ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2016
Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 132 citations in OpenAlex.
- BLA kappa opioid receptor inputs to the BNST mediate social stress-induced increases in alcohol drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Adolescent social isolation promotes oxycodone consumption and augments mu opioid receptor responsiveness in the ventral pallidum.Addiction neuroscience · 2026Article
- Kappa opioid receptor antagonism in neuropsychiatry: from molecular mechanisms to clinical prospects.European archives of psychiatry and clinical neuroscience · 2026Review
- Examining the impact of adolescent social isolation on oxycodone sensitization.Psychopharmacology · 2026Article
- Triazole 187 is a biased KOR agonist that suppresses itch without sedation and induces anxiolytic-like behaviors in mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Effects of kappa-opioid receptor stimulation on addiction-related behavior in female rats: differences along the rostro-caudal axis of the nucleus accumbens shell.Psychopharmacology · 2026Article
- Effects of acute adolescent stress on the acquisition and maintenance of intravenous oxycodone self-administration in male and female rats.Drug and alcohol dependence · 2026Article
- Progressing from Simple to Multidimensional Models Towards a Biopsychosocial Framework of Addiction.Current addiction reports · 2026Review
- Adolescent social isolation associated changes in ethanol-induced dopamine regulation in the ventral pallidum.Addiction neuroscience · 2025Article
- Effects of acute adolescent stress on the acquisition and maintenance of intravenous oxycodone self-administration in male and female rats.bioRxiv : the preprint server for biology · 2025Article
- Kappa opioid receptors diminish spontaneous dopamine signals in awake mice through multiple mechanisms.Neuropharmacology · 2025Article
- Morphine-Induced Antinociception Is Potentiated and Dopamine Elevations Are Inhibited by the Biased Kappa Opioid Receptor Agonist Triazole 1.1.ACS chemical neuroscience · 2025Article
- A review of the effects of different types of social behaviors on the recruitment of neuropeptides and neurotransmitters in the nucleus accumbens.Frontiers in neuroendocrinology · 2025Review
- Long-term effects of adolescent versus adult nicotine self-administration on cholinergic modulation of dopamine in the nucleus accumbens core.Drug and alcohol dependence · 2025Article
- Adolescent Alcohol and the Spectrum of Cognitive Dysfunction in Aging.Advances in experimental medicine and biology · 2025Review
- BLAbioRxiv : the preprint server for biology · 2024Article
- Kappa-opioid receptor stimulation in the nucleus accumbens shell and ethanol drinking: Differential effects by rostro-caudal location and level of drinking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Environmental Deprivation Effects on Myelin Ultrastructure in Huntington Disease and Wildtype Mice.Molecular neurobiology · 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
- Adolescent social isolation increases binge-like alcohol drinking in male but not female high-alcohol-preferring mice.Alcohol and alcoholism (Oxford, Oxfordshire) · 2024Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Chronic early-life stress increases vulnerability to alcoholism and anxiety disorders during adulthood. Similarly, rats reared in social isolation (SI) during adolescence exhibit augmented ethanol intake and anxiety-like behaviors compared with group housed (GH) rats. Prior studies suggest that disruption of dopamine (DA) signaling contributes to SI-associated behaviors, although the mechanisms underlying these alterations are not fully understood. Kappa opioid receptors (KORs) have an important role in regulating mesolimbic DA signaling, and other kinds of stressors have been shown to augment KOR function. Therefore, we tested the hypothesis that SI-induced increases in KOR function contribute to the dysregulation of NAc DA and the escalation in ethanol intake associated with SI. Our ex vivo voltammetry experiments showed that the inhibitory effects of the kappa agonist U50,488 on DA release were significantly enhanced in the NAc core and shell of SI rats. Dynorphin levels in NAc tissue were observed to be lower in SI rats. Microdialysis in freely moving rats revealed that SI was also associated with reduced baseline DA levels, and pretreatment with the KOR antagonist nor-binaltorphimine (nor-BNI) increased DA levels selectively in SI subjects. Acute ethanol elevated DA in SI and GH rats and nor-BNI pretreatment augmented this effect in SI subjects, while having no effect on ethanol-stimulated DA release in GH rats. Together, these data suggest that KORs may have increased responsiveness following SI, which could lead to hypodopaminergia and contribute to an increased drive to consume ethanol. Indeed, SI rats exhibited greater ethanol intake and preference and KOR blockade selectively attenuated ethanol intake in SI rats. Collectively, the findings that nor-BNI reversed SI-mediated hypodopaminergic state and escalated ethanol intake suggest that KOR antagonists may represent a promising therapeutic strategy for the treatment of alcohol use disorders, particularly in cases linked to chronic early-life stress.
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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.