The Kappa Opioid Receptor and the Sleep of Reason: Cortico-Subcortical Imbalance Following Salvinorin-A.
Por:
Ona G, Sampedro F, Romero-Lafuente S, Valle M, Camacho V, Migliorelli C, Mañanas MA, Antonijoan RM, Puntes M, Coimbra J, Ballester MR, Garrido M and Riba J
Publicada:
12 ene 2022
Resumen:
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Filiaciones:
Ona G:
Human Neuropsychopharmacology Group, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
Sampedro F:
Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación en Red-Enfermedades Neurodegenerativas (CIBERNED), Barcelona, Spain
Romero-Lafuente S:
Department of Automatic Control (ESAII), Biomedical Engineering Research Center (CREB), Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain
Valle M:
Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain
Camacho V:
Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Migliorelli C:
Department of Automatic Control (ESAII), Biomedical Engineering Research Center (CREB), Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain
Mañanas MA:
Department of Automatic Control (ESAII), Biomedical Engineering Research Center (CREB), Universitat Politècnica de Catalunya (UPC), Barcelona, Spain
Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Barcelona, Spain
Antonijoan RM:
Departament de Farmacologia i Terapèutica, Universitat Autònoma de Barcelona, Barcelona, Spain
Centre d'Investigació de Medicaments, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
Servei de Farmacologia Clínica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain
Puntes M:
Centre d'Investigació de Medicaments, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
Coimbra J:
Centre d'Investigació de Medicaments, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
Ballester MR:
Centre d'Investigació de Medicaments, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Spain
Blanquerna School of Health Science, Universitat Ramon Llull, Barcelona, Spain
Garrido M:
Centre d'Investigació de Medicaments, Sant Pau Institute of Biomedical Research (IIB-Sant Pau), Barcelona, Spain
Riba J:
Department of Neuropsychology and Psychopharmacology, Maastricht University, 6229 Maastricht, The Netherlands
Open Access
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