1,720,972 research outputs found

    Increase of dopamine and norepinephrine release in the bed nucleus of stria terminalis: a common feature of antidepressants?

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    The bed nucleus of stria teminalis (BNST) is an area that is considered part of the extended amygdala, a complex involved in the acquisition and expression of emotions. BNST, is richly innervated by monoamines, sends projections back to monoamine neurons and is considered a relay station in mediating the activation stress response through a strict relationship with the hypothalamic-pituitary-adrenocortical axis (HPA). On the other hand chronic stress is considered a risk factor for developing depression. Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. Since the systemic administration of reboxetine, a selective norepinephrine transporter (NET) blocker increases the extracellular concentration (output) of norepinephrine (NE) but also of dopamine (DA) in the BNST, it is conceivable that catecholamine transmission in BNST could be involved in the mechanism of action of antidepressants. The aim of this study was to characterize the acute effect of antidepressants belonging either to the NET blockers category or to the 5-HT reuptake blockers category (SSRI) on DA and NE ouput in the BNST, assayed through the in vivo microdialysis technique. The results obtained show that all the tested antidepressants (5 to 20 mg/kg i.p.) increased, dose dependently, NE and DA in the BNST. In particular, the increase reported for NE and DA respectively in % over basal were were as follows: desipramine, 239 and 137; reboxetine 185 and 128; imipramine 512 and 359; citalopram 95 and 122; fluoxetine 122 and 68; bupropion 255 and 164. Furhtermore, reboxetine, citalopram and the selective DA reuptake inhibitor GBR12909 infused locally in the BNST, through the dialysis fiber increase in a different manner catecholamine release in the BNST. These results suggest that catecholamine transmission in the BNST might be a common downstream pathway that is involved in the mechanism of action of antidepressants and consequently it can be hypothesized that a dysfunction of neuronal transmission in this brain area might have a role in the aetiology of affective disorders. On these bases it can be also suggested that modulation of catecholamine transmission in the BNST can be utilized in the screening process of new antidepressant

    Ketamine modulates catecholamine transmission in the bed nucleus of stria terminalis: The possible role of this region in the antidepressant effects of ketamine

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    Since the therapeutic treatment of depression is far from being satisfactory, new therapeutic strategies ought to be pursued. In addition, further investigation on brain areas involved in the action mechanism of antidepressants can shed light on the aetiology of depression. We have previously reported that typical and atypical antidepressants strongly stimulate catecholamine transmission in the bed nucleus of stria terminalis (BNST). In this study, we have built on that work to examine the effect of ketamine, an unusual antidepressant that can produce a fast-acting and long-lasting antidepressant effect after administration of a single sub-anaesthetic dose. Ketamine is an antagonist of the ionotropic N-methyl-D-aspartate (NMDA) receptor but can also act through its metabolite (2R-6R)-hydroxynorketamine. Using the microdialysis technique in freely moving rats, we monitored the acute effect of ketamine on catecholamine release in the BNST to gain clues to its prompt antidepressant effect. Male Sprague-Dawley rats were implanted with a microdialysis probe in the BNST and 48 h later, were injected with ketamine (10, 20, and 40 mg/kg, i.p.). Ketamine increased norepinephrine (127%, 155%, 186%) and dopamine (114%, 156%, 176%) extracellular concentration above basal in a time and dose dependent manner, without significantly modifying motility. Since the effect of ketamine, although lower, was not substantially different from that produced by classical antidepressants, we suggest that catecholamine increase in BNST is not likely to be related to a rapid ketamine antidepressant effect, though it might be related to its performance in predictive tests of antidepressant properties

    Different classes of antidepressants increase dopamine and norepinephrine release in the bed nucleus of stria terminalis: an “in vivo” microdialysis study

