Effects of Ketamine and Ketamine Metabolites on Evoked Striatal Dopamine Release, Dopamine Receptors, and Monoamine Transporters

Following administration at subanesthetic doses, (R,S)-ketamine (ketamine) induces rapid and robust relief from symptoms of depression in treatment-refractory depressed patients. Previous studies suggest that ketamine’s antidepressant properties involve enhancement of dopamine (DA) neurotransmission. Ketamine is rapidly metabolized to (2S,6S)- and (2R,6R)-hydroxynorketamine (HNK), which have antidepressant actions independent of N-methyl-d-aspartate glutamate receptor inhibition. These antidepressant actions of (2S,6S;2R,6R)-HNK, or other metabolites, as well as ketamine’s side effects, including abuse potential, may be related to direct effects on components of the dopaminergic (DAergic) system. Here, brain and blood distribution/clearance and pharmacodynamic analyses at DA receptors (D1–D5) and the DA, norepinephrine, and serotonin transporters were assessed for ketamine and its major metabolites (norketamine, dehydronorketamine, and HNKs). Additionally, we measured electrically evoked mesolimbic DA release and decay using fast-scan cyclic voltammetry following acute administration of subanesthetic doses of ketamine (2, 10, and 50 mg/kg, i.p.). Following ketamine injection, ketamine, norketamine, and multiple hydroxynorketamines were detected in the plasma and brain of mice. Dehydronorketamine was detectable in plasma, but concentrations were below detectable limits in the brain. Ketamine did not alter the magnitude or kinetics of evoked DA release in the nucleus accumbens in anesthetized mice. Neither ketamine’s enantiomers nor its metabolites had affinity for DA receptors or the DA, noradrenaline, and serotonin transporters (up to 10 μM). These results suggest that neither the side effects nor antidepressant actions of ketamine or ketamine metabolites are associated with direct effects on mesolimbic DAergic neurotransmission. Previously observed in vivo changes in DAergic neurotransmission following ketamine administration are likely indirect

Social and Hydrological Responses to Extreme Precipitations: An Interdisciplinary Strategy for Postflood Investigation

International audienceThis paper describes and illustrates a methodology to conduct postflood investigations based on interdisciplinary collaboration between social and physical scientists. The method, designed to explore the link between crisis behavioral response and hydrometeorological dynamics, aims at understanding the spatial and temporal capacities and constraints on human behaviors in fast-evolving hydrometeorological conditions. It builds on methods coming from both geosciences and transportations studies to complement existing post-flood field investigation methodology used by hydrometeorologists. The authors propose an interview framework, structured around a chronological guideline to allow people who experienced the flood firsthand to tell the stories of the circumstances in which their activities were affected during the flash flood. This paper applies the data collection method to the case of the 15 June 2010 flash flood event that killed 26 people in the Draguignan area (Var, France). As a first step, based on the collected narratives, an abductive approach allowed the identification of the possible factors influencing individual responses to flash floods. As a second step, behavioral responses were classified into categories of activities based on the respondents' narratives. Then, aspatial and temporal analysis of the sequences made of the categories of action to contextualize the set of coping responses with respect to local hydrometeorological conditions is proposed. During this event, the respondents mostly follow the pace of change in their local environmental conditions as the flash flood occurs, official flood anticipation being rather limited and based on a large-scale weather watch. Therefore, contextual factors appear as strongly influencing the individual's ability to cope with the event in such a situation

Comprendre les comportements face à un risque modéré d’inondation. Etude de cas dans le périurbain toulousain (Sud-Ouest de la France)

