ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Stress produces aversion and potentiates cocaine reward by releasing endogenous dynorphins in the ventral striatum to locally stimulate serotonin reuptake.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 122 citations in OpenAlex.
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- Dorsal raphe nucleus enkephalin peptide modulates behavioral preference.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
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- Kappa Opioid Receptors Control a Stress-Sensitive Brain Circuit and Drive Cocaine Seeking.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Highly sensitive in vivo detection of dynamic changes in enkephalins following acute stress in mice.eLife · 2025Article
- Shifted Balance Between Ventral Striatal Prodynorphin and Proenkephalin Biases Development of Cocaine Place Avoidance.Addiction biology · 2025Article
- Threonine-53 Phosphorylation of Dopamine Transporter Dictates κ-Opioid Receptor-Mediated Locomotor Suppression, Aversion, and Cocaine Reward.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
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- Molecular Modeling and In Vitro Functional Analysis of the RGS12 PDZ Domain Variant Associated with High-Penetrance Familial Bipolar Disorder.International journal of molecular sciences · 2024Article
- Dysregulation of kappa opioid receptor neuromodulation of lateral habenula synaptic function following a repetitive mild traumatic brain injury.Pharmacology, biochemistry, and behavior · 2024Article
- Co-targeting the kappa opioid receptor and dopamine transporter reduces motivation to self-administer cocaine and partially reverses dopamine system dysregulation.Scientific reports · 2024Article
- Endogenous opioid system modulates conditioned cocaine reward in a sex-dependent manner.Addiction biology · 2023Article
- Kappa Opioid Receptors Reduce Serotonin Uptake and Escitalopram Efficacy in the Mouse Substantia Nigra Pars Reticulata.International journal of molecular sciences · 2023Article
- Modulation of 5-HT release by dynorphin mediates social deficits during opioid withdrawal.Neuron · 2022Article
- Corticotropin releasing factor and drug seeking in substance use disorders: Preclinical evidence and translational limitations.Addiction neuroscience · 2022Article
- Stress decreases serotonin tone in the nucleus accumbens in male mice to promote aversion and potentiate cocaine preference via decreased stimulation of 5-HTNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- An updated assessment of the translational promise of G-protein-biased kappa opioid receptor agonists to treat pain and other indications without debilitating adverse effects.Pharmacological research · 2022Review
- Amygdala dynorphin/κ opioid receptor system modulates depressive-like behavior in mice following chronic social defeat stress.Acta pharmacologica Sinica · 2022Article
- Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Activation of the dynorphin/κ-opioid receptor (KOR) system by repeated stress exposure or agonist treatment produces place aversion, social avoidance, and reinstatement of extinguished cocaine place preference behaviors by stimulation of p38α MAPK, which subsequently causes the translocation of the serotonin transporter (SERT, SLC6A4) to the synaptic terminals of serotonergic neurons. In the present study we extend those findings by showing that stress-induced potentiation of cocaine conditioned place preference occurred by a similar mechanism. In addition, SERT knock-out mice did not show KOR-mediated aversion, and selective reexpression of SERT by lentiviral injection into the dorsal raphe restored the prodepressive effects of KOR activation. Kinetic analysis of several neurotransporters demonstrated that repeated swim stress exposure selectively increased the V(max) but not K(m) of SERT without affecting dopamine transport or the high-capacity, low-affinity transporters. Although the serotonergic neurons in the dorsal raphe project throughout the forebrain, a significant stress-induced increase in cell-surface SERT expression was only evident in the ventral striatum, and not in the dorsal striatum, hippocampus, prefrontal cortex, amygdala, or dorsal raphe. Stereotaxic microinjections of the long-lasting KOR antagonist norbinaltorphimine demonstrated that local KOR activation in the nucleus accumbens, but not dorsal raphe, mediated this stress-induced increase in ventral striatal surface SERT expression. Together, these results support the hypothesis that stress-induced activation of the dynorphin/KOR system produces a transient increase in serotonin transport locally in the ventral striatum that may underlie some of the adverse consequences of stress exposure, including the potentiation of the rewarding effects of cocaine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.