1,720,961 research outputs found
Anxiolytic properties of endogenously occurring pregnanediols in two rodent models of anxiety
No full textCertain endogenously occurring 3 alpha-hydroxylated, 5-reduced pregnane steroids act at a specific site on the GABA(A) receptor complex (GRC) to modulate the effects of GABA at its receptor. Modulators that potentiate GABA at the GABA(A) receptor often possess anxiolytic properties. The anxiolytic potential of four 5-reduced, 3 alpha, 20-pregnanediols, differing only in the stereochemical orientation of the steroid A-ring and the 20-hydroxyl group, were tested in the Vogel test following intracerebroventricular (ICV) administration. The effects of these pregnanediols were compared to those of their 20-ketone analogues, 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 beta-P) and 3 alpha-hydroxy-5 beta-pregnan-20-one (3 alpha,5 beta-P). All four pregnanediols tested significantly enhanced punished drinking at doses ranging from 10 to 60 mu g. The rank order of potency based on the minimum effective dose (MED) observed was 5 alpha-pregnan-3 alpha,20 alpha-diol = 5 beta-pregnan-3 alpha,20 alpha-diol > 5 beta-pregnan-3 alpha,20 beta-diol > 5 alpha-pregnan-3 alpha,20 beta-diol. 3 alpha,5 beta-P and 3 alpha,5 alpha-P enhanced punished responding when administered at 2.5 and 5 mu g, respectively. 3 beta,5 alpha-P which is inactive at the GRC was also inactive (up to 100 mu g) in the Vogel test. The benzodiazepine control diazepam was efficacious when administered at 2.5 mu g. 5 alpha-Pregnan-3 alpha,20 alpha-diol was further tested in the mouse elevated plus-maze model following systemic administration where it was found to be active in a dose range of 10-40 mg/kg IP. These results raise the possibility that in addition to 3 alpha,5 alpha-P and 3 alpha,5 beta-P, some of their endogenously occurring pregnanediol metabolites may also influence physiological processes related to anxiety via the GRC
Characterization of peripheral benzodiazepine type sites in a cultured murine BV-2 microglial cell line
No full textIt is known that the density of peripheral benzodiazepine receptors (PBR) increases after brain damage. Astrocytes are among the cell types where PBR ligand binding has been detected and may be involved in the response to neuronal injury and regeneration. Consistent with the hypothesis, the apparent density of PER sites in astrocytes is increased by both cytokines and neurotoxins. However, microglia, the resident macrophages which represent 5-15% of glial cell populations have not been evaluated for the presence of the PER. In the present study, we report the presence of [H-3]Ro5-4864 binding in microglial cells. In particular, we used BV-2 cells, an immortalized cell line of murine microglial cells. High affinity binding of [H-3]Ro5-4864 to a single site was detected in membranes prepared from BV-2 cells (K-D = 4.4 nM, B-max = 3,800 fmoles/mg protein). Various ligands for the PER displaced [H-3]Ro5-4864 binding with the following rank order of potencies: PK11195 = Ro5-4864 > FGIN-1-27 > triazolam = diazepam > beta-pro-pyl-beta-carboline-3-carboxylate = clonazepam > lorazepam = flurazepam >> chloridazepoxide = clorazepate. Subcellular fractionationstudies indicate that the majority of the Ro5-4864 binding sites is in the mitochondrial fraction. The remainder is found in nonmitochondrial cell fractions. The [H-3]Ro5-4864 binding observed on intact cells had characteristics similar to those found on membranes. The presence of a high density of PBRs in these cells establish the basis for additional investigations into their possible functional role, if any, in the microglial response to neuronal injury. (C) 1996 Wiley-Liss, Inc
The positive allosteric modulator of nicotinic alpha 7 cholinergic receptor, AVL-3288, stimulates cathecolamine release in the prefrontal cortex and nucleus accumbens shell of adolescent rats: potential utility in ADHD?
No full textThe alpha 7 nicotinic acetylcholine receptor (nAChR) allosteric modulator UCI-40083 differentially increases dopamine (DA) and norepinephrine (NE) release in adolescent rat brain
No full textThe selective α7 nAChR positive allosteric modulator UCI-40083 (N-(4-chlorophenyl)-α-[[(4-chlorophenyl)amino]methylene]-3-methyl-5-isoxazolacet-amide), has been shown to evoke robust positive modulation of agonist-induced currents at α7 nAChRs. In order to evaluate its pharmacological potential in cognition disorders such as the attention deficit with hyperactivity disorder (ADHD), we assessed the effect of systemic UCI-40083 administration on DA and NE release in the medial prefrontal cortex (PFC) of adolescent spontaneous hypertensive (SHR) and Sprague Dawley (SD) rats, by using a microdialysis technique in freely moving animals. We also assessed the effect on DA and NE release in the nucleus accumbens (NAcc) shell to gain insight into potential motivational properties of UCI-40083. Our results show that UCI-40083 (1 mg/kg i.p.) increases NE and DA in the PFC of both SD and SHR rats. This effect yielded an optimum dose as the effect of 3 mg/kg was not significantly different (NE) or was lower (DA) when compared to 1 mg/kg in both strains. In addition, our results show that UCI-40083 significantly increased DA and NE output in the NAcc shell of both SD and SHR rats. The stimulant effect on DA and NE levels in the PFC was blocked by the selective α7 nAChR antagonist methyllycaconitine (MLA) at 3 mg/kg i.p. In summary our results suggest that UCI-40083 has the potential of modulating catecholamine transmission in the PFC and in the NAcc shell and thus may possess cognitive and motivational properties, features that are shown also by stimulant drugs currently used in ADHD therapy such as amphetamine and methylphenidate. (NIH grant MH080246
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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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