Les espaces urbanisés soumis à des risques modérés d’inondation pour les vies humaines sont souvent peu considérés dans les études sur la vulnérabilité aux risques naturels en dépit des enjeux qu’ils représentent en termes de gestion de crise. Comment les riverains y font-ils face au danger et quelles sont leurs « bonnes raisons » d’agir? A partir de l’étude socio-géographique de deux inondations récentes (2000 et 2003) dans la périphérie toulousaine (Sud-Ouest de la France), nous montrons que les caractéristiques de l’aléa dans les vallées étudiées influencent les représentations du risque et par conséquent les motivations à se protéger. Face au risque majeur, la vulnérabilité sociale se trouve ainsi augmentée. Pour améliorer la résilience des populations, il convient d’adapter la communication sur les risques: personnaliser l’information, améliorer la compréhension de l’événement vécu et mobiliser de nouvelles formes de médiation entre gestionnaires et riverains

Is Scotland a Westminster-style Majoritarian Democracy or a Scandinavian-style Consensus Democracy? A Comparison of Scotland, the UK and Sweden

Peer reviewedPostprin

Simulation hydrologique de crues éclairs à l'échelle régionale: échelle des signatures pour la vulnérabilité aux coupures de routes

International audienceThis work contributes to the evaluation of the dynamics of the human exposure during flash-flood events in the Mediterranean region. Understanding why and how the commuters modify their daily mobility in the Cévennes - Vivarais area (France) is the main objective of the study. To reach this objective, the methodology relies on three steps: i) evaluation of daily travel patterns, ii) reconstitution of road flooding events in the region based on hydrological simulation at regional scale in order to capture the temporality and the intensity of flood and iii) identification of the daily fluctuation of the exposition according to road flooding scenarios and the temporality of mobility patterns. This presentation focuses on step ii), i.e. the implementation of the physically based and non-calibrated hydrological model CVN (Anquetin et al., 2010; Braud et al., 2010; Vannier, PhD 2013) to retrieve the hydrological signatures of past flash-flood events in the Cévennes ¿ Vivarais region. Since the regional scale is investigated, the scales of the studied catchments range from few km2 to few hundreds of km2 where many catchments are ungauged. The model parameters are derived from available information about geology, land use, soil pedology. We found that information on soil was not reliable and that soil water holding capacity was generally underestimated due to the absence of information about altered geological layers. Vannier et al. (2013) regionalized the estimation of catchment-scale soil properties (soil water holding capacity and lateral hydraulic conductivity) by means of stream-flow recession analysis. The use of the corresponding retrieved parameters in the CVN model significantly improves the agreement between observed and simulated hydrological response in gauged catchments. It is therefore taken into account in the regional modeling strategy. Two past events (September 2007; October 2008) are analyzed in terms of temporality of road flooding. The scales of risk (time and location of the road flooding) are compared to observed data of road cuts. A sensitivity study to rainfall estimation investigates the signature of several rainfall products on the simulated discharges. These products are based on radar estimation and/or rain gauge records

Le programme HyMeX - connaissances et prévision des pluies intenses et crues rapides en région méditerranéenne

Conférence SHF « de la prévision des crues à la gestion de crise », Avignon, FRA, 14-/11/2018 - 16/11/2018National audienceLe programme international de recherche HyMeX (Hydrological cycle in the Mediterranean eXperiment, www.hymex.org), composante du chantier multi-organisme MISTRALS lancé pour 10 ans en 2010, a pour objectif de progresser dans la compréhension du cycle de l'eau en Méditerranée, et notamment d'améliorer les connaissances et la prévision des risques hydrométéorologiques. L'étude et la prévision des épisodes de pluies intenses et crues rapides qui affectent régulièrement le pourtour Méditerranéen sont au coeur du programme HyMeX. Après une présentation de la stratégie générale d'observations qui a combiné campagnes de mesures, renforcement d'observations pendant plusieurs automnes et collectes de données socio-hydrologiques après les évènements majeurs qu'a connu la région sur la période, une revue d'ensemble des avancées scientifiques réalisées depuis le lancement d'HyMeX est proposée tant en termes de connaissances et modélisation des épisodes méditerranéens de pluie intense et de leurs impacts, qu'en termes d'évaluation et amélioration des méthodes et systèmes de prévision, et plus particulièrement les systèmes de prévision d'ensemble hydrométéorologiques à courte échéance basés sur le modèle de prévision météorologique AROME de Météo-France