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

The first determination of Generalized Polarizabilities of the proton by a Virtual Compton Scattering experiment

Absolute differential cross sections for the reaction (e+p -> e+p+gamma) have been measured at a four-momentum transfer with virtuality Q^2=0.33 GeV^2 and polarization \epsilon = 0.62 in the range 33.6 to 111.5 MeV/c for the momentum of the outgoing photon in the photon-proton center of mass frame. The experiment has been performed with the high resolution spectrometers at the Mainz Microtron MAMI. From the photon angular distributions, two structure functions which are a linear combination of the generalized polarizabilities have been determined for the first time.Comment: 4 pages, 3 figure

bcl-2 expression is not associated with survival in metastatic cutaneous melanoma: A historical cohort study

<p>Abstract</p> <p>Background</p> <p>Programmed cell death (apoptosis) has been implicated in tumor development and may affect the metastatic potential of tumor cells. The role of bcl-2, a proto-oncogene that inhibits apoptosis, has been studied in several malignancies, including cutaneous melanoma (CM). The purpose of this study was to evaluate the immunohistochemical expression of bcl-2 in 35 regional lymph node, 28 subcutaneous and 17 visceral CM metastases, correlating the findings with patient survival.</p> <p>Methods</p> <p>In a historical cohort study patient survival was correlated with the expression of bcl-2 in regional lymph node, subcutaneous and visceral metastases of CM. Eighty slides containing surgical specimens from 50 patients diagnosed with stage III and IV CM, 28 male (56%) and 22 female (44%), were analyzed. Mean age at diagnosis was 43 years (16–74 years; median = 42 years). Mean Breslow depth was 5.01 mm (0.4–27.5 mm). The slides were submitted to immunohistochemical reaction using anti-bcl-2 monoclonal antibody and classified according to the degree of staining (< 5%; 5 to 50%; or > 50% of tumor cells stained). The relationship between bcl-2 protein expression and survival for each type of metastasis, gender and age at initial diagnosis was analyzed.</p> <p>Results</p> <p>Mean overall survival was 33.9 months after the diagnosis of the initial metastatic lesion (range: 0 to 131 months). Twenty-four out of 50 patients (48%) had died from CM by the end of the study period. bcl-2 expression was detected in 74.3, 85.7 and 82.4% of lymph node, subcutaneous and visceral metastases, respectively. After univariate and multivariate analyses, no correlation was found between positive bcl-2 expression and overall survival for the types of metastases evaluated.</p> <p>Conclusion</p> <p>The immunohistochemical expression of bcl-2 in metastasis alone is not a prognostic marker for CM.</p

Display of probability densities for data from a continuous distribution

Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201

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

Comparison between the transverse responses of the reactions C-12(e, e(') p)B-11 and C-12(gamma, p)B-11

A study of the reaction C-12(e,e'p)B-11 in parallel kinematics has been made for the missing-momentum region 25