ArticleBiological psychiatry2014
Sex differences in sensitivity to the depressive-like effects of the kappa opioid receptor agonist U-50488 in rats.
Article in Biological psychiatry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
79 citing papers in PubMed, 108 citations in OpenAlex.
- κ-Opioid Receptor Plasma Levels Are Associated With Sex and Diagnosis of Major Depressive Disorder But Not Response to Ketamine.Journal of clinical psychopharmacologyTrial
- Stress-induced adaptations in nucleus accumbens dopamine D1 receptor-expressing cells correspond to social avoidance behavior in male mice.IBRO neuroscience reports · 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
- Astroglial kappa opioid receptor-mediated reduction of glutamate exchanger xCT in the prelimbic cortex underlies chronic stress-induced depressive-like behaviors.Molecular psychiatry · 2026Article
- Xylazine potentiates the interoceptive effects of fentanyl in male and female rats.Psychopharmacology · 2026Article
- Nalmefene and naltrexone reduce alcohol intake via selective efficacy in subpopulations distinguished by behavioral and blood-based biomarkers.Communications medicine · 2026Article
- Modulatory effects of orexin and dynorphin on stress-related alcohol seeking and relapse: pivotal role of the posterior paraventricular nucleus of the thalamus.Frontiers in pharmacology · 2026Review
- Nalfurafine is Aversive at Antinociceptive Doses in Mice.Pharmacology research & perspectives · 2025Article
- Depression of intracranial self-stimulation in male and female rats by intraperitoneal lactic acid: effects of morphine, ketoprofen, and interactions with G-protein biased kappa opioid agonists.Psychopharmacology · 2025Article
- Expression of Dynorphin and Kappa-Opioid Receptors in the Bed Nucleus of the Stria Terminalis: Focus on Adolescent Development.International journal of molecular sciences · 2025Article
- Kappa opioid receptors diminish spontaneous dopamine signals in awake mice through multiple mechanisms.Neuropharmacology · 2025Article
- The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.Psychopharmacology · 2025Article
- Endocannabinoid-mediated regulation of depression in the ovBNST.Frontiers in neuroscience · 2025Article
- The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction.Current addiction reports · 2025Review
- BLAbioRxiv : the preprint server for biology · 2024Article
- Sex chromosomes and hormones independently influence healthy brain development but act similarly after cranial radiation.Proceedings of the National Academy of Sciences of the United States of America · 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
- The ultrasonic vocalization (USV) syllable profile during neonatal opioid withdrawal and a kappa opioid receptor component to increased USV emissions in female mice.bioRxiv : the preprint server for biology · 2024Article
- Xylazine is an agonist at kappa opioid receptors and exhibits sex-specific responses to opioid antagonism.Addiction neuroscience · 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
19 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDynorphin, an endogenous ligand at kappa opioid receptors (KORs), produces depressive-like effects and contributes to addictive behavior in male nonhuman primates and rodents. Although comorbidity of depression and addiction is greater in women than men, the role of KORs in female motivated behavior is unknown.
methodsIn adult Sprague-Dawley rats, we used intracranial self-stimulation to measure effects of the KOR agonist (±)-trans-U-50488 methanesulfonate salt (U-50488) (.0-10.0 mg/kg) on brain stimulation reward in gonadally intact and castrated males and in females at estrous cycle stages associated with low and high estrogen levels. Pharmacokinetic studies of U-50488 in plasma and brain were conducted. Immunohistochemistry was used to identify sex-dependent expression of U-50488-induced c-Fos in brain.
resultsU-50488 dose-dependently increased the frequency of stimulation (threshold) required to maintain intracranial self-stimulation responding in male and female rats, a depressive-like effect. However, females were significantly less sensitive than males to the threshold-increasing effects of U-50488, independent of estrous cycle stage in females or gonadectomy in males. Although initial plasma concentrations of U-50488 were higher in females, there were no sex differences in brain concentrations. Sex differences in U-50488-induced c-Fos activation were observed in corticotropin releasing factor-containing neurons of the paraventricular nucleus of the hypothalamus and primarily in non-corticotropin releasing factor-containing neurons of the bed nucleus of the stria terminalis.
conclusionsThese data suggest that the role of KORs in motivated behavior of rats is sex-dependent, which has important ramifications for the study and treatment of mood-related disorders, including depression and drug addiction in people.
Indexed as
Identifiers
What OpenQuestion holds
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.