Mapping serotonergic dynamics using drug-modulated molecular connectivity in rats.
Tudor M. Ionescu, Mario Amend, Rakibul Hafiz, Andreas Maurer, Bharat B. Biswal, Hans F. Wehrl, Kristina Herfert
Elife May 15, 2025 DOI: 10.7554/eLife.97864 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Intervention | Methylenedioxymethamphetamine (MDMA) |
| Dose | a single dose |
| Topics | Serotonin |
| Keywords | Functional MRI Functional connectivity Molecular connectivity Pharmacology Rat FMRI Brain Imaging PET Neuroimaging Brain scanning Brain mapping Neurotransmitter Neural circuits Serotonin 5-HT |
| Citations | 1 |
| Key findings | A single dose of MDMA produced clear changes in molecular connectivity, establishing a direct link between serotonin transporter occupancy and alterations in functional brain networks. |
Abstract
Understanding the complex workings of the brain is one of the most significant challenges in neuroscience, providing insights into normal brain function, neurological diseases, and the effects of potential therapeutics. A major challenge in this field lies in the limitations of traditional brain imaging techniques, which often capture only fragments of the complex puzzle of brain function. Our research employs a novel approach termed 'molecular connectivity' (MC), which combines the strengths of various imaging methods to provide a comprehensive view of how specific molecules, such as the serotonin transporter, interact across different brain regions and influence brain function. This innovative technique bridges the gap between functional magnetic resonance imaging (fMRI), known for its ability to monitor brain activity by tracking blood flow, and positron emission tomography (PET), which visualizes specific molecular changes. By integrating these methods, we can better understand how drugs influence brain function. Our study focuses on the application of dynamic [11C]DASB PET scans to map the distribution of serotonin transporters, key players in regulating mood and emotions, and examines how these transporters are altered following exposure to methylenedioxymethamphetamine (MDMA), which is commonly known as ecstasy. Through a detailed comparison of MC with traditional measures of brain connectivity, we reveal significant patterns that closely align with physiological changes. Our results revealed clear changes in molecular connectivity after a single dose of MDMA, establishing a direct link between the effects of drugs on serotonin transporter occupancy and changes in the functional brain network. This work offers a novel methodology for the in-depth study of brain function at the molecular level and opens new pathways for understanding how drugs modulate brain activity.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 4
- The effects of psilocybin and MDMA on between-network resting state functional connectivity in healthy volunteers Frontiers in Human Neuroscience May 27, 2014
- The Effects of Acutely Administered 3,4-Methylenedioxymethamphetamine on Spontaneous Brain Function in Healthy Volunteers Measured with Arterial Spin Labeling and Blood Oxygen Level–Dependent Resting State Functional Connectivity Biological Psychiatry January 10, 2014
- Receptor-Enriched Analysis of functional connectivity by targets (REACT): A novel, multimodal analytical approach informed by PET to study the pharmacodynamic response of the brain under MDMA Neuroimage April 4, 2019
- Neurovascular Uncoupling: Multimodal Imaging Delineates the Acute Effects of 3,4-Methylenedioxymethamphetamine Journal of Nuclear Medicine September 29, 2022