Related Experiment Video
Updated: May 13, 2026
Intracerebroventricular Delivery of Gut-Derived Microbial Metabolites in Freely Moving Mice
Published on: June 2, 2022
Gut microbiota and SCFA dysregulation drive MDPV-induced behavioral and neuroimmune adaptations in male mice
Jincen Liu1, Yuying Bai2, Yue Feng1
1NHC Key Laboratory of Forensic Science, College of Forensic Medicine, Xi'an Jiaotong University, Xi'an, China; Bio-evidence Sciences Academy, Western China Science and Technology, Innovation Harbor, Xi'an Jiaotong University, Xi'an, China.
Background:
3,4-methylenedioxypyrovalerone (MDPV), a synthetic cathinone-derived novel psychoactive substance, exhibits potent stimulant effects and high abuse potential. However, the neurobiological mechanisms underlying MDPV dependence, particularly those involving the gut microbiota, remain unclear.
Methods:
Male C57BL/6 mice were used to establish an MDPV-induced behavioral sensitization model. Gut microbiota composition and short-chain fatty acids (SCFAs) were analyzed by 16S rRNA sequencing and metabolomics. Antibiotics and fecal microbiota transplantation (FMT) were employed to manipulate microbiota, while valeric acid supplementation was used to assess functional effects. Microglial activation and inflammatory cytokines in the VTA were evaluated.
Results:
Repeated MDPV administration (1 mg/kg) induced robust behavioral sensitization, accompanied by alterations in gut microbiota and SCFA profiles. Antibiotic-induced microbiota depletion abolished sensitization. FMT from control donors attenuated sensitization, whereas FMT from MDPV-treated donors restored it in antibiotic-treated mice. Valeric acid was significantly associated with behavioral outcomes, and its supplementation mitigated sensitization, reduced microglial activation in the VTA, and decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α).
Conclusions:
Gut microbiota and their metabolites, particularly valeric acid, regulate MDPV-induced behavioral sensitization by modulating neuroinflammation and microglial activation. Targeting microbiota-SCFA signaling may offer a potential therapeutic strategy for MDPV -induced neurobehavioral effects.
Insights
Gut microbiota influence 3,4-methylenedioxypyrovalerone (MDPV) dependence. Valeric acid, a gut metabolite, reduces MDPV-induced sensitization and neuroinflammation, suggesting a therapeutic target.
Area of Science:
- Neuroscience
- Microbiology
- Pharmacology
Background:
- 3,4-methylenedioxypyrovalerone (MDPV) is a potent synthetic cathinone with high abuse potential.
- The neurobiological basis of MDPV dependence, especially the role of gut microbiota, is not well understood.
Purpose of the Study:
- To investigate the impact of gut microbiota on MDPV-induced behavioral sensitization.
- To explore the role of short-chain fatty acids (SCFAs) and neuroinflammation in MDPV dependence.
Main Methods:
- Established an MDPV-induced behavioral sensitization model in mice.
- Analyzed gut microbiota and SCFA profiles using 16S rRNA sequencing and metabolomics.
- Utilized antibiotics, fecal microbiota transplantation (FMT), and valeric acid supplementation to assess microbiota function.
Main Results:
- MDPV induced behavioral sensitization, altered gut microbiota, and SCFA profiles.
- Microbiota depletion abolished sensitization; FMT modulated sensitization.
- Valeric acid supplementation mitigated sensitization, reduced VTA microglial activation, and decreased inflammatory cytokines.
Conclusions:
- Gut microbiota and valeric acid regulate MDPV-induced behavioral sensitization via neuroinflammation.
- Targeting microbiota-SCFA signaling presents a potential therapeutic strategy for MDPV-related neurobehavioral effects.
