Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in mice
Drug addiction is closely related to the dysregulation of complex neural circuits. However, the specific neural pathways underlying methamphetamine (METH)-induced addiction remain unclear. First, we performed ∆FosB (Delta FBJ murine osteosarcoma viral oncogene homolog B)-mediated immunofluorescence...
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Elsevier
2025-07-01
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| Series: | Brain Research Bulletin |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0361923025002072 |
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| author | Lei Xu Di Zhao Meiqin Wang Lihong Xu Yifan Cao Fantao Meng Jing Liu Zhao Di Wentao Wang Mengdi Zhang Chen Li Shujun Jiang |
| author_facet | Lei Xu Di Zhao Meiqin Wang Lihong Xu Yifan Cao Fantao Meng Jing Liu Zhao Di Wentao Wang Mengdi Zhang Chen Li Shujun Jiang |
| author_sort | Lei Xu |
| collection | DOAJ |
| description | Drug addiction is closely related to the dysregulation of complex neural circuits. However, the specific neural pathways underlying methamphetamine (METH)-induced addiction remain unclear. First, we performed ∆FosB (Delta FBJ murine osteosarcoma viral oncogene homolog B)-mediated immunofluorescence and fiber photometry recording experiments to assess the neural activity of glutamatergic neurons in the insular cortex (IC) in METH-treated mice. Then, we evaluated the effect of activation or inhibition of glutamatergic neurons in IC on METH-induced conditioned place preference (CPP) behavior through chemogenetic manipulations. Finally, we used adeno-associated virus (AAV)-mediated neural tracing to verify the projections connectivity from IC to the basolateral amygdala (BLA), and investigated their blocking role in METH-induced CPP behavior using chemogenetic and neural ablation strategies. We found that glutamatergic neurons in the IC were activated by METH. Activation of these neurons enhanced METH-induced CPP behavior, whereas inhibition of their activity attenuated the CPP expression. Furthermore, we observed robust projections from IC neurons to the BLA. Activation of IC neurons projecting to the BLA enhanced METH-induced CPP behavior, whereas ablation of BLA neurons receiving projections from IC significantly impaired METH-mediated CPP performance. These results highlight the IC glutaminergic neurons are a major target of METH addiction, with the IC-BLA glutamatergic neural projection playing an important role in regulating METH-induced CPP behavior. This pathway may provide new insights into the pathophysiology of METH-induced addiction and serve as a potential target for therapeutic strategies. |
| format | Article |
| id | doaj-art-2b5d9445f4be4c06bfabcb4eb02d7d75 |
| institution | OA Journals |
| issn | 1873-2747 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Research Bulletin |
| spelling | doaj-art-2b5d9445f4be4c06bfabcb4eb02d7d752025-08-20T02:31:33ZengElsevierBrain Research Bulletin1873-27472025-07-0122711139510.1016/j.brainresbull.2025.111395Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in miceLei Xu0Di Zhao1Meiqin Wang2Lihong Xu3Yifan Cao4Fantao Meng5Jing Liu6Zhao Di7Wentao Wang8Mengdi Zhang9Chen Li10Shujun Jiang11Department of Physiology, Binzhou Medical University, Shandong 264003, China; Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaDepartment of Physiology, Binzhou Medical University, Shandong 264003, China; Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, ChinaMedical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Correspondence to: Medical Research Center, Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Binzhou, Shandong 256603, China.Medical Research Center, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Institute for Metabolic & Neuropsychiatric Disorders, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Department of Psychology, Binzhou Medical University Hospital, Binzhou, Shandong 256603, China; Correspondence to: Medical Research Center, Binzhou Medical University Hospital, No. 661 Huanghe 2nd Road, Binzhou, Shandong 256603, China.Department of Physiology, Binzhou Medical University, Shandong 264003, China; Correspondence to: Department of Physiology, Binzhou Medical University, No. 346 Guanhai Road, Yantai, Shandong Province 264003, China.Drug addiction is closely related to the dysregulation of complex neural circuits. However, the specific neural pathways underlying methamphetamine (METH)-induced addiction remain unclear. First, we performed ∆FosB (Delta FBJ murine osteosarcoma viral oncogene homolog B)-mediated immunofluorescence and fiber photometry recording experiments to assess the neural activity of glutamatergic neurons in the insular cortex (IC) in METH-treated mice. Then, we evaluated the effect of activation or inhibition of glutamatergic neurons in IC on METH-induced conditioned place preference (CPP) behavior through chemogenetic manipulations. Finally, we used adeno-associated virus (AAV)-mediated neural tracing to verify the projections connectivity from IC to the basolateral amygdala (BLA), and investigated their blocking role in METH-induced CPP behavior using chemogenetic and neural ablation strategies. We found that glutamatergic neurons in the IC were activated by METH. Activation of these neurons enhanced METH-induced CPP behavior, whereas inhibition of their activity attenuated the CPP expression. Furthermore, we observed robust projections from IC neurons to the BLA. Activation of IC neurons projecting to the BLA enhanced METH-induced CPP behavior, whereas ablation of BLA neurons receiving projections from IC significantly impaired METH-mediated CPP performance. These results highlight the IC glutaminergic neurons are a major target of METH addiction, with the IC-BLA glutamatergic neural projection playing an important role in regulating METH-induced CPP behavior. This pathway may provide new insights into the pathophysiology of METH-induced addiction and serve as a potential target for therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S0361923025002072MethamphetamineConditioned place preference (CPP) behavior, Insular cortex (IC)Basolateral amygdala (BLA)Neuronal projection |
| spellingShingle | Lei Xu Di Zhao Meiqin Wang Lihong Xu Yifan Cao Fantao Meng Jing Liu Zhao Di Wentao Wang Mengdi Zhang Chen Li Shujun Jiang Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in mice Brain Research Bulletin Methamphetamine Conditioned place preference (CPP) behavior, Insular cortex (IC) Basolateral amygdala (BLA) Neuronal projection |
| title | Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in mice |
| title_full | Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in mice |
| title_fullStr | Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in mice |
| title_full_unstemmed | Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in mice |
| title_short | Control of methamphetamine-induced place preference behavior by the glutamatergic neural projections from IC to BLA in mice |
| title_sort | control of methamphetamine induced place preference behavior by the glutamatergic neural projections from ic to bla in mice |
| topic | Methamphetamine Conditioned place preference (CPP) behavior, Insular cortex (IC) Basolateral amygdala (BLA) Neuronal projection |
| url | http://www.sciencedirect.com/science/article/pii/S0361923025002072 |
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