{"title":"通过对成人海马神经发生的多层次刺激,循序渐进的体能和认知训练可破坏可卡因与情境的关联","authors":"","doi":"10.1016/j.pnpbp.2024.111148","DOIUrl":null,"url":null,"abstract":"<div><p>Cocaine-related contextual cues are a recurrent source of craving and relapse. Extinction of cue-driven cocaine seeking remains a clinical challenge, and the search for adjuvants is ongoing. In this regard, combining physical and cognitive training is emerging as a promising strategy that has shown synergistic benefits on brain structure and function, including enhancement of adult hippocampal neurogenesis (AHN), which has been recently linked to reduced maintenance of maladaptive drug seeking. Here, we examined whether this behavioral approach disrupts cocaine-context associations via improved AHN. To this aim, C57BL/6J mice (<em>N</em> = 37) developed a cocaine-induced conditioned place preference (CPP) and underwent interventions consisting of exercise and/or spatial working memory training. Bromodeoxyuridine (BrdU) was administered during early running sessions to tag a subset of new dentate granule cells (DGCs) reaching a critical window of survival during spatial learning. Once these DGCs became functionally mature (∼ 6 weeks-old), mice received extinction training before testing CPP extinction and reinstatement. We found that single and combined treatments accelerated CPP extinction and prevented reinstatement induced by a low cocaine priming (2 mg/kg). Remarkably, the dual-intervention mice showed a significant decrease of CPP after extinction relative to untreated animals. Moreover, combining the two strategies led to increased number and functional integration of BrdU<sup>+</sup> DGCs, which in turn maximized the effect of spatial training (but not exercise) to reduce CPP persistence. Together, our findings suggests that sequencing physical and cognitive training may redound to decreased maintenance of cocaine-context associations, with multi-level stimulation of AHN as a potential underlying mechanism.</p></div>","PeriodicalId":54549,"journal":{"name":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","volume":null,"pages":null},"PeriodicalIF":5.3000,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0278584624002161/pdfft?md5=e82896da4705ab02d2c2fdeccf31f602&pid=1-s2.0-S0278584624002161-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Sequential physical and cognitive training disrupts cocaine-context associations via multi-level stimulation of adult hippocampal neurogenesis\",\"authors\":\"\",\"doi\":\"10.1016/j.pnpbp.2024.111148\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Cocaine-related contextual cues are a recurrent source of craving and relapse. Extinction of cue-driven cocaine seeking remains a clinical challenge, and the search for adjuvants is ongoing. In this regard, combining physical and cognitive training is emerging as a promising strategy that has shown synergistic benefits on brain structure and function, including enhancement of adult hippocampal neurogenesis (AHN), which has been recently linked to reduced maintenance of maladaptive drug seeking. Here, we examined whether this behavioral approach disrupts cocaine-context associations via improved AHN. To this aim, C57BL/6J mice (<em>N</em> = 37) developed a cocaine-induced conditioned place preference (CPP) and underwent interventions consisting of exercise and/or spatial working memory training. Bromodeoxyuridine (BrdU) was administered during early running sessions to tag a subset of new dentate granule cells (DGCs) reaching a critical window of survival during spatial learning. Once these DGCs became functionally mature (∼ 6 weeks-old), mice received extinction training before testing CPP extinction and reinstatement. We found that single and combined treatments accelerated CPP extinction and prevented reinstatement induced by a low cocaine priming (2 mg/kg). Remarkably, the dual-intervention mice showed a significant decrease of CPP after extinction relative to untreated animals. Moreover, combining the two strategies led to increased number and functional integration of BrdU<sup>+</sup> DGCs, which in turn maximized the effect of spatial training (but not exercise) to reduce CPP persistence. Together, our findings suggests that sequencing physical and cognitive training may redound to decreased maintenance of cocaine-context associations, with multi-level stimulation of AHN as a potential underlying mechanism.</p></div>\",\"PeriodicalId\":54549,\"journal\":{\"name\":\"Progress in Neuro-Psychopharmacology & Biological Psychiatry\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2024-09-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0278584624002161/pdfft?md5=e82896da4705ab02d2c2fdeccf31f602&pid=1-s2.0-S0278584624002161-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Progress in Neuro-Psychopharmacology & Biological Psychiatry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0278584624002161\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Progress in Neuro-Psychopharmacology & Biological Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278584624002161","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Sequential physical and cognitive training disrupts cocaine-context associations via multi-level stimulation of adult hippocampal neurogenesis
Cocaine-related contextual cues are a recurrent source of craving and relapse. Extinction of cue-driven cocaine seeking remains a clinical challenge, and the search for adjuvants is ongoing. In this regard, combining physical and cognitive training is emerging as a promising strategy that has shown synergistic benefits on brain structure and function, including enhancement of adult hippocampal neurogenesis (AHN), which has been recently linked to reduced maintenance of maladaptive drug seeking. Here, we examined whether this behavioral approach disrupts cocaine-context associations via improved AHN. To this aim, C57BL/6J mice (N = 37) developed a cocaine-induced conditioned place preference (CPP) and underwent interventions consisting of exercise and/or spatial working memory training. Bromodeoxyuridine (BrdU) was administered during early running sessions to tag a subset of new dentate granule cells (DGCs) reaching a critical window of survival during spatial learning. Once these DGCs became functionally mature (∼ 6 weeks-old), mice received extinction training before testing CPP extinction and reinstatement. We found that single and combined treatments accelerated CPP extinction and prevented reinstatement induced by a low cocaine priming (2 mg/kg). Remarkably, the dual-intervention mice showed a significant decrease of CPP after extinction relative to untreated animals. Moreover, combining the two strategies led to increased number and functional integration of BrdU+ DGCs, which in turn maximized the effect of spatial training (but not exercise) to reduce CPP persistence. Together, our findings suggests that sequencing physical and cognitive training may redound to decreased maintenance of cocaine-context associations, with multi-level stimulation of AHN as a potential underlying mechanism.
期刊介绍:
Progress in Neuro-Psychopharmacology & Biological Psychiatry is an international and multidisciplinary journal which aims to ensure the rapid publication of authoritative reviews and research papers dealing with experimental and clinical aspects of neuro-psychopharmacology and biological psychiatry. Issues of the journal are regularly devoted wholly in or in part to a topical subject.
Progress in Neuro-Psychopharmacology & Biological Psychiatry does not publish work on the actions of biological extracts unless the pharmacological active molecular substrate and/or specific receptor binding properties of the extract compounds are elucidated.