ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2013
Differential effect of orexin-1 and CRF-1 antagonism on stress circuits: a fMRI study in the rat with the pharmacological stressor Yohimbine.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 42 citations in OpenAlex.
- Yohimbine as a pharmacological probe for alcohol research: a systematic review of rodent and human studies.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Pooled it
- Neurochemical underpinning of hemodynamic response to neuropsychiatric drugs: A meta- and cluster analysis of preclinical studies.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Pooled it
- Functional Plasticity of Orexin/Hypocretin Neurons Balances Stress States.Biological psychiatry · 2026Review
- Pharmacological MRI: Utility in Understanding Drug Mechanisms in Psychiatric Disorders.Journal of magnetic resonance imaging : JMRI · 2026Review
- The anxiogenic drug yohimbine is a reinforcer in male and female rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Article
- Chemogenetic stimulation of tonic locus coeruleus activity strengthens the default mode network.Science advances · 2022Article
- The orexin (hypocretin) neuropeptide system is a target for novel therapeutics to treat cocaine use disorder with alcohol coabuse.Neuropharmacology · 2021Review
- Substituted Azabicyclo[2.2.1]heptanes as Selective Orexin-1 Antagonists: Discovery of JNJ-54717793.ACS medicinal chemistry letters · 2020Article
- Orexin and Alzheimer's Disease: A New Perspective.Psychiatry investigation · 2020Article
- Orexin/hypocretin receptor modulation of anxiolytic and antidepressive responses during social stress and decision-making: Potential for therapy.Brain research · 2020Review
- phMRI, neurochemical and behavioral responses to psychostimulants distinguishing genetically selected alcohol-preferring from genetically heterogenous rats.Addiction biology · 2019Article
- Corticotropin-Releasing Factor Receptor 1 in the Anterior Cingulate Cortex Mediates Maternal Absence-Induced Attenuation of Transport Response in Mouse Pups.Frontiers in cellular neuroscience · 2018Article
- Orexin 2 receptor regulation of the hypothalamic-pituitary-adrenal (HPA) response to acute and repeated stress.Neuroscience · 2017Article
- Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation.Frontiers in pharmacology · 2017Article
- Role of the Orexin/Hypocretin System in Stress-Related Psychiatric Disorders.Current topics in behavioral neurosciences · 2017Review
- Selective Inhibition of Orexin-2 Receptors Prevents Stress-Induced ACTH Release in Mice.Frontiers in behavioral neuroscience · 2017Article
- The highly selective orexin/hypocretin 1 receptor antagonist GSK1059865 potently reduces ethanol drinking in ethanol dependent mice.Brain research · 2016Article
- Article
- Orexin/hypocretin role in reward: implications for opioid and other addictions.British journal of pharmacology · 2015Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Translational approaches to study the neural substrates of stress and assess the mechanistic efficacy of novel anti-anxiety agents necessitate the use of stressors with a similar degree of saliency across species. The alpha-2 adrenoreceptor antagonist yohimbine represents an attractive experimental tool owing to its well-documented stress-inducing properties in humans and laboratory species. We investigated the neural substrates engaged by yohimbine in the rat brain by using functional magnetic resonance imaging and mapped their modulation by neurotransmitter systems involved in stress responses. Yohimbine elicited a composite pattern of brain activation, highlighting the recruitment of cortico-striato-thalamic regions and extra-hypothalamic stress neurocircuits. This effect was strongly attenuated by the α-2-adrenoceptor agonist medetomidine and by the dopamine (DA) D1 receptor antagonist SCH23390, thus revealing a primary contribution of both norepinephrine and DA on the neurofunctional cascade elicited by the drug. Pretreatment with the corticotrophin-releasing factor type-1 receptor (CRF1R) antagonist CP154,526 produced a region-dependent inhibition of yohimbine-induced activation in the amygdala, striatum, and cingulate cortex, while the orexin type-1 receptor (OX1R) antagonists GSK1059865 robustly inhibited the response in fronto-hippocampal regions as well as in several key components of the extended amygdala. CP154,526 and GSK1059865 did not prevent yohimbine-induced plasma corticosterone release, a finding that corroborates a central origin of the effects mapped. Our findings provide novel insight into the brain substrates and neurochemical mediators engaged by the stress-inducing agent yohimbine. The differential pattern of inhibition produced by CRF1R and OX1R antagonists suggests that these two neuropeptide systems can modulate the functional response to stress via distinct central neural pathways.
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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.