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

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

Across the Gap: Geochronological and Sedimentological Analyses from the Late Pleistocene-Holocene Sequence of Goda Buticha, Southeastern Ethiopia

Goda Buticha is a cave site near Dire Dawa in southeastern Ethiopia that contains an archaeological sequence sampling the late Pleistocene and Holocene of the region. The sedimentary sequence displays complex cultural, chronological and sedimentological histories that seem incongruent with one another. A first set of radiocarbon ages suggested a long sedimentological gap from the end of Marine Isotopic Stage (MIS) 3 to the mid-Holocene. Macroscopic observations suggest that the main sedimentological change does not coincide with the chronostratigraphic hiatus. The cultural sequence shows technological continuity with a late persistence of artifacts that are usually attributed to the Middle Stone Age into the younger parts of the stratigraphic sequence, yet become increasingly associated with lithic artifacts typically related to the Later Stone Age. While not a unique case, this combination of features is unusual in the Horn of Africa. In order to evaluate the possible implications of these observations, sedimentological analyses combined with optically stimulated luminescence (OSL) were conducted. The OSL data now extend the radiocarbon chronology up to 63 ± 7 ka; they also confirm the existence of the chronological gap between 24.8 ± 2.6 ka and 7.5 ± 0.3 ka. The sedimentological analyses suggest that the origin and mode of deposition were largely similar throughout the whole sequence, although the anthropic and faunal activities increased in the younger levels. Regional climatic records are used to support the sedimentological observations and interpretations. We discuss the implications of the sedimentological and dating analyses for understanding cultural processes in the region.This research benefited from funding of the National Geographic Society (http:// nationalgeographic.org/), grants # 8110-06 and 8510-08 (ZA), of the Wenner-Gren Foundation (http://www.wennergren.org/), grant # ICRG e 102, (ZA and DP), of the Hebrew University of Jerusalem (http://new.huji.ac.il/en) (EH), of the French National Research Agency (http://www.agence-nationale-recherche.fr), projects # ANR-09- JCJC-0123-01 (CT), # ANR-14-CE31-0023-03, and # ANR-10-LABX-52, of the Regional Priority Program « Heritage, Resources, Governance » (HEREGO, coordinated by the Institut de Recherche pour le Developpement) (DP), the Doctoral School of the Museum National d’Histoire Naturelle in Paris (France) and UMR CNRS 7194 (AL), the Smithsonian NMNH small grants, and the European Union’s Horizon 2020 research and innovation program under the Marie SklodowskaCurie grant (https://ec.europa.eu/programmes/ horizon2020/en/h2020-section/marie-sklodowskacurie-actions), agreement #655459. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Across the Gap: Geochronological and Sedimentological Analyses from the Late Pleistocene-Holocene Sequence of Goda Buticha, Southeastern Ethiopia

Goda Buticha is a cave site near Dire Dawa in southeastern Ethiopia that contains an archaeological sequence sampling the late Pleistocene and Holocene of the region. The sedimentary sequence displays complex cultural, chronological and sedimentological histories that seem incongruent with one another. A first set of radiocarbon ages suggested a long sedimentological gap from the end of Marine Isotopic Stage (MIS) 3 to the mid-Holocene. Macroscopic observations suggest that the main sedimentological change does not coincide with the chronostratigraphic hiatus. The cultural sequence shows technological continuity with a late persistence of artifacts that are usually attributed to the Middle Stone Age into the younger parts of the stratigraphic sequence, yet become increasingly associated with lithic artifacts typically related to the Later Stone Age. While not a unique case, this combination of features is unusual in the Horn of Africa. In order to evaluate the possible implications of these observations, sedimentological analyses combined with optically stimulated luminescence (OSL) were conducted. The OSL data now extend the radiocarbon chronology up to 63 ± 7 ka; they also confirm the existence of the chronological gap between 24.8 ± 2.6 ka and 7.5 ± 0.3 ka. The sedimentological analyses suggest that the origin and mode of deposition were largely similar throughout the whole sequence, although the anthropic and faunal activities increased in the younger levels. Regional climatic records are used to support the sedimentological observations and interpretations. We discuss the implications of the sedimentological and dating analyses for understanding cultural processes in the region.This research benefited from funding of the National Geographic Society (http:// nationalgeographic.org/), grants # 8110-06 and 8510-08 (ZA), of the Wenner-Gren Foundation (http://www.wennergren.org/), grant # ICRG e 102, (ZA and DP), of the Hebrew University of Jerusalem (http://new.huji.ac.il/en) (EH), of the French National Research Agency (http://www.agence-nationale-recherche.fr), projects # ANR-09- JCJC-0123-01 (CT), # ANR-14-CE31-0023-03, and # ANR-10-LABX-52, of the Regional Priority Program « Heritage, Resources, Governance » (HEREGO, coordinated by the Institut de Recherche pour le Developpement) (DP), the Doctoral School of the Museum National d’Histoire Naturelle in Paris (France) and UMR CNRS 7194 (AL), the Smithsonian NMNH small grants, and the European Union’s Horizon 2020 research and innovation program under the Marie SklodowskaCurie grant (https://ec.europa.eu/programmes/ horizon2020/en/h2020-section/marie-sklodowskacurie-actions), agreement #655459. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Research Data supporting "Saccharin fading is not required for the acquisition of alcohol self-administration, and can alter the dynamics of cue-alcohol memory reconsolidation"

