Stress disrupts brain reward circuit plasticity in male rats but not females, and the endocannabinoid system is responsible
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.
Quick Facts
What This Study 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.
Key Numbers
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 They Did This
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.
Why This Research 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 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.
What This Study Doesn't Tell Us
Acute restraint stress is one paradigm and may not generalize. Only one circuit was examined. Functional consequences were not directly tested.
Questions This Raises
- ?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?
Trust & Context
- Key Stat:
- Stress eliminated long-term depression in the insular-NAc pathway via the endocannabinoid system; females were unaffected
- Evidence Grade:
- Rigorous electrophysiology with both systemic and local pharmacological validation, though limited to one stress paradigm and one neural circuit.
- Study Age:
- 2025 publication.
- Original Title:
- Sex-dependent effects of stress on aIC-NAc circuit neuroplasticity: Role of the endocannabinoid system.
- Published In:
- Progress in neuro-psychopharmacology & biological psychiatry, 138, 111335 (2025)
- Authors:
- Gauthier, Manon, Hebert, Léo-Paul, Dugast, Emilie, Lardeux, Virginie, Letort, Kevin, Thiriet, Nathalie, Belnoue, Laure, Balado, Eric, Solinas, Marcello, Belujon, Pauline
- Database ID:
- RTHC-06517
Evidence Hierarchy
Tests effects in animals (usually mice or rats), not humans.
What do these levels mean? →Frequently Asked Questions
What is the insular cortex-nucleus accumbens pathway?
The insular cortex processes signals about internal body states and sends this information to the nucleus accumbens, a key reward and motivation center. This pathway helps translate internal states into motivated behavior.
Why are females protected from this stress effect?
Females showed predominantly LTP (not a balance of LTP and LTD) at baseline, meaning stress had no LTD to eliminate. This fundamentally different baseline circuit property may represent a sex-specific resilience mechanism.
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Cite This Study
https://rethinkthc.com/research/RTHC-06517APA
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
MLA
Gauthier, Manon, et al. "Sex-dependent effects of stress on aIC-NAc circuit neuroplasticity: Role of the endocannabinoid system.." Progress in neuro-psychopharmacology & biological psychiatry, 2025. https://doi.org/10.1016/j.pnpbp.2025.111335
RethinkTHC
RethinkTHC Research Database. "Sex-dependent effects of stress on aIC-NAc circuit neuroplas..." RTHC-06517. Retrieved from https://rethinkthc.com/research/gauthier-2025-sexdependent-effects-of-stress
Access the Original Study
Study data sourced from PubMed, a service of the U.S. National Library of Medicine, National Institutes of Health.
This study breakdown was produced by the RethinkTHC research team. We analyze and report published research findings without making health recommendations. All interpretations are based solely on the published abstract and study data.