Acute stress eliminated a key form of synaptic plasticity in the insular cortex-to-nucleus accumbens pathway in male rats but not females, and this effect was reversed by blocking CB1 receptors.
Neuroscientists studying stress, sex differences, or the endocannabinoid system.
What the researchers found
Under basal conditions, males showed equal proportions of LTP and LTD in the insular cortex-to-NAc pathway, while females predominantly showed LTP. Stress eliminated LTD in males 24 hours after exposure, reversed by CB1 receptor blockade. Females showed no stress-induced plasticity changes.
Why it matters
The insular cortex processes interoceptive signals and sends them to the reward center. Stress-induced disruption of this pathway could explain why stress alters reward processing in males, while females may be protected through different baseline circuit properties.
The numbers in context
Males: 50/50 LTP/LTD at baseline, LTD eliminated 24h post-stress. Females: predominantly LTP at baseline, no change with stress. CB1 blockade reversed the male-specific effect.
How the study worked
Male and female rats underwent 2 hours of acute restraint stress. In vivo electrophysiological recordings of the anterior insular cortex-to-NAc core pathway were performed immediately and 24 hours post-stress. CB1 receptor blockade tested systemically and locally.
What this study cannot tell us
Acute restraint stress is one paradigm and may not generalize. Only one circuit was examined. Functional consequences were not directly tested.
How to read the evidence
Rigorous electrophysiology with both systemic and local pharmacological validation, though limited to one stress paradigm and one neural circuit.
When this study was published
2025 publication.
The bigger picture
Sex differences in stress vulnerability are well documented clinically but poorly understood mechanistically. This study identifies a specific circuit and molecular mechanism that differs fundamentally between sexes.
Questions still open
- Does the baseline sex difference in insular-NAc plasticity explain differential vulnerability to stress-related psychiatric disorders?
- Would chronic stress produce similar or different plasticity changes?
Common questions
What is the insular cortex-nucleus accumbens pathway?
Why are females protected from this stress effect?
Read the original research
Sex-dependent effects of stress on aIC-NAc circuit neuroplasticity: Role of the endocannabinoid system.
Progress in neuro-psychopharmacology & biological psychiatry, 138, 111335
Citation
Gauthier, Manon; Hebert, Léo-Paul; Dugast, Emilie; Lardeux, Virginie; Letort, Kevin; Thiriet, Nathalie; Belnoue, Laure; Balado, Eric; Solinas, Marcello; Belujon, Pauline. (2025). Sex-dependent effects of stress on aIC-NAc circuit neuroplasticity: Role of the endocannabinoid system.. Progress in neuro-psychopharmacology & biological psychiatry, 138, 111335. https://doi.org/10.1016/j.pnpbp.2025.111335
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