The shared files contain the data all behavioural data described in the paper. Briefly, rats were trained to orally self-administer 10% ethanol by lever pressing to receive the ethanol reinforcer. Half of the rats had been previously exposed to sweetened ethanol in the saccharin fading procedure, while half of the rats were naive. All animals were assessed for their ability to acquire self-administration of oral ethanol in the presence of a pavlovian light cue that was paired with alcohol delivery. 72hrs after the end of training, all rats were reminded of the cue-ethanol memory in a brief 'memory reactivation' session, prior to which they received injections of the NMDA receptor antagonist MK-801 or vehicle. 72hrs after this session, all rats were tested for the capacity of the previously alcohol-paired cue to support cue-induced reinstatement of ethanol-seeking. Three weeks after this test, all animals were given three 'rebaselining' sessions on ethanol self-administration, before undergoing an extinction session in which responding on the lever produced neither the cue, nor the ethanol reinforcer. 24hrs after this, they underwent another cue-induced reinstatement test. Finally, all rats were assessed for their voluntary ethanol consumption and preference using the 2-bottle choice procedure. Data from all of the above stages of the experiment are reported in the Excel spreadsheets, with accompanying metadata in a Word document

Hydrodynamic characterization of the exopolysaccharide from the halophilic cyanobacterium Aphanothece halophytica GR02: A comparison with xanthan

A bacterial exopolysaccharide from Aphanothece halophytica GR02 (AH-EPS) solubilized in buffered 1 M guanidine hydrochloride, GuHCl was studied using capillary viscometry, double gap viscometry, sedimentation velocity and sedimentation equilibrium using analytical ultracentrifugation. Results from capillary viscometry indicate that the exopolysaccharide is xanthan-like in its shear thinning properties. This was confirmed by double gap viscometry. Sedimentation velocity (distribution of apparent sedimentation coefficients) confirmed that the AH-EPS solution was reasonably homogeneous and a hyper-sharp boundary indicated that AH-EPS is a rigid/extra-rigid rod type polysaccharide. Sedimentation equilibrium confirmed the high molecular weight indicated by viscosity measurements. In order to ascertain whether the solution physical properties of AH-EPS are xanthan-like under the conditions studied, all the above experiments were repeated on a similarly treated xanthan solution in the same solvent. Results indicate that AH-EPS is indeed xanthan-like in its physical properties at least in the system studied. Xanthan properties in GuHCl do not appear too different from those studied in more traditional solvents

Le site du Ranc-Pointu no. 2 à Saint-Martin-d’Ardèche : Une occupation du Paléolithique moyen ancien dans le Sud-Est de la France = The site of Ranc-Pointu No. 2 at Saint-Martin-d’Ardèche: An early Middle Palaeolithic occupation in southeastern France?

International audienc

Les premiers Hommes anatomiquement modernes du sud-est de l’Europe: apport du site de Buran-Kaya III (Crimée)

International audienc

Les premiers hommes anatomiquement modernes du Sud-Est de l’Europe. Apport du site de Buran-Kaya III (Crimée)

International audienceThe arrival of modern humans into Europe, their dispersal and their potential interactions with Neanderthals are still in debate. Whereas the first appearance of anatomically modern humans in Western Europe seems to be well understood, the situation is quite different for Eastern Europe, where data are more scarce. The Buran-Kaya III site in Crimea is of key importance to understand the colonization of Europe by anatomically modern humans and their potential contemporaneity with the last Neanderthal occupations. The new radiocarbon dated sequence shows that no Neanderthal settlement existed after 39 ka cal BP and casts doubt on the survival, as previously proposed, of Neanderthal refuge zones in Crimea 28 ka BP ago (34-32 ka cal BP). The human remains from Buran-Kaya III, directly dated to 32450 +250/-230 BP (layer 6-2) and 31900+/-220 BP (layer 6-1) (37.1-35.7 ka cal BP and 36.3-35.2 cal BP respectively), represent some of the oldest evidence of anatomically modern humans in Europe in a unique welldocumented archaeological context (Gravettian). Furthermore, the specimens from layer 6-1 represent the oldest Upper Palaeolithic modern humans from Eastern Europe with evidence of post-mortem treatment of the dead.L’arrivée des premières populations d’hommes anatomiquement modernes en Europe et leurs interactions avec les Néandertaliens font l’objet de nombreux débats. Si cette histoire semble bien comprise en Europe occidentale, il en est différemment en Europe orientale où la documentation est plus parcellaire. Le site de Buran-Kaya III, en Crimée, apparaît comme un site majeur grâce à l’apport de nouvelles données chronologiques relatives aux dernières occupations néandertaliennes, et à la présence de restes attribués aux hommes anatomiquement modernes directement datés à 32450 +250/-230 BP (niveau 6-2) et 31900+/-220 BP (niveau 6-1) (37,1-35,7 ka cal BP and 36,3-35,2 ka cal BP respectivement). Les nouvelles datations radiocarbones montrent que les populations néandertaliennes n’étaient plus présentes en Crimée après 39 ka cal BP et remettent en question l’existence, qui était proposée jusqu’à alors, d’une zone refuge pour ces populations en Crimée il y a 28 ka BP (34-32 ka cal BP). Par ailleurs, les restes humains de Buran-Kaya III sont parmi les plus anciens hommes anatomiquement modernes d’Europe orientale et, fait exceptionnel, dans un contexte culturel bien documenté (techno-complexe gravettien). Les individus de la couche 6-1 sont, en outre, les plus anciens hommes modernes du Paléolithique supérieur d’Europe orientale à témoigner d’un traitement post-mortem complexe des défunts