The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models
Cocaine use disorder remains a major global health concern, with growing evidence that the gut microbiome modulates drug-related behaviors. This study examines the microbiome’s role in cocaine-induced psychomotor activation and context-dependent reward responses using germ-free (GF) and antibiotic-t...
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2025-01-01
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| author | Andrew D. Winters Dina M. Francescutti David J. Kracht Diptaraj S. Chaudhari Branislava Zagorac Mariana Angoa-Perez |
| author_facet | Andrew D. Winters Dina M. Francescutti David J. Kracht Diptaraj S. Chaudhari Branislava Zagorac Mariana Angoa-Perez |
| author_sort | Andrew D. Winters |
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| description | Cocaine use disorder remains a major global health concern, with growing evidence that the gut microbiome modulates drug-related behaviors. This study examines the microbiome’s role in cocaine-induced psychomotor activation and context-dependent reward responses using germ-free (GF) and antibiotic-treated (ABX) models. In GF mice, the absence of a microbiome blunted cocaine-induced psychomotor activation (<i>p</i> = 0.013), which was restored after conventionalization. GF mice also showed reduced cocaine-conditioned place preference (CPP) (<i>p</i> = 0.002), which normalized after conventionalization. Dopaminergic function, critical for psychomotor responses and reward, was microbiome-dependent, with increased dopamine levels (<i>p</i> = 0.009) and normalized turnover ratios after conventionalization. In the ABX model, microbiome depletion reduced both cocaine-induced locomotion and CPP responses (<i>p</i> ≤ 0.009), further supporting the role of gut microbes in modulating psychomotor and reward behaviors. ABX-treated mice also showed significant declines in microbial diversity, shifts in bacterial structure, and dysregulation in metabolic, immune, and neurotransmitter pathways (<i>p</i> ≤ 0.0001), including alterations in short-chain fatty acids and gamma-aminobutyric acid metabolism. These findings highlight the gut microbiome’s critical role in regulating cocaine’s psychomotor and rewarding effects, offering insights into potential therapeutic strategies for cocaine use disorder. |
| format | Article |
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| institution | Kabale University |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Microorganisms |
| spelling | doaj-art-b4017bd58f3244898cf0356e5bb28a0a2025-01-24T13:42:33ZengMDPI AGMicroorganisms2076-26072025-01-011317710.3390/microorganisms13010077The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal ModelsAndrew D. Winters0Dina M. Francescutti1David J. Kracht2Diptaraj S. Chaudhari3Branislava Zagorac4Mariana Angoa-Perez5Department of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USADepartment of Physiology, School of Medicine, Wayne State University, Detroit, MI 48201, USACocaine use disorder remains a major global health concern, with growing evidence that the gut microbiome modulates drug-related behaviors. This study examines the microbiome’s role in cocaine-induced psychomotor activation and context-dependent reward responses using germ-free (GF) and antibiotic-treated (ABX) models. In GF mice, the absence of a microbiome blunted cocaine-induced psychomotor activation (<i>p</i> = 0.013), which was restored after conventionalization. GF mice also showed reduced cocaine-conditioned place preference (CPP) (<i>p</i> = 0.002), which normalized after conventionalization. Dopaminergic function, critical for psychomotor responses and reward, was microbiome-dependent, with increased dopamine levels (<i>p</i> = 0.009) and normalized turnover ratios after conventionalization. In the ABX model, microbiome depletion reduced both cocaine-induced locomotion and CPP responses (<i>p</i> ≤ 0.009), further supporting the role of gut microbes in modulating psychomotor and reward behaviors. ABX-treated mice also showed significant declines in microbial diversity, shifts in bacterial structure, and dysregulation in metabolic, immune, and neurotransmitter pathways (<i>p</i> ≤ 0.0001), including alterations in short-chain fatty acids and gamma-aminobutyric acid metabolism. These findings highlight the gut microbiome’s critical role in regulating cocaine’s psychomotor and rewarding effects, offering insights into potential therapeutic strategies for cocaine use disorder.https://www.mdpi.com/2076-2607/13/1/77germ-freeantibioticsgut microbiotacocaine |
| spellingShingle | Andrew D. Winters Dina M. Francescutti David J. Kracht Diptaraj S. Chaudhari Branislava Zagorac Mariana Angoa-Perez The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models Microorganisms germ-free antibiotics gut microbiota cocaine |
| title | The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models |
| title_full | The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models |
| title_fullStr | The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models |
| title_full_unstemmed | The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models |
| title_short | The Gut Microbiome Regulates the Psychomotor Effects and Context-Dependent Rewarding Responses to Cocaine in Germ-Free and Antibiotic-Treated Animal Models |
| title_sort | gut microbiome regulates the psychomotor effects and context dependent rewarding responses to cocaine in germ free and antibiotic treated animal models |
| topic | germ-free antibiotics gut microbiota cocaine |
| url | https://www.mdpi.com/2076-2607/13/1/77 |
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