N-acetylcysteine Facilitates Self-Imposed Abstinence After Escalation of Cocaine Intake.

BACKGROUND: N-acetylcysteine (NAC) has been suggested to prevent relapse to cocaine seeking. However, the psychological processes underlying its potential therapeutic benefit remain largely unknown. METHODS: We investigated the hallmark features of addiction that were influenced by chronic NAC treatment in rats given extended access to cocaine: escalation, motivation, self-imposed abstinence in the face of punishment, or propensity to relapse. For this, Sprague Dawley rats were given access either to 1 hour (short access) or 6 hours (long access [LgA]) self-administration (SA) sessions until LgA rats displayed a robust escalation. Rats then received daily saline or NAC (60 mg/kg, intraperitoneal) treatment and were tested under a progressive ratio and several consecutive sessions in which lever presses were punished by mild electric foot shocks. RESULTS: NAC increased the sensitivity to punishment in LgA rats only, thereby promoting abstinence. Following the cessation of punishment, NAC-treated LgA rats failed to recover fully their prepunishment cocaine intake levels and resumed cocaine SA at a lower rate than short access and vehicle-treated LgA rats. However, NAC altered neither the escalation of SA nor the motivation for cocaine. At the neurobiological level, NAC reversed cocaine-induced decreases in the glutamate type 1 transporter observed in both the nucleus accumbens and the dorsolateral striatum. NAC also increased the expression of Zif268 in the nucleus accumbens and dorsolateral striatum of LgA rats. CONCLUSIONS: Our results indicate that NAC contributes to the restoration of control over cocaine SA following adverse consequences, an effect associated with plasticity mechanisms in both the ventral and dorsolateral striatum.This research was supported by a French Institute of Health and Medical Research Avenir and an ANR12 SAMA00201 Grant (to DB) as well as a Newton Trust/Cambridge University Grant (to DB). BJE and JEM are supported by a Medical Research Council (G9536855, G0701500) Grant to BJE and by a joint award from the Medical Research Council and Wellcome Trust in support of the Behavioral and Clinical Neuroscience Institute at Cambridge University

Les levures d'un chai du Mâconnais

 The yeasts of a Mâconnais wineryThe yeast populations of the various parts of a Mâconnais winery have been analysed from a taxonomy and biology point of view. 14 species have been isolated from the cernent vats used for red and white wine making, on the horizontal wine-presses with wooden and plastics laths, on the walls and ground of the winery and on the bottling apparatus. The qualitative and quantitative distribution of the species has been studied. The dominant species was Saccharomyces cerevisiae. Hansenula anomala and Pichia membranaefaciens were also frequent. Some species have newly been revealed in this habitat: Hansenula subpelliculosa, Saccharomyces pretoriensis, Cryptococcus infirmo-miniatus, Cr. laurentii and Aureobasidium pullulans

