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Serotonin modulates nucleus accumbens circuits to suppress aggression
Zihui Zhang1, Gavin C Touponse1, Pia J Alderman1
1Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Biorxiv : the Preprint Server for Biology
|December 15, 2025
Summary
Serotonin (5-hydroxytryptamine; 5HT) levels increase during aggression, inhibiting specific neurons in the nucleus accumbens to suppress attacks. This reveals a new serotonin-mediated pathway for controlling aggressive behavior.
Area of Science:
- Neuroscience
- Behavioral Science
- Neuropharmacology
Background:
- Serotonin (5-hydroxytryptamine; 5HT) is traditionally viewed as anti-aggressive.
- The precise neural circuits and mechanisms through which 5HT modulates aggression are not fully understood.
Purpose of the Study:
- To investigate the role of serotonin in regulating aggressive behavior.
- To identify the specific neural pathways and neuronal populations involved in 5HT-mediated aggression control.
Main Methods:
- Utilized fiber photometry and optogenetics in double-transgenic mice.
- Employed miniaturized microscope recordings to monitor neural activity.
- Measured 5HT levels in the nucleus accumbens during aggressive encounters.
Main Results:
- Observed a significant increase in 5HT levels within the nucleus accumbens during aggressive episodes.
- Found that elevated 5HT inhibits a specific subset of D1 medium spiny neurons.
- Demonstrated that this inhibition leads to the suppression of aggressive attacks.
Conclusions:
- Identified a novel neuromodulatory mechanism where serotonin actively limits aggressive behavior.
- Revealed that the nucleus accumbens and D1 medium spiny neurons are critical components of this 5HT-regulated circuit.
- Provides new insights into the neurobiological underpinnings of aggression.
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