place aversion (CPA) and itch-scratching behavior in rats after pharmacogenetic inhibition of the activities of rACC-VTA pathway or the rACC neurons, respectively. Pharmacogenetic inhibition of glutamatergic neurons of rACC projecting to the VTA alleviated the CPA responses and itch-scratching behavior induced by the subcutaneous injection of 5-HT, a nonhistamine-dependent pruritogen. However, pharmacogenetic inhibition of rACC neurons did not change the CPA behavior associated with itch and, conversely, increased itch-scratching behavior. These results reveal that a specific subpopulation of rACC neurons projecting to the VTA positively regulates itch sensation and the negative emotion accompanying itch, whereas the global rACC negatively modulates acute non-histaminergic itch in rats. Postsynaptic GABAergic neurons in the VTA may mediate emotion modulation of the rACC-VTA pathway. The current findings contribute to a better understanding of the circuit mechanisms underlying the processing of different components of itch, such as sensation and emotion.http://www.sciencedirect.com/science/article/pii/S0969996125000609ItchCingulate cortexVentral tegmental areaAversionRats |
| spellingShingle | Jun-Fei Teng Xing-Yu Lu Jun-Hui Long Ying Shi Xue-Qiang Hu Jian-Feng Sui Ping Wang Lian-Lin Zeng Xuan Li Jin-He Xu Zu-Zhen Ou Ke-Hui Hu Shu-Lei Liu The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats Neurobiology of Disease Itch Cingulate cortex Ventral tegmental area Aversion Rats |
| title | The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats |
| title_full | The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats |
| title_fullStr | The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats |
| title_full_unstemmed | The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats |
| title_short | The projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5-HT-induced itch aversion and scratching in rats |
| title_sort | projection from the rostral anterior cingulate cortex to the ventral tegmental area regulates 5 ht induced itch aversion and scratching in rats |
| topic | Itch Cingulate cortex Ventral tegmental area Aversion Rats |
| url | http://www.sciencedirect.com/science/article/pii/S0969996125000609 |
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