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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Microorganisms |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2607/13/1/77 |
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| Summary: | 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. |
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| ISSN: | 2076-2607 |