A Common Gut Bacterium Enhances Amphetamine Dependency Through Dopamine Elevation
Amphetamines, recognized for boosting dopamine, the essential reward molecule in the brain, are utilized to treat neuropsychiatric conditions like ADHD but are also frequently misused. Presently, no sanctioned therapies exist for amphetamine dependence, which is swiftly escalating globally. A research team at the University of Alabama at Birmingham, spearheaded by Angela Carter and Aurelio Galli, has discovered that opportunistic gut bacteria, including Fusobacterium nucleatum, can amplify the effects of amphetamines by modulating dopamine signaling within the brain.
Earlier studies indicated that administering antibiotics to mice diminished their reaction to amphetamines, yet the underlying mechanism was unknown. Galli observes, “We began to contemplate what these bacteria were excreting and how this might impact brain activities.” Research demonstrates that individuals reliant on amphetamines frequently have elevated levels of F. nucleatum in their intestines, a bacterium usually linked with periodontal disease, suggesting a microbial role in addiction.
In trials involving fruit flies, scientists discovered that the introduction of F. nucleatum heightened hyperactive behaviors and intensified responses to amphetamines. The bacterium’s influence was associated with the release of butyrate, a short-chain fatty acid recognized for its ability to traverse the blood-brain barrier, impacting neuronal functions by inhibiting histone deacetylases (HDACs). This inhibition facilitates the activation of specific genes, including those responsible for generating dopamine transporter proteins, which increase dopamine outflow when stimulated by amphetamines.
Real-time measurements of neurotransmitters verified that exposure to both butyrate and F. nucleatum resulted in heightened dopamine release. Disabling HDAC1 in neurons replicated the effects of the bacterium, corroborating the mechanism. The specificity of this pathway was further validated when other gut microbes or fatty acids failed to yield similar outcomes. The results were also corroborated in nematode worms.
Erin Calipari from Vanderbilt University remarks that this investigation offers a mechanistic insight into how gut bacteria modulate dopamine pathways. The results indicate possible therapeutic strategies, such as employing antibiotics to diminish the presence of F. nucleatum or formulating treatments aimed specifically at the bacterium.
Grasping these mechanisms paves the way for more sophisticated therapeutic designs, potentially facilitating the creation of effective treatments for amphetamine addiction.