Recherches sur la répartition des levures à la surface de la grappe de raisin

Les recherches entreprises sur l'écologie des Levures dans le vignoble ont conduit à étudier au microscope électronique à balayage: (1) les divers éléments de la grappe de raisin, rafle, pédicelle, baie; (2) la répartition des Levures à leur surface. L'étude de la morphologie inframicroscopique de la rafle et du pédicelle ainsi que les travaux d'autres auteurs sur la baie de raisin permettent: (1) de mieux connaitre le substrat sur lequel sont deposées les cellules de Levures; (2) d'entreprendre l'etude des conditions écologiques de survie et de prolifération des Levures à la surface de la grappe de raisin.Nos observations montrent que les Levures ne sont pas uniformément réparties sur toute la grappe:a) la rafle semble en être totalement dépourvue;b) le bourrelet du pédicelle est abondamment colonisé par les cellules de Levures;c) sur la baie, le stomate et son auréole péristomatique sont une zone privilégiée pour la multiplication des Levures.Il apparait nettement que les Levures sont abondantes dans les régions présentant des cassures superficielles des tissus où peuvent se produire des sécrétions. Contrairement aux Levures isolées à la surface de la eire cuticulaire de l'épiderme, les cellules engluées dans des sécrétions ont une multiplication végétative intense. Ces observations permettent d'affiner les méthodes actuellement utilisées pour l'isolement de la microflore liée aux grappes de raisin.Untersuchungen über die Verteilung der Hefen auf der Oberfläche der WeintraubeIm Rahmen einer ökologischen Bearbeitung der Hefen in Rebanlagen wurden mit Hilfe des Rasterelektronenmikroskopes die verschiedenen Teile der Traube - Traubenachse mit Seitenästen, Beerenstiele und Beeren - sowie die Verteilung der Hefen auf deren Oberfläche untersucht. In Verbindung mit den Arbeiten anderer Autoren über die Beere vermitteln die morphologischen Untersuchungen im ultramikroskopischen Bereich eine bessere Kenntnis des Substrates, auf dem die Hefezellen vorkommen, sowie das Verständnis für die ökologischen Bedingungen, unter denen die Hefen auf der Weintraube leben und sich vermehren können. Die vorliegenden Beobachtungen zeigen, daß sich die Hefen nicht gleichmäßig über die ganze Weintraube verteilen: Die Traubenachse mit ihren Verzweigungen scheint vollkommen frei von Hefen zu sein, während das Fruchtpolster der Beerenstiele dicht mit Hefen besiedelt ist. Auf den Beeren sind die Stomata und die peristomatischen Bezirke bevorzugte Zonen für die Vermehrung der Hefen. Auffällig viele Hefen lassen sich im Bereich von Oberflächenrissen nachweisen, aus denen Zellsaft ausgetreten ist. Die hierin eingeschlossenen Hefen zeigen - im Gegensatz zu den Hefen, die von der Wachsschicht der Beerenschale isoliert wurden - eine besonders intensive vegetative Vermehrung. Die mitgeteilten Beobachtungen erlauben es, die gegenwärtig angewandten Methoden zur Isolierung der Mikroflora auf Weintrauben zu verfeinern

Heat Conduction in κ\kappa-(BEDT-TTF)2_2Cu(NCS)2_2

The first study of thermal conductivity, $\kappa$, in a quasi-two-dimensional organic superconductor of the $\kappa$-(BEDT-TTF)$_2$X family reveals features analogous to those already observed in the cuprates. The onset of superconductivity is associated with a sudden increase in $\kappa$ which can be suppressed by the application of a moderate magnetic field. At low temperatures, a finite linear term - due to a residual electronic contribution- was resolved. The magnitude of this term is close to what is predicted by the theory of transport in unconventional superconductors.Comment: 5 pages, 4 figures include

Angular momentum spatial distribution symmetry breaking in Rb by an external magnetic field

Excited state angular momentum alignment -- orientation conversion for atoms with hyperfine structure in presence of an external magnetic field is investigated. Transversal orientation in these conditions is reported for the first time. This phenomenon occurs under Paschen Back conditions at intermediate magnetic field strength. Weak radiation from a linearly polarized diode laser is used to excite Rb atoms in a cell. The laser beam is polarized at an angle of pi/4 with respect to the external magnetic field direction. Ground state hyperfine levels of the 5S_1/2 state are resolved using laser-induced fluorescence spectroscopy under conditions for which all excited 5P_3/2 state hyperfine components are excited simultaneously. Circularly polarized fluorescence is observed to be emitted in the direction perpendicular to both to the direction of the magnetic field B and direction of the light polarization E. The obtained circularity is shown to be in quantitative agreement with theoretical predictions.Comment: Accepted for publication in Phys. Rev.

Genetic engineering of the β-oxidation pathway in the yeast Yarrowia lipolytica to increase the production of aroma compounds

peer reviewedThe yeast Yarrowia lipolytica possesses five acyl-CoA oxidases (Aox1p to 5), the enzyme catalysing the first reaction of β-oxidation. The understanding of the specific role of each acyl-CoA oxidase is important to construct a yeast strain growing at a good rate and able to produce without degrading the aroma compound γ-decalactone. In this study we observed that Aox4p exhibits a slight activity on a broad spectrum of substrates and that it is involved in lactone degradation. We constructed a strain lacking this activity. Its growth was only slightly altered and it produced 10 times more lactone than the wild type in 48h. © 2004 Elsevier B.V. All rights reserved

High locomotor reactivity to novelty is associated with an increased propensity to choose saccharin over cocaine: new insights into the vulnerability to addiction.

