MicroPET imaging of 5-HT1A receptors in rat brain: a test-retest [18F]MPPF study

Purpose: Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [18F]MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine1A (5-HT1A) receptors in different regions of animal and human brain, including that of 5-HT1A autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems). Methods: Scans from isoflurane-anaesthetised rats (n = 18, including six test-retest) were co-registered with magnetic resonance imaging data, and binding potential, blood to plasma ratio and radiotracer efflux were estimated according to a simplified reference tissue model. Results: Values of binding potential for hippocampus (1.2), entorhinal cortex (1.1), septum (1.1), medial prefrontal cortex (1.0), amygdala (0.8), raphe nuclei (0.6), paraventricular hypothalamic nucleus (0.5) and raphe obscurus (0.5) were comparable to those previously measured with PET in cats, non-human primates or humans. Test-retest variability was in the order of 10% in the larger brain regions (hippocampus, medial prefrontal and entorhinal cortex) and less than 20% in small nuclei such as the septum and the paraventricular hypothalamic, basolateral amygdaloid and raphe nuclei. Conclusions: MicroPET brain imaging of 5-HT1A receptors with [18F]MPPF thus represents a promising avenue for investigating 5-HT1A receptor function in ra

MicroPET imaging of 5-HT1A receptors in rat brain: a test-retest [F-18]MPPF study

Purpose Earlier studies have shown that positron emission tomography (PET) imaging with the radioligand [F-18] MPPF allows for measuring the binding potential of serotonin 5-hydroxytryptamine(1A) (5-HT1A) receptors in different regions of animal and human brain, including that of 5-HT1A autoreceptors in the raphe nuclei. In the present study, we sought to determine if such data could be obtained in rat, with a microPET (R4, Concorde Microsystems)

Données nouvelles sur les innervations cholinergiques de l'hippocampe et du néostriatum et sur leur ultrastructure au cours du développement

Thèse numérisée par la Direction des bibliothèques de l'Université de Montréal

In vivo biased agonism at 5-HT1A receptors: characterisation by simultaneous PET/MR imaging

International audienceIn neuropharmacology, the recent concept of 'biased agonism' denotes the capacity of certain agonists to target-specific intracellular pathways of a given receptor in specific brain areas. In the context of serotonin pharmacotherapy, 5-HT1A receptor-biased agonists could be of great interest in several neuropsychiatric disorders. The aim of this study was to determine whether biased agonists could be differentiated in terms of regional targeting by use of simultaneous functional magnetic resonance imaging (fMRI) and positron emission tomography (PET) brain imaging. We compared two 5-HT1A-biased agonists, NLX-112 and NLX-101, injected at three different doses in anaesthetised cats (n = 4). PET imaging was acquired for 90 min after bolus administration followed by constant infusion of the 5-HT1A radiotracer, [18F]MPPF. Drug occupancy was evaluated after injection at  50 min and BOLD fMRI was simultaneously acquired to evaluate subsequent brain activation patterns. 5-HT1A receptor occupancy was found to be dose-dependent for both agonists, but differed in magnitude and spatial distribution at equal doses with distinct BOLD patterns. Functional connectivity, as measured by BOLD signal temporal correlations between regions, was also differently modified by NLX-112 or NLX-101. Voxel-based correlation analyses between PET and fMRI suggested that NLX-112 stimulates both 5-HT1A autoreceptors and post-synaptic receptors, whereas NLX-101 preferentially stimulates post-synaptic cortical receptors. In cingulate cortex, the agonists induced opposite BOLD signal changes in response to receptor occupancy. These data constitute the first simultaneous exploration of 5-HT1A occupancy and its consequences in terms of brain activation, and demonstrates differential signalling by two 5-HT1A-biased agonists. Combined PET/fMRI represents a powerful tool in neuropharmacology, and opens new ways to address the concept of biased agonism by translational approaches

CHANSONS DE PARIS (Vol. 5)

Titre uniforme : [Zon... Zon... Zon]Titre uniforme : [L'air de Paris]Comprend : SI JE N'AVAIS PLUS / Ch. AZNAVOUR ; Charles AZNAVOUR accompagné par Jean LECCIA et son orchestre - TOI, LES LARMES AUX YEUX / H. DECKER et M. VENDOME ; Virginie RENO accompagnée par Tito FUGGI et son orchestre - L'AIR DE PARIS / M. HEYRAL et F. LEMARQUE ; Michèle MATEY accompagnée par le MUSETTE de Loulou LEGRAN - PARIS S'EVEILLE LA NUIT / R. LUCCHESI et J. PLANTE ; les QUATRE de PARIS et l'Orchestre dir. Roger LUCCHESI - LE BAL DES TRUANDS / G. GARVARENTZ et C. NICOLAS ; Aïda AZNAVOUR accompagnée par Tito FUGGI et son Orchestre - ZON ZON / J. DATIN - M. VIDALIN ; Michèle ARNAUD accompagnée par François MARLHY et son orchestre - LE MOIS DES MARIS / J. ESTEREL et J. VIGOUROUX ; Jacques ESTEREL accompagné par Jacques LASRY - MOZART AVEC NOUS / arr. de Alain GORAGUER sur la musique de MOZART - Par. de Boris VIAN et Georges PRADET ; Denise BENOIT accompagnée par François RAUBER et son orchestre - ALORS, RACONTE / G. BECAUD - BROUSSOL ; les QUAT' JEUDIS au pianoYvonne SCHMITT - QU'ON EST BIEN / Guy BEART ; Anny FRATELLINI accompagnée par Raymond FOL et son orchestreBnF-Partenariats, Collection sonore - BelieveContient une table des matière