1,720,958 research outputs found

    The effects of social isolation and environmental modulation on the glutamatergic cortico-accumbens synaptic plasticity

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    Previous studies in our laboratory have highlighted the importance of the setting in which drug is taken. We used an in vivo animal model in which one group of rats is transferred to the self-administration (SA) chambers during the 3 hour test sessions (Non Resident rats) and a second group literally lives in the SA chambers (Resident rats). Using this model we have seen that the setting modulates heroin self-administration (Caprioli et al. 2008), the choice between heroin and cocaine (Caprioli et al., 2009), the relapse (Montanari et al., 2015), as well as the internal state of the rats (Avvisati et al., 2016). Also the neurobiological effects of heroin are a function of the setting as previously demonstrated (Paolone et al. 2007; Celentano et al. 2009) using in situ hybridization and immunohistochemistry experiments. Thus, in the present study we have hypothesized the setting may influence also the synaptic plasticity in the cortico-accumbens circuit, areas involved in the impaired ability of addicts to regulate drug seeking, taking and relapse (Jentsch and Taylor, 1999; Luscher and Malenka, 2011; Nestler 2001; Kalivas and Volkow, 2011; Kalivas and O’Brien, 2008; Kalivas et al., 2004; Self et al., 2004). We trained independent groups of rats self administering heroin (25μg/kg/infusion) and saline for 10 sessions (3 hour each). After 14 days of abstinence rats underwent a cue induced reinstatement test. We also exposed single housed rats (IH) to Residence and Non Residence condition and we compared these rats with grouped house rats (GH). Using ex vivo field recordings on parasagittal slice we found that Heroin SA Resident rats showed an impairment in the capability to induce LTP (fEPSP amplitude 140% of baseline) when compared to Heroin SA Non Resident rats (fEPSP amplitude about 160% of baseline). Moreover saline SA, as well, single housed rats showed an impairment in the capability to induce LTP (fEPSP amplitude about 120% of baseline) when compared with grouped house rats (fEPS amplitude about 160%). This suggests that 1) cortico-accumbens synaptic plasticity is impaired in isolated rats and 2) heroin produces a recovering in the LTP response in both Non Resident and Resident rats even if Resident rats showed a non complete LTP recovering maybe due to the more rewarding effect of the drug in this environment. Further elucidations on how drugs of abuse alter cortico-accumbens plasticity will be necessary for the development of new therapies especially studies based on the use of heroin administration since most of the articles in literature have used cocaine

    Context dependent effects of heroin self administration on nucleus accumbens synaptic plasticity

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    We have previously reported the setting of drug self-administration has a powerful influence on drug intake(Caprioli et al. 2008). Rats that lived in the self-administration (SA) chamber (ResidentRats) tended to self-administer more heroin than rats that were exposed to the SA chamber only during testing (NonResidentRats living in a distinct home cage). Also the neurobiological effects of heroin are a function of setting. In situ hybridization and immunohistochemistry experiments have shown that the effects of heroin on the expression of FosmRNA and Fos in the reward regions of the brain are very different in Resident vs. NonResidentRats (Paolone et al. 2007; Celentano et al. 2009). Fos is a transcription factor that is thought to be implicated in the early stages of drug-induced neuroplasticity. Thus, we hypothesized that the setting may influence heroin-induced long term plasticity.In the present study, we used ex vivo electrophysiological recordings to investigate the effects of heroin SA on long term cortico-accumbens synaptic plasticity as a function of setting. Both Resident and NonResident rats were trained to self-administer heroin (25μg/kg/infusion) for 10sessions (3h each).After 14 days of abstinence from heroin the rats were killed and their brains excised to obtain parasagittal slices for field recordings. We found that after tetanic stimulation, LTP was greater in NonResidentRats (fEPSP amplitude about 160% of baseline) than in ResidentRats (140% of baseline). This suggests that cortico-accumbens (presumably inhibitory) inputs are reduced when the rats self-administer heroin in their home environment relative to a non-home setting and may explain why ResidentRats tend self-administer more heroin than NonResidentRat

    Differential vulnerability to relapse into heroin versus cocaine-seeking as a function of setting

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    RATIONALE: Previous studies have shown that the effect of setting on drug-taking is substance specific in both humans and rats. In particular, we have shown that when the setting of drug self-administration (SA) coincides with the home environment of the rats (resident rats), the rats tend to prefer heroin to cocaine. The opposite was found in nonresident rats, for which the SA chambers represented a distinct environment. OBJECTIVES: The aim of the present study was to investigate the influence of setting on the ability of different doses of cocaine and heroin to prime cocaine- versus heroin-seeking in rats that had been trained to self-administer both drugs and had then undergone an extinction procedure. METHODS: Resident (N = 62) and nonresident (N = 63) rats with double-lumen intra-jugular catheters were trained to self-administer cocaine (400 μg/kg/infusion) and heroin (25 μg/kg/infusion) on alternate days for 10 consecutive daily sessions (3 h each). After the extinction phase, independent groups of rats were given a noncontingent intravenous infusion of heroin (25, 50, or 100 μg/kg) or cocaine (400, 800, or 1600 μg/kg), and drug-seeking was quantified by counting nonreinforced lever presses. RESULTS: All resident and nonresident rats acquired heroin and cocaine SA. However, cocaine primings reinstated cocaine-seeking only in nonresident rats, whereas heroin primings reinstated heroin-seeking only in resident rats. CONCLUSIONS: We report here that the susceptibility to relapse into drug-seeking behavior is drug-specific and setting-specific, confirming the crucial role played by drug, set, and setting interactions in drug addictio

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Intravenous self-administration of benzydamine, a non-steroidal anti-inflammatory drug with a central cannabinoidergic mechanism of action

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    Benzydamine (BZY) is a non-steroidal anti-inflammatory drug used for the topical treatment of inflammations of the oral and vaginal mucosae. Virtually nothing is known about the central pharmacological actions of BZY. Yet there are reports of voluntary systemic overdosage of BZY in drug addicts, resulting in a euphoric, hallucinatory state. In the present study, we investigated the reinforcing properties of BZY in a rat self-administration paradigm. We found that BZY has a powerful reinforcing effect and that this effect is greatly facilitated in animals that already had substance experience, having previously self-administered heroin and cocaine, indicating cross sensitization between BZY and other common drugs of abuse. We then assessed the effect of BZY on prelimbic cortex-to-nucleus accumbens glutamatergic transmission, using field recordings in rat parasagittal brain slices. BZY dose-dependently reduced both field excitatory post synaptic potential amplitude and paired pulse ratio, suggesting a presynaptic mechanism of action. Similarly to the in vivo paradigm, also the electrophysiological effects of BZY were potentiated in slices from animals that had undergone cocaine and heroin self-administration. Furthermore, BZY-induced Long Term Depression (LTD)-like responses in the prelimbic cortex-to-nucleus accumbens circuitry were significantly reduced in the presence of the CB1 receptor antagonist AM251. These findings provide firm evidence of the abuse liability of BZY and suggest a possible cannabinoidergic mechanism of action. Further research is needed in order to give insights into the molecular mechanism underlying BZY psychoactive and reinforcing effects, to better understand its abuse potential

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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