Adolescent stress recruits a latent amygdala-dopamine circuit to drive punishment-resistant reward-seeking
Nadel, J. A.; Swanson, E. S.; Zhu, M.; Demir, B.; Kwon, M. H.; Patel, S.; Lerner, T. N.
Show abstract
Adolescent stress is a lifelong risk factor for addiction, but the underlying neural circuit changes remain unknown. Here, we show that chronic unpredictable stress in adolescent mice causes a prominent increase in punishment-resistant reward-seeking - behavior tightly linked to the diagnostic criteria for addiction - establishing a model for mechanistic investigation. Using this model, we find a "gain-of-function" in reward processing wherein persistent hyperexcitability in a subset of central amygdala (CeA) neurons projecting to the substantia nigra pars lateralis (SNL) disinhibits dopamine release in the tail of the striatum (TS), newly recruiting TS to participate in punishment-resistant reward-seeking. Normalizing circuit-specific CeA hyperexcitability or optogenetically counteracting excessive TS dopamine release prevented the increase in punishment resistance. These results identify a novel circuit mediator for the lifelong effects of adolescent stress on a core feature of addictive disorders, opening a new avenue for interventions targeted to at-risk populations with specific formative experiences.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A prefrontal cortex-lateral hypothalamus circuit controls stress-driven increased food intake 96%
- Distinct ventral tegmental area neuronal ensembles are indispensable for reward-driven approach and stress-driven avoidance behaviors 95%
- Synchronous activation of striatal cholinergic interneurons induces local serotonin release 94%
Similar papers in this journal
- Dual Engram Architecture within a Single Striatal Cell Type Distinctly Controls Alcohol Relapse and Extinction 96%
- Amygdala Reward Neurons Form and Store Fear Extinction Memory 95%
- Molecular and circuit determinants in the globus pallidus mediating control of cocaine-induced behavioral plasticity 94%
Similar papers in this journal
- Stress-activated neuronal ensemble in the supramammillary nucleus stores anxiety but not memory 95%
- The nucleus accumbens shell regulates hedonic feeding via a rostral hotspot 94%
- NPAS4 in the medial prefrontal cortex mediates chronic social defeat stress- induced anhedonia and dendritic spine loss 94%
Similar papers in this journal
- Identification of a stress-sensitive endogenous opioid-containing neuronal population in the paranigral ventral tegmental area. 95%
- Transcriptomic signatures of sex-specific nicotine sensitization and imprinting of self-administration in rats inform GWAS findings on human addiction phenotypes 95%
- Dorsomedial striatal neuroinflammation causes excessive goal-directed action control by disrupting astrocyte function 93%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.