Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies
Abstract Substance Use Disorder (SUD) is a medical condition where an individual compulsively misuses drugs or alcohol despite knowing the negative consequences. The anterior cingulate cortex (ACC) has been implicated in various types of SUDs, including nicotine, heroin, and alcohol use disorders. O...
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Nature Portfolio
2025-01-01
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| author | Mahdi Fatemizadeh Esmail Riahi Gholamreza Hassanzadeh Anahita Torkaman-Boutorabi Forough Radfar Maryam Farahmandfar |
| author_facet | Mahdi Fatemizadeh Esmail Riahi Gholamreza Hassanzadeh Anahita Torkaman-Boutorabi Forough Radfar Maryam Farahmandfar |
| author_sort | Mahdi Fatemizadeh |
| collection | DOAJ |
| description | Abstract Substance Use Disorder (SUD) is a medical condition where an individual compulsively misuses drugs or alcohol despite knowing the negative consequences. The anterior cingulate cortex (ACC) has been implicated in various types of SUDs, including nicotine, heroin, and alcohol use disorders. Our research aimed to investigate the effects of deep brain stimulation (DBS) in the ACC as a potential therapeutic approach for morphine use disorder. Additionally, we measured c-Fos protein expression as an indicator of neural activity in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Our findings indicate that high-frequency (130 Hz) DBS at different amperages, 150 µA and 200 µA in the ACC during the acquisition phase of morphine conditioned place preference (CPP) inhibited the rewarding properties of morphine. Furthermore, DBS at these intensities during the extinction phase facilitated the extinction and mitigated the reinstatement of morphine CPP triggered by drug priming. Morphine conditioning was associated with impaired novel object conditioning (NOR) and locomotor activity. While DBS in the acquisition and extinction phases at both intensities restored NOR memory, only DBS at 200 µA recovered locomotor activity in the open field test. Treatment with DBS at 200 µA decreased c-Fos protein expression in the NAc and PFC (compared to morphine-only group). In conclusion, our data indicate an intensity-dependent effect of ACC DBS on the acquisition, extinction, and reinstatement of morphine-induced CPP in rats. These findings suggest that ACC DBS could be a potential intervention for the treatment of morphine use disorder. |
| format | Article |
| id | doaj-art-115702d9f0a849aea9fc38d518c71584 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-115702d9f0a849aea9fc38d518c715842025-01-19T12:17:11ZengNature PortfolioScientific Reports2045-23222025-01-0115111310.1038/s41598-025-86279-2Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studiesMahdi Fatemizadeh0Esmail Riahi1Gholamreza Hassanzadeh2Anahita Torkaman-Boutorabi3Forough Radfar4Maryam Farahmandfar5Department of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesDepartment of Physiology, School of Medicine, Tehran University of Medical SciencesDepartment of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesDepartment of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesDepartment of Behavioral and Cognitive Sciences in Sports, Sports and Health Sciences Faculty, University of TehranDepartment of Neuroscience and Addiction Studies, School of Advanced Technologies in Medicine, Tehran University of Medical SciencesAbstract Substance Use Disorder (SUD) is a medical condition where an individual compulsively misuses drugs or alcohol despite knowing the negative consequences. The anterior cingulate cortex (ACC) has been implicated in various types of SUDs, including nicotine, heroin, and alcohol use disorders. Our research aimed to investigate the effects of deep brain stimulation (DBS) in the ACC as a potential therapeutic approach for morphine use disorder. Additionally, we measured c-Fos protein expression as an indicator of neural activity in the nucleus accumbens (NAc) and prefrontal cortex (PFC). Our findings indicate that high-frequency (130 Hz) DBS at different amperages, 150 µA and 200 µA in the ACC during the acquisition phase of morphine conditioned place preference (CPP) inhibited the rewarding properties of morphine. Furthermore, DBS at these intensities during the extinction phase facilitated the extinction and mitigated the reinstatement of morphine CPP triggered by drug priming. Morphine conditioning was associated with impaired novel object conditioning (NOR) and locomotor activity. While DBS in the acquisition and extinction phases at both intensities restored NOR memory, only DBS at 200 µA recovered locomotor activity in the open field test. Treatment with DBS at 200 µA decreased c-Fos protein expression in the NAc and PFC (compared to morphine-only group). In conclusion, our data indicate an intensity-dependent effect of ACC DBS on the acquisition, extinction, and reinstatement of morphine-induced CPP in rats. These findings suggest that ACC DBS could be a potential intervention for the treatment of morphine use disorder.https://doi.org/10.1038/s41598-025-86279-2AddictionDeep brain stimulationMorphineAnterior cingulate cortex |
| spellingShingle | Mahdi Fatemizadeh Esmail Riahi Gholamreza Hassanzadeh Anahita Torkaman-Boutorabi Forough Radfar Maryam Farahmandfar Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies Scientific Reports Addiction Deep brain stimulation Morphine Anterior cingulate cortex |
| title | Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies |
| title_full | Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies |
| title_fullStr | Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies |
| title_full_unstemmed | Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies |
| title_short | Deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies |
| title_sort | deep brain stimulation of the anterior cingulate cortex reduces opioid addiction in preclinical studies |
| topic | Addiction Deep brain stimulation Morphine Anterior cingulate cortex |
| url | https://doi.org/10.1038/s41598-025-86279-2 |
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