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

Structural effects of anomalous current densities on manganese hexacyanoferrate for Li-ion batteries

A battery management system (BMS) plays a pivotal role in providing optimal performance of lithium-ion batteries (LIBs). However, the eventual malfunction of the BMS may lead to safety hazards or reduce the remaining useful life of LIBs. Manganese hexacyanoferrate (MnHCF) was employed as the positive electrode material in a Li-ion half-cell and subjected to five cycles at high current densities (10 A gMnHCF−1) and to discharge at 0.1 A gMnHCF−1, instead of classical charge/discharge cycling with initial positive polarization at 0.01 A gMnHCF−1, to simulate a current sensor malfunctioning and to evaluate the electrochemical and structural effects on MnHCF. The operando set of spectra at the Mn and Fe K-edges was further analyzed through multivariate curve resolution analysis with an alternating least squares algorithm (MCR–ALS) and extended X-ray absorption fine structure (EXAFS) spectroscopy to investigate the structural modifications arising during cycling after the applied electrochemical protocol. The coulombic efficiency in the first cycle was dramatically affected; however, the local structural environment around each photo absorber recovered during charging. The identification of an additional spectral contribution in the electrochemical process was achieved through MCR-ALS analysis, and the Mn-local asymmetry was thoroughly explored via EXAFS analysis

From impulses to maladaptive actions: the insula is a neurobiological gate for the development of compulsive behavior.

Impulsivity is an endophenotype of vulnerability for compulsive behaviors. However, the neural mechanisms whereby impulsivity facilitates the development of compulsive disorders, such as addiction or obsessive compulsive disorder, remain unknown. We first investigated, in rats, anatomical and functional correlates of impulsivity in the anterior insular (AI) cortex by measuring both the thickness of, and cellular plasticity markers in, the AI with magnetic resonance imaging and in situ hybridization of the immediate early gene zif268, respectively. We then investigated the influence of bilateral AI cortex lesions on the high impulsivity trait, as measured in the five-choice serial reaction time task (5-CSRTT), and the associated propensity to develop compulsivity as measured by high drinking levels in a schedule-induced polydipsia procedure (SIP). We demonstrate that the AI cortex causally contributes to individual vulnerability to impulsive-compulsive behavior in rats. Motor impulsivity, as measured by premature responses in the 5-CSRTT, was shown to correlate with the thinness of the anterior region of the insular cortex, in which highly impulsive (HI) rats expressed lower zif268 mRNA levels. Lesions of AI reduced impulsive behavior in HI rats, which were also highly susceptible to develop compulsive behavior as measured in a SIP procedure. AI lesions also attenuated both the development and the expression of SIP. This study thus identifies the AI as a novel neural substrate of maladaptive impulse control mechanisms that may facilitate the development of compulsive disorders.This research was carried-out within the Department of Psychology and the Department of Pharmacology of the University of Cambridge as well as the INSERM AVENIR team Psychobiology of Compulsive Disorders of the University of Poitiers. It was supported by an INSERM AVENIR grant and a FYSSEN foundation grant to DB. 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 INSERM. BJE was supported by the United Kingdom Medical Research Council (MRC) Grant 9536855.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/mp.2015.14

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

Substantial improvements not seen in health behaviors following corner store conversions in two Latino food swamps.

BackgroundThe effectiveness of food retail interventions is largely undetermined, yet substantial investments have been made to improve access to healthy foods in food deserts and swamps via grocery and corner store interventions. This study evaluated the effects of corner store conversions in East Los Angeles and Boyle Heights, California on perceived accessibility of healthy foods, perceptions of corner stores, store patronage, food purchasing, and eating behaviors.MethodsHousehold data (n = 1686) were collected at baseline and 12- to 24-months post-intervention among residents surrounding eight stores, three of which implemented a multi-faceted intervention and five of which were comparisons. Bivariate analyses and logistic and linear regressions were employed to assess differences in time, treatment, and the interaction between time and treatment to determine the effectiveness of this intervention.ResultsImprovements were found in perceived healthy food accessibility and perceptions of corner stores. No changes were found, however, in store patronage, purchasing, or consumption of fruits and vegetables.ConclusionsResults suggest limited effectiveness of food retail interventions on improving health behaviors. Future research should focus on other strategies to reduce community-level obesity

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

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)