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Baltimore & Ohio (B & O) 7142
No full textA photograph postcard showing theBaltimore & Ohio (B & O) 7142, 2-8-8-0, at M & K Junction, W.VA
The anxiogenic drug FG-7142 increases serotonin metabolism in the rat medial prefrontal cortex
No full textThe neural mechanisms underlying anxiety states are believed to involve interactions among forebrain limbic circuits and brainstem serotonergic systems. Consistent with this hypothesis, FG-7142, a partial inverse agonist at the benzodiazepine allosteric site of the GABAA receptor, increases c-Fos expression within a subpopulation of brainstem serotonergic neurons. Paradoxically, FG-7142 has no effect on extracellular serotonin concentrations, as measured using in vivo microdialysis, in certain anxiety-related brain structures. This study tested the hypothesis that FG-7142 alters serotonin metabolism within one or more nodes of a defined anxiety-related forebrain circuit. Rats received one of four treatments (vehicle, 1.9, 3.8, or 7.5 mg/kg FG-7142, i.p.) and brains were collected 1 h following treatment. Thirteen forebrain regions were microdissected and analyzed for l-tryptophan, serotonin, and 5-hydroxyindoleacetic acid concentrations using high pressure liquid chromatography with electrochemical detection. FG-7142 (7.5 mg/kg) increased l-tryptophan, serotonin, and 5-hydroxyindoleacetic acid concentrations in the prelimbic cortex but not in several other regions studied including subdivisions of the amygdala and bed nucleus of the stria terminalis. These data demonstrate that FG-7142 alters brain tryptophan concentrations and serotonin metabolism in specific components of an anxiety-related forebrain circuit including the medial prefrontal cortex, an important structure involved in executive function and the regulation of emotional behavior.The neural mechanisms underlying anxiety states are believed to involve interactions among forebrain limbic circuits and brainstem serotonergic systems. Consistent with this hypothesis, FG-7142, a partial inverse agonist at the benzodiazepine allosteric site of the GABAA receptor, increases c-Fos expression within a subpopulation of brainstem serotonergic neurons. Paradoxically, FG-7142 has no effect on extracellular serotonin concentrations, as measured using in vivo microdialysis, in certain anxiety-related brain structures. This study tested the hypothesis that FG-7142 alters serotonin metabolism within one or more nodes of a defined anxiety-related forebrain circuit. Rats received one of four treatments (vehicle, 1.9, 3.8, or 7.5 mg/kg FG-7142, i.p.) and brains were collected 1 h following treatment. Thirteen forebrain regions were microdissected and analyzed for l-tryptophan, serotonin, and 5-hydroxyindoleacetic acid concentrations using high pressure liquid chromatography with electrochemical detection. FG-7142 (7.5 mg/kg) increased l-tryptophan, serotonin, and 5-hydroxyindoleacetic acid concentrations in the prelimbic cortex but not in several other regions studied including subdivisions of the amygdala and bed nucleus of the stria terminalis. These data demonstrate that FG-7142 alters brain tryptophan concentrations and serotonin metabolism in specific components of an anxiety-related forebrain circuit including the medial prefrontal cortex, an important structure involved in executive function and the regulation of emotional behavior
Systemic administration of the benzodiazepine receptor partial inverse agonist FG-7142 disrupts corticolimbic network interactions
No full textThe medial prefrontal cortex (mPFC) and basolateral amygdala(BLA) coordinate various stress responses. Although the effects of stressors on mPFCand BLA activity have been previously examined, it remains unclear to what extent stressors affect functional interactions between these regions. In vivo electrophysiology in the anesthetized rat was used to examine mPFC and BLA activity simultaneously in response to FG-7142, a benzodiazepine receptor partial inverse agonist that mimics various stress responses, in an attempt to model the effects of stressors on corticolim-bic functional connectivity. Extracellular unit and local field potential (LFP) recordings, using multielectrode arrays positioned in mPFC and BLA, were conducted underbasal conditions and in response to systemic FG-7142 administration. This drug increased mPFC and BLA unit firing at the lowest dose tested, whereas higher doses of FG-7142 decreased various burst firing parameters in both regions. Moreover, LFP power was attenuated at lower (<1 Hz) and potentiated at higher frequencies in mPFC (1–12 Hz) and BLA (4–8 Hz). Interestingly, FG-7142 diminished synchronized unit firing, both within and between mPFC and BLA. Finally, FG-7142 decreased LFP synchronization between these regions. In a separate group of animals, pretreatment with the selective benzodiazepine receptor antagonist flumazenil blocked the changes in burst firing, LFP power and synchronized activity induced by FG-7142, confirming direct benzodiazepine receptor-mediated effects. These results indicate that FG-7142 disrupts corticolimbic network interactions via benzodiazepine receptor partial inverse agonism. Perturbation of mPFC-BLA functional connectivity induced by FG-7142 may provide a useful model of corticolimbic dysfunction induced by stressors
β-Carboline (FG-7142) modulates fear but not anxiety-like behaviour in zebrafish
