ArticleThe Journal of physiology2008
Corticotropin-releasing factor increases mouse ventral tegmental area dopamine neuron firing through a protein kinase C-dependent enhancement of Ih.
Article in The Journal of physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 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
168 citing papers in PubMed, 261 citations in OpenAlex.
- From Stress to Substance Use Disorders: The Expanding Role of Microglia-Astrocyte Crosstalk in Neuroimmune and Glutamate Alterations in the Nucleus Accumbens.International journal of molecular sciences · 2025Review
- Reward-associated cues reduce H-current amplitude in midbrain dopamine neurons.Neuropharmacology · 2025Article
- Brain-Wide Patterns of CRF Receptor 1 Expression in the Transgenic CRFR1-Cre-2a-tdTom Rat.The Journal of comparative neurology · 2025Article
- Untangling the multifaceted VTA responses to stress.Trends in neurosciences · 2025Review
- Translating stress systems: corticotropin releasing factor, its receptors, and the dopamine system in nonhuman primate models.Genomic psychiatry : advancing science from genes to society · 2025Article
- Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025Review
- Reducing stress and alcohol-related behaviors by targeting D1-CRHR1 receptor interactions in the amygdala.Frontiers in pharmacology · 2025Article
- The Formation and Function of the VTA Dopamine System.International journal of molecular sciences · 2024Review
- Hypothalamic CRF neurons facilitate brain reward function.Current biology : CB · 2024Article
- Chronic Nicotine Consumption and Withdrawal Regulate Melanocortin Receptor, CRF, and CRF Receptor mRNA Levels in the Rat Brain.Brain sciences · 2024Article
- Corticotropin-releasing factor-dopamine interactions in male and female macaque: Beyond the classic VTA.Synapse (New York, N.Y.) · 2024Article
- Chemogenetic activation of corticotropin-releasing factor-expressing neurons in the anterior bed nucleus of the stria terminalis reduces effortful motivation behaviors.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Corticotropin-releasing factor and GABA in the ventral tegmental area modulate partner preference formation in male and female prairie voles (Frontiers in neuroscience · 2024Article
- The Impact of Heroin Self-Administration and Environmental Enrichment on Ventral Tegmental CRF1 Receptor Expression.The international journal of neuropsychopharmacology · 2023Article
- Deficiency of Cullin 3, a Protein Encoded by a Schizophrenia and Autism Risk Gene, Impairs Behaviors by Enhancing the Excitability of Ventral Tegmental Area (VTA) DA Neurons.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- HCN channel inhibitor induces ketamine-like rapid and sustained antidepressant effects in chronic social defeat stress model.Neurobiology of stress · 2023Article
- Sex-dependent effects of acute stress on amyloid-β in male and female mice.Brain : a journal of neurology · 2023Article
- Sleep Deprivation Induces Dopamine System Maladaptation and Escalated Corticotrophin-Releasing Factor Signaling in Adolescent Mice.Molecular neurobiology · 2023Article
- Preservation of dendritic D2 receptor transmission in substantia nigra dopamine neurons with age.Scientific reports · 2023Article
- Corticotropin releasing factor and drug seeking in substance use disorders: Preclinical evidence and translational limitations.Addiction neuroscience · 2022Article
108 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Stress induces the release of the peptide corticotropin-releasing factor (CRF) into the ventral tegmental area (VTA), and also increases dopamine levels in brain regions receiving dense VTA input. Therefore, stress may activate the mesolimbic dopamine system in part through the actions of CRF in the VTA. Here, we explored the mechanism by which CRF affects VTA dopamine neuron firing. Using patch-clamp recordings from brain slices we first determined that the presence of I(h) is an excellent predictor of dopamine content in mice. We next showed that CRF dose-dependently increased VTA dopamine neuron firing, which was prevented by antagonism of the CRF receptor-1 (CRF-R1), and was mimicked by CRF-R1 agonists. Inhibition of the phospholipase C (PLC)-protein kinase C (PKC) signalling pathway, but not the cAMP-protein kinase A (PKA) signalling pathway, prevented the increase in dopamine neuron firing by CRF. Furthermore, the effect of CRF on VTA dopamine neurons was not attenuated by blockade of I(A), I(K(Ca)) or I(Kir), but was completely eliminated by inhibition of I(h). Although cAMP-dependent modulation of I(h) through changes in the voltage dependence of activation is well established, we surprisingly found that CRF, through a PKC-dependent mechanism, enhanced I(h) independent of changes in the voltage dependence of activation. Thus, our results demonstrated that CRF acted on the CRF-R1 to stimulate the PLC-PKC signalling pathway, which in turn enhanced I(h) to increase VTA dopamine neuron firing. These findings provide a cellular mechanism of the interaction between CRF and dopamine, which can be involved in promoting the avoidance of threatening stimuli, the pursuit of appetitive behaviours, as well as various psychiatric conditions.
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.