The Kappa Opioid Receptor and the Sleep of Reason: Cortico-Subcortical Imbalance Following Salvinorin-A
Por:
Ona, G, Sampedro, F, Romero, S, Valle, M, Camacho, V, Migliorelli, C, Mananas, MA, Antonijoan, RM, Puntes, M, Coimbra, J, Ballester, MR, Garrido, M, Riba, J
Publicada:
1 ene 2022
Ahead of Print:
1 sep 2021
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:
St Pau Inst Biomed Res IIB St Pau, Human Neuropsychopharmacol Grp, Barcelona, Spain
Sampedro, F:
St Pau Inst Biomed Res IIb St Pau, Barcelona, Spain
Ctr Invest Red Enfermedades Neurodegenerat CIBERN, Barcelona, Spain
Romero, S:
Univ Politecn Catalunya UPC, Biomed Engn Res Ctr CREB, Dept Automat Control ESAII, Barcelona, Spain
Biomed Res Networking Ctr Bioengn Biomat & Nanome, Barcelona, Spain
Valle, M:
Univ Autonoma Barcelona, Dept Farmacol & Terapeut, Barcelona, Spain
Camacho, V:
Hosp Santa Creu & Sant Pau, Nucl Med Dept, Barcelona, Spain
Migliorelli, C:
Univ Politecn Catalunya UPC, Biomed Engn Res Ctr CREB, Dept Automat Control ESAII, Barcelona, Spain
Biomed Res Networking Ctr Bioengn Biomat & Nanome, Barcelona, Spain
Mananas, MA:
Univ Politecn Catalunya UPC, Biomed Engn Res Ctr CREB, Dept Automat Control ESAII, Barcelona, Spain
Biomed Res Networking Ctr Bioengn Biomat & Nanome, Barcelona, Spain
Antonijoan, RM:
Univ Autonoma Barcelona, Dept Farmacol & Terapeut, Barcelona, Spain
St Pau Inst Biomed Res IIB St Pau, Ctr Invest Medicaments, Barcelona, Spain
Hosp Santa Creu & Sant Pau, Serv Farmacol Clin, Barcelona, Spain
CIBERSAM, Ctr Invest Biomed Red Salud Mental, Barcelona, Spain
Puntes, M:
St Pau Inst Biomed Res IIB St Pau, Ctr Invest Medicaments, Barcelona, Spain
Coimbra, J:
St Pau Inst Biomed Res IIB St Pau, Ctr Invest Medicaments, Barcelona, Spain
Ballester, MR:
St Pau Inst Biomed Res IIB St Pau, Ctr Invest Medicaments, Barcelona, Spain
CIBERSAM, Ctr Invest Biomed Red Salud Mental, Barcelona, Spain
Univ Ramon Llull, Blanquerna Sch Hlth Sci, Barcelona, Spain
Garrido, M:
St Pau Inst Biomed Res IIB St Pau, Ctr Invest Medicaments, Barcelona, Spain
Riba, J:
Maastricht Univ, Dept Neuropsychol & Psychopharmacol, Maastricht, Netherlands
Green Published, gold, All Open Access, Gold, Green
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