Differential Effect of Orexin-1 and CRF-1 Antagonism on Stress Circuits: a fMRI Study in the Rat with the Pharmacological Stressor Yohimbine
العنوان: | Differential Effect of Orexin-1 and CRF-1 Antagonism on Stress Circuits: a fMRI Study in the Rat with the Pharmacological Stressor Yohimbine |
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المؤلفون: | Angelo Bifone, Stefano Lepore, Emilio Merlo-Pich, Elena Vicentini, Alessandro Gozzi |
المصدر: | Neuropsychopharmacology. 38:2120-2130 |
بيانات النشر: | Springer Science and Business Media LLC, 2013. |
سنة النشر: | 2013 |
مصطلحات موضوعية: | Male, Agonist, medicine.drug_class, Aminopyridines, Gyrus Cinguli, Receptors, Corticotropin-Releasing Hormone, Dopamine receptor D1, Neurochemical, Piperidines, Extended amygdala, Dopamine, Neural Pathways, Adrenergic alpha-2 Receptor Agonists, medicine, Animals, Pyrroles, Pharmacology, Functional Neuroimaging, Yohimbine, Adrenergic alpha-2 Receptor Antagonists, Benzazepines, Medetomidine, Amygdala, Corpus Striatum, Orexin receptor, Rats, Orexin, Psychiatry and Mental health, Pyrimidines, Dopamine Antagonists, Orexin Receptor Antagonists, Original Article, Corticosterone, Psychology, Neuroscience, Stress, Psychological, medicine.drug |
الوصف: | 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. |
تدمد: | 1740-634X 0893-133X |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5cf1b3e1087b96b129fd753424a94411 https://doi.org/10.1038/npp.2013.109 |
حقوق: | OPEN |
رقم الأكسشن: | edsair.doi.dedup.....5cf1b3e1087b96b129fd753424a94411 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 1740634X 0893133X |
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