Drug addiction is associated with a relative devaluation of natural or socially-valued reinforcers that are unable to divert addicts from seeking and consuming the drug. Before protracted drug exposure, most rats prefer natural rewards, such as saccharin, over cocaine. However, a subpopulation of animals prefer cocaine over natural rewards and are thought to be vulnerable to addiction. Specific behavioral traits have been associated with different dimensions of drug addiction. For example, anxiety predicts loss of control over drug intake whereas sensation seeking and sign-tracking are markers of a greater sensitivity to the rewarding properties of the drug. However, how these behavioral traits predict the disinterest for natural reinforcers remains unknown. In a population of rats, we identified sensation seekers (HR) on the basis of elevated novelty-induced locomotor reactivity, high anxious rats (HA) based on the propensity to avoid open arms in an elevated-plus maze and sign-trackers (ST) that are prone to approach, and interaction with, reward-associated stimuli. Rats were then tested on their preference for saccharin over cocaine in a discrete-trial choice procedure. We show that HR rats display a greater preference for saccharin over cocaine compared with ST and HA whereas the motivation for the drug was comparable between the three groups. The present data suggest that high locomotor reactivity to novelty, or sensation seeking, by predisposing to an increased choice toward non-drug rewards at early stages of drug use history, may prevent the establishment of chronic cocaine use.This work was funded by an INSERM AVENIR and Agence Nationale de la Recherche (ANR) ANR12 SAMA00201 grant to DB, the région Poitou-Charentes, an AXA research fund fellowship to ABR, and a Ministère de la Recherche et de la Technologie grant to NV. AM was supported by the Behavioural and Clinical Neuroscience Institute of Cambridge.This is the accepted manuscript of a paper published in Neuropsychopharmacology (2015) 40, 577–589; doi:10.1038/npp.2014.204; published online 17 September 2014

Coexistence of Singlet and Triplet Attractive Channels in the Pairing Interactions Mediated by Antiferromagnetic Fluctuations

We propose a phase diagram of quasi-low-dimensional type II superconductors in parallel magnetic fields, when antiferromagnetic fluctuations contribute to the pairing interactions. We point out that pairing interactions mediated by antiferromagnetic fluctuations necessarily include both singlet channels and triplet channels as attractive interactions. Usually, a singlet pairing is favored at zero field, but a triplet pairing occurs at high fields where the singlet pairing is suppressed by the Pauli paramagnetic pair-breaking effect. As a result, the critical field increases divergently at low temperatures. A possible relation to experimental phase diagrams of a quasi-one-dimensional organic superconductor is briefly discussed. We also discuss a possibility that a triplet superconductivity is observed even at zero field.Comment: 4 pages, 1 figure (Latex, revtex.sty, epsf.sty

Bidirectional regulation over the development and expression of loss of control over cocaine intake by the anterior insula

$\textbf{RATIONALE}$: Increasing evidence suggests that the anterior insular cortex (AIC) plays a major role in cocaine addiction, being implicated in both impaired insight and associated decision-making and also craving and relapse. However, the nature of the involvement of the insula in the development and maintenance of cocaine addiction remains unknown, thereby limiting our understanding of its causal role in addiction. We therefore investigated whether pre- and post-training bilateral lesions of the AIC differentially influenced the development and the expression of the escalation of cocaine self-administration during extended access to the drug. $\textbf{METHODS}$: In a series of experiments, Sprague Dawley rats received bilateral excitotoxic lesions of the AIC either prior to, or after 3 weeks of training under 12-h extended self-administration conditions, which are known to promote a robust escalation of intake. We also investigated the influence of AIC lesions on anxiety, as measured in an elevated plus maze and sensitivity to conditioned stimuli (CS)- or drug-induced reinstatement of an extinguished instrumental response. $\textbf{RESULTS}$: Whereas, post-escalation lesions of the AIC, as anticipated, restored control over cocaine intake and prevented drug-induced reinstatement, pre-training lesions resulted in a facilitation of the development of loss of control with no influence over the acquisition of cocaine self-administration or anxiety. $\textbf{CONCLUSIONS}$: AIC lesions differentially affect the development and maintenance of the loss of control over cocaine intake, suggesting that the nature of the contribution of cocaine-associated interoceptive mechanisms changes over the course of escalation and may represent an important component of addiction.This was supported by an INSERM AVENIR grant and a FYSSEN foundation grant to DB. PJC is supported by a Banting post-doctoral fellowship. MLD was supported by a PhD fellowship from the Fondation pour la Recherche Médicale (FRM) and ABR was supported by a post-doctoral fellowship from the AXA Research Fund. DB and BJE are supported by a joint programme grant from the MRC (RG82507) and a Leverhulme Trust grant (DB) (RG83473)