No full textAbstract The β-Carboline FG-7142 is a partial inverse agonist at the benzodiazepine allosteric site on the GABA-A receptor that induces anxiogenic, proconvulsant, and appetite-reducing effects in many species, including humans. Seizure-kindling effects have been well studied, however anxiogenic properties are relatively unexplored. This study aimed to investigate concentration-dependent effects of FG-7142 on anxiety-like behaviour and fear responses in zebrafish (Danio rerio) using the open-field test (OF) and novel object approach test (NOA). A U-shaped distribution was found with maximal responses in increased immobility and reduced distance moved at 10 µM in the NOA but not the OF. Follow up experiments demonstrated a lack of effect in repeated OF testing and no changes in opercular movements. Furthermore, the effect of FG-7142 was reversed with ethanol treatment. These results suggest that FG-7142 elicits a ‘freezing’ response in zebrafish via the introduction of novelty, suggesting fear-induction. These findings indicate that FG-7142 may act as an agent to promote acute fear responses in zebrafish
Investigating the Anxiety-Increasing Potential of β-Carboline (FG-7142) in Zebrafish
No full textβ-Carboline (FG-7142) is a partial inverse agonist of the benzodiazepine allosteric site at the GABA-A receptor. It has been shown to yield anxiety-increasing (anxiogenic), proconvulsant, and appetite-reducing effects among various aquatic and mammalian species, including humans. It is found naturally in succulents, hallucinogenic plants, as well as tobacco leaves, and may be made endogenously. While previous literature has focused on seizure-inducing effects, interest is growing in the anxiogenic effects it has on terrestrial and aquatic species to model high-anxiety states. This study aimed to (1) establish a dose response curve for anxiety-like behaviour in zebrafish and (2) evaluate FG-7142 in a conditioned fear paradigm. An open field test and novel object approach test were used to generate a dose response curve of FG-7142 on anxiety-like behaviours. A U-shaped distribution curve was found with peak responses in increased immobility, lowered velocity, and lowered distance travelled at 10.0 μM. These findings suggest that FG-7142 has a significant effect on some behavioural markers of increased anxiety. Currently, this effective dose of 10.0 μM is being used to evaluate fear and anxiety conditioning in zebrafish using a 3-day repeated exposure and subsequent submerged plus maze paradigm based on red-green colour preference. Should FG-7142 have a mediating effect in the formation of conditioned fear and anxiety responses, it is expected that zebrafish in this test should avoid locations in the plus maze associated with the colour that was present during their respective repeated exposures.
Faculty Mentor: Dr. Trevor Hamilton 
<i>miR-7142</i> seed binding interrogation on the 3’ UTR of DEGs.
No full textmiR-7142 seed binding interrogation on the 3’ UTR of DEGs.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
FG 7142 specifically reduces meal size and the rate and regularity of sustained feeding in female rats: Evidence that benzodiazepine inverse agonists reduce food palatability
No full textBenzodiazepine receptor inverse agonists reduce food intake in males, but their actions in females, in whom stress-related eating disorders are more common, as well as their behavioral mode of action remain unclear. The consummatory effects of benzodiazepine receptor ligands have alternately been hypothesized to reflect changes in the hedonic evaluation of food or secondary effects of anxiety-related or cognitive properties. To test the anorectic mode of action of benzodiazepine inverse agonists, the effects of FG 7142 on feeding microstructure were studied in nondeprived female Wistar rats (n=32). Microstructure analysis used a novel meal definition that recognizes prandial drinking. On pharmacologically synchronized diestrus I, rats were pretreated (-30 min dark onset) with the benzodiazepine partial inverse agonist FG 7142 (i.p. 0, 3.75, 7.5, 15 mg/kg) in a between-subjects design. FG 7142 delayed the onset of (16-541%), decreased the amount eaten (36-52%) and drunk (63-87%), and reduced the time spent drinking (59-87%) within the first nocturnal meal. Dose-dependent incremental anorexia continued 6 h into the dark cycle, whereas FG 7142 did not suppress the quantity, duration or rate of drinking past the first meal. Treated rats ate smaller meals (17-42%) of normal duration. This reflected that FG 7142 slowed feeding within meals (9-38%) by decreasing the regularity and maintenance of feeding from pellet-to-pellet. FG 7142 did not influence postprandial satiety; meal frequency and inter-meal intervals were unaffected. FG 7142 anorexia was blocked by the benzodiazepine receptor antagonist flumazenil in a 2:1 molar ratio (n=17 rats). The very early, nonspecific (+10 min), but not subsequent (2.5, 4.5 h) feeding-specific phase, of FG 7142 anorexia was mirrored by anxiogenic-like behavior in FG 7142-treated (7.5 mg/kg) female rats (n=48) in the elevated plus-maze. Thus, benzodiazepine receptor inverse agonists preferentially lessen the maintenance of feeding in female rats, effects opposite to those of palatable food. © 2007 Nature Publishing Group All rights reserved
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