Longitudinal and Concurrent Changes in Brain and Gut due to Morphine Self-Administration

Area of Science:

• Neuroscience
• Microbiology
• Pharmacology

Background:

• Opioid agonists impact opioid and dopaminergic systems.
• Emerging research implicates the gut microbiome in opioid use disorders.
• The gut-brain axis (GBA) facilitates bidirectional communication between the brain and gut, but its spatiotemporal dynamics in opioid use are unclear.

Purpose of the Study:

• To investigate longitudinal and concurrent changes in the gut and brain during chronic morphine self-administration in rodents.
• To establish the temporal relationship between gut microbiome alterations and brain structural changes.

Main Methods:

• Rodents self-administered morphine (0.4 mg/kg/infusion) for 14 days.
• 16S rDNA fecal analysis assessed gut microbiota composition at baseline, acute (2 days), and chronic (14 days) phases.
• 7T MRI scans evaluated brain diffusivity indices at the same three time points.

Main Results:

• Significant changes in gut microbiota diversity and abundance were observed as early as the acute phase, persisting into the chronic phase.
• MRI revealed alterations in diffusivity indices, with significant effects in the striatum and thalamus.
• Gut microbiome alterations preceded the observed brain structural changes.

Conclusions:

• Morphine self-administration induces early and persistent changes in the gut microbiome.
• The striatum and thalamus are key brain regions affected by chronic opioid exposure.
• Gut microbiome shifts likely precede and influence brain alterations via the gut-brain axis in opioid use disorder.