A noradrenergic–dopaminergic mechanism in the dorsal raphe nucleus contributing to reduced reward sensitivity under stress
Raffaella Tonini
Senior Reseacher Tenured – Director Neuromodulation of Cortical and Subcortical Circuits (NmCS)
IIT – Genova

Résumé
Stressful or traumatic life events are major risk factors for psychiatric disorders, including Major Depressive Disorder (MDD). Among its core symptoms, anhedonia, the reduced capacity to experience pleasure, is both highly prevalent and notably resistant to treatment. Anhedonia has been associated with dysregulation of monoaminergic signaling, yet the underlying circuit mechanisms remain poorly defined.
The dorsal raphe nucleus (DRN) is a highly heterogeneous monoaminergic hub involved in valence processing, comprising not only serotonergic neurons but also a population of dopaminergic neurons (DRNADA) that respond to both rewarding and aversive stimuli. While DRNADA neurons are known to integrate reward-related inputs, the sources and mechanisms conveying stress- or aversion-related signals to this circuit are less well understood. Anatomical evidence indicates that the DRN receives dense noradrenergic input from the locus coeruleus (LC), a key regulator of arousal and stress responses.
Using a combination of optogenetics, chemogenetics, and fiber photometry, we investigated how LC-derived noradrenergic signaling modulates DRN dopaminergic circuits under stress-related conditions. In particular, we examined the role of noradrenaline-dependent endocannabinoid signaling within the DRN and its potential influence on the integration of reward-related inputs to DRNADA neurons. This work provides a circuit-level framework for understanding how stress-responsive neuromodulatory systems may interact with reward-processing pathways in the context of anhedonia.

Invitée par David Robbe
Mardi 10 février 2026 à 11h – Salle de conférence de l’Inmed