    No full text
    Antidepressants include a relatively wide spectrum of drugs that increase the synaptic concentration of monoamines, mostly through neurotransmitter reuptake blockade. The bed nucleus of stria teminalis (BNST) is an area that is considered part of the extended amygdala, a complex involved in the acquisition and expression of emotions. BNST, is richly innervated by monoamines, sends projections back to monoamine neurons and is considered a relay station in mediating the activation stress response. Since the systemic administration of reboxetine, a selective norepinephrine transporter (NET) blocker increases the extracellular concentration (output) of norepinephrine (NE) but also of dopamine (DA) in the BNST, it is conceivable that catecholamine transmission in BNST could be involved in the mechanism of action of antidepressants The aim of this study was to characterize the acute effect of antidepressants belonging either to the NET blockers category or to the 5-HT reuptake blockers category (SSRI) on DA and NE ouput in the BNST, assayed through the in vivo microdialysis technique. The results obtained show that all the tested antidepressants (5 to 20 mg/kg i.p.) increased, dose dependently, NE and DA in the BNST. In particular, the increase reported for NE and DA respectively in % over basal were were as follows: desipramine, 239 and 137; reboxetine 185 and 128; imipramine 512 and 359; citalopram 95 and 122; fluoxetine 122 and 68; bupropion 255 and 164. These results suggest that catecholamine transmission in the BNST might be a common downstream pathway that is involved in the mechanism of action of antidepressants and consequently it can be hypothesized that a dysfunction of neuronal transmission in this brain area might have a role in the aetiology of affective disorders

    Long term effects of adolescent chronic mild stress on brain catecholamine transmission in rat brain: a microdialysis study

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    Aims: Although the aetiology of depression is largely unknown, it is widely accepted that epigenetic factors such as chronic stress may have a prominent role in the manifestation of this illness. We previously observed that young adult rats born from dams exposed to restrain stress in the last week of pregnancy had basal and stimulated catecholamine transmission alteration in the nucleus accumbens (NAcc) (Silvagni A. 2008). We intended to study the alteration of catecholamine transmission in the NAcc shell of adult rats exposed to unpredictable chronic stress (UCMS) at adolescent age to shed light on depression aetiology. Methods: By means of microdialysis we studied basal and stimulated dopamine and noradrenaline release in the NAcc shell of adult rats that were exposed UPS at peri-adolescent age (28-42 PND). Results: We observed that UPS determined i) an increased basal level of dopamine but not noradrenaline in the NAcc.; ii) a reduced response to amphetamine (0.5 mg/kg ip) of both dopamine and noradrenaline release; iii) an increased response to the dopamine reuptake blocker GBR 12909 (10 mg/kg ip) to dopamine but not noradrenaline release. Conclusions: These results suggest that catecholamine transmission in the Nacc shell is involved long term effect of UCMS. In particular we can hypothesize that dopamine basal release and reuptake may be correlated with vesicular dopamine content and mobilization and a dysfunction of this process may be linked to anhedonia and in turn involved in the aetiology of depression

    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

    Role of prefrontal cortex dopamine and noradrenaline circuitry in addiction

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    Understanding the mechanisms of drug dependence has been the goal of a large number of neuroscientists, pharmacologists and clinicians who carried out research with the hope of individuating and proposing an efficacious therapy for this disorder (Sofuoglu, 2010; Kalivas and Volkow, 2011). Unfortunately, although huge efforts, drug dependence is still a relevant health, social and economical problem (Popova et al., 2012; Hiscock et al., 2011; Shorter and Kosten, 2011). Treatments for drug abuse are for the most part ineffective because the molecular and cellular mechanisms through which drugs of abuse alter neuronal circuitry are still unexplained and above all, because drugs of abuse determine a global alteration of cerebral functions that govern behaviour through decision formation, making therefore unfocused the identification of a pharmacological target (Volkow et al., 2011; Schultz 2011). One of the first strategies pursued in drug dependence therapy was directed to removal of pleasure associated with drug taking, but the compliance with the treatment has been always limited, although it could improve when it was supported by psychology based motivational therapy as in alcohol dependence (Krampe and Ehrenreich, 2010; Simkin and Grenoble, 2010). On the other hand it is not infrequent that heavy smokers or heavy drinkers stop suddenly dependence just because their will overcome year-long habits. Decision making is a process based on the interaction between prefrontal cortex (PFC) and subcortical regions involved in reward and motivation, therefore it is likely that failure in self-regulatory behavior, that is common in addicted subjects, could be dependent upon the alteration of interactions between the prefrontal cortex and subcortical regions (Heatherton and Wagner, 2011). In this chapter we will review the role of PFC in addiction with particular attention to dopamine and norepinephrine transmission

    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

    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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