520. INCREASE OF THE AMPA-EVOKED RESPONSE IN PREFRONTAL CORTEX PYRAMIDAL NEURONS FOLLOWING ACUTE ADMINISTRATION OF KETAMINE AND S-KETAMINE IN RATS
Notice bibliographique
Résumé
Abstract Background Low dose ketamine has been shown, in animal studies, to enhance firing activity of norepinephrine neurons in the locus coeruleus, and burst as well as population activity of dopamine neurons in the ventral tegmental area [1]. These brainstem monoamine nuclei densely innervate the PFC, where clinical studies have shown a facilitation of glutamatergic neurotransmission in the PFC by a single injection of ketamine [2]. Aims & Objectives Due to reciprocal interactions between PFC glutamate neurons and monoamine neurons and their key role in the neurocircuitry of depression, the present electrophysiological study was aimed at investigating whether a single dose of ketamine has an effect on the AMPA- and NMDA-evoked responsiveness of PFC pyramidal neurons. Method Experiments were carried out on male Sprague Dawley rats weighing 275-300 g at the time of the experiments. Rats were anesthetized with chloral hydrate (400 mg/kg; ip) and mounted on a stereotaxic frame. Extracellular recordings of glutamate pyramidal neurons in the medial prefrontal cortex (mPFC) were carried out with five-barreled glass micropipettes. The central barrel used for the unitary recording was filled with a 2 M NaCl solution, and the impedance of these electrodes ranged from 2 to 4 MΩ. mPFC pyramidal neurons were identified using previously described criteria, and the responsiveness of these neurons to AMPA and NMDA applications by iontophoresis was assessed prior to and starting 30 minutes to 2 hours following administration of studied compounds. Results Despite mPFC pyramidal neurons displaying no change in their responsiveness to iontophoretically applied NMDA, an increase in responsiveness to iontophoretically applied AMPA was observed 30 minutes following ketamine and its enantiomer S-ketamine administration (10 mg/kg; two-Way repeated measures ANOVA, p < 0.001), when compared to saline treated rats. However, R-ketamine and the NMDA receptor GluN2B subunit antagonist ifenprodil have no effect on the responsiveness to AMPA and NMDA in mPFC pyramidal neurons compared to saline administered rats. Discussion & Conclusions Although both R-ketamine and ifenprodil were shown to have an antidepressant-like effect in the forced swim test [3,4], they do not seem to increase AMPA-induced response in the PFC, unlike racemic and S-ketamine. However, the increase in AMPA-induced response might constitute a common factor underlining the antidepressant-like effects of ketamine and S-ketamine. Such an increase coincides with an enhancement in expression of GluA1 subunit of AMPA receptors in the PFC in rat [5]. This is line with clinical studies showing that an increase in glucose metabolism, measured by 18F-FDG positron-emission tomography, suggesting an involvement of facilitation of glutamatergic neurotransmission in the PFC, which was correlated with the rapid antidepressant effect of low-dose of racemic ketamine [2].
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».