Cortico-Amygdala-Striatal Activation by Modafinil/Flecainide Combination

Autor: Jian-Sheng Lin, Christian Giaume, Dominique Vodovar, Claire Leroy, Mathieu Charvériat, Nicolas Tournier, Yves Dauvilliers, Franck Mouthon, Géraldine Pottier, Adeline Duchêne, Catriona Wimberley
Přispěvatelé: Imagerie Moléculaire in Vivo (IMIV - U1023 - ERL9218), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Theranexus [Lyon], CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Integrated Physiology of the Brain Arousal Systems (WAKING), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Département de neurologie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), VODOVAR, Dominique, Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Centre de recherche en neurosciences de Lyon (CRNL), Université de Lyon-Université de Lyon-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
MESH: Flecainide
Cataplexy
[SDV]Life Sciences [q-bio]
narcolepsy
Modafinil
MESH: Rats
Sprague-Dawley
Striatum
Pharmacology
Regular Research Articles
MESH: Corpus Striatum
Rats
Sprague-Dawley
MESH: Modafinil
0302 clinical medicine
MESH: Fluorodeoxyglucose F18
MESH: Amygdala
MESH: Animals
Pharmacology (medical)
Cerebral Cortex
Voltage-Gated Sodium Channel Blockers
Flecainide
medicine.diagnostic_test
Wakefulness-Promoting Agents
Amygdala
MESH: Positron-Emission Tomography
3. Good health
[SDV] Life Sciences [q-bio]
[SDV.TOX] Life Sciences [q-bio]/Toxicology
Drug Combinations
Psychiatry and Mental health
medicine.anatomical_structure
Positron emission tomography
[SDV.TOX]Life Sciences [q-bio]/Toxicology
[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]
medicine.symptom
medicine.drug
FDG PET imaging
MESH: Rats
03 medical and health sciences
Fluorodeoxyglucose F18
medicine
Brain positron emission tomography
Animals
MESH: Drug Combinations
business.industry
MESH: Wakefulness-Promoting Agents
medicine.disease
MESH: Voltage-Gated Sodium Channel Blockers
Corpus Striatum
MESH: Male
MESH: Cerebral Cortex
neuroglia
Rats
030104 developmental biology
Positron-Emission Tomography
[SDV.MHEP.PSM]Life Sciences [q-bio]/Human health and pathology/Psychiatrics and mental health
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
astroglial connexin
business
030217 neurology & neurosurgery
Narcolepsy
Zdroj: International Journal of Neuropsychopharmacology
International Journal of Neuropsychopharmacology, 2018, 21 (7), pp.687-696. ⟨10.1093/ijnp/pyy027⟩
International Journal of Neuropsychopharmacology, Oxford University Press (OUP), 2018, 21 (7), pp.687-696. ⟨10.1093/ijnp/pyy027⟩
ISSN: 1469-5111
1461-1457
DOI: 10.1093/ijnp/pyy027
Popis: International audience; Background: Modafinil, a nonamphetaminic wake-promoting compound, is prescribed as first line therapy in narcolepsy, an invalidating disorder characterized by excessive daytime sleepiness and cataplexy. Although its mode of action remains incompletely known, recent studies indicated that modafinil modulates astroglial connexin-based gap junctional communication as administration of a low dose of flecainide, an astroglial connexin inhibitor, enhanced the wake-promoting and procognitive activity of modafinil in rodents and healthy volunteers. The aim of this study is to investigate changes in glucose cerebral metabolism in rodents, induced by the combination of modafinil+flecainide low dose (called THN102).Methods: The impact of THN102 on brain glucose metabolism was noninvasively investigated using 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography imaging in Sprague-Dawley male rats. Animals were injected with vehicle, flecainide, modafinil, or THN102 and further injected with 18F-2-fluoro-2-deoxy-D-glucose followed by 60-minute Positron Emission Tomography acquisition. 18F-2-fluoro-2-deoxy-D-glucose Positron Emission Tomography images were coregistered to a rat brain template and normalized from the total brain Positron Emission Tomography signal. Voxel-to-voxel analysis was performed using SPM8 software. Comparison of brain glucose metabolism between groups was then performed.Results: THN102 significantly increased regional brain glucose metabolism as it resulted in large clusters of 18F-2-fluoro-2-deoxy-D-glucose uptake localized in the cortex, striatum, and amygdala compared with control or drugs administered alone. These regions, highly involved in the regulation of sleep-wake cycle, emotions, and cognitive functions were hence quantitatively modulated by THN102.Conclusion: Data presented here provide the first evidence of a regional brain activation induced by THN102, currently being tested in a phase II clinical trial in narcoleptic patients.
Databáze: OpenAIRE
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