The Kappa Opioid Receptor and the Sleep of Reason

The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly select...

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Detalles Bibliográficos
Autores: Oña, Genís|||0000-0003-2741-2876, Sampedro, Frederic|||0000-0002-3933-1355, Romero, Sergio, Valle, Marta|||0000-0002-3515-251X, Camacho, Valle|||0000-0003-0748-0847, Migliorelli, Carolina|||0000-0003-2781-8841, Mañanas, Miguel Ángel, Antonijoan Arbós, Rosa Ma (Rosa María)|||0000-0002-7099-5125, Puntes, Montserrat, Coimbra, Jimena, Ballester, Maria Rosa|||0000-0002-0472-9558, Garrido, Maite, Riba, Jordi|||0000-0002-9375-8421
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:284376
Acceso en línea:https://ddd.uab.cat/record/284376
https://dx.doi.org/urn:doi:10.1093/ijnp/pyab063
Access Level:acceso abierto
Palabra clave:EEG
Hallucinogens
Kappa opioid receptor
Opioids
Salvinorin-a
SPECT
Descripción
Sumario:The mechanisms through which kappa opioid receptor (KOR) agonists induce psychotomimetic effects are largely unknown, although the modulation of this receptor has attracted attention for its clinical use. In this work, we characterize the neuropharmacological effects of salvinorin-A, a highly selective KOR agonist. Changes in multimodal electroencephalography, single-photon emission computed tomography, and subjective effects following the acute administration of salvinorin-A are reported. The study included 2 sub-studies that employed a double-blind, crossover, randomized, placebo-controlled design. The electroencephalography measures showed a marked increase in delta and gamma waves and a decrease in alpha waves while subjects were under the effect of salvinorin-A. Regarding single-photon emission computed tomography measures, significant decreases in regional cerebral blood flow were detected in multiple regions of the frontal, temporal, parietal, and occipital cortices. Significant regional cerebral blood flow increases were observed in some regions of the medial temporal lobe, including the amygdala, the hippocampal gyrus, and the cerebellum. The pattern of subjective effects induced by salvinorin-A was similar to those observed in relation to other psychotomimetic drugs but with an evidently dissociative nature. No dysphoric effects were reported. The salvinorin-A-mediated KOR agonism induced dramatic psychotomimetic effects along with a generalized decrease in cerebral blood flow and electric activity within the cerebral cortex.