Effects of Acute and Chronic Treatment of Novel Psychotropic Drug, 8- (Trifluoromethyl)-1, 2, 3, 4, 5-benzopentathiepin-6-amine Hydrochloride (TC-2153), on the Behavior of Zebrafish (Danio Rerio): A Comparison with Fluoxetine

2019 ◽  
Vol 16 (12) ◽  
pp. 1321-1328
Author(s):  
Alexander Kulikov ◽  
Nadezhda Sinyakova ◽  
Elizabeth Kulikova ◽  
Tatyana Khomenko ◽  
Nariman Salakhutdinov ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Chronic Treatment ◽  
Tyrosine Phosphatase ◽  
Anxiolytic Effect ◽  
Chronic Administration ◽  
Positive Control ◽  
Amine Hydrochloride ◽  
Suitable Model ◽  
L 14 ◽  
New Generation

Background: Striatal-enriched Tyrosine Phosphatase (STEP) plays a key role in the mechanisms of neuronal signaling and is a potential molecular target for new generation of psychotropic drugs. STEP inhibitor, 8-(trifluoromethyl-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153), shows anxiolytic effect on mice. Zebrafish (Danio rerio) is a suitable model for the study of anxiety pharmacology. Objective: The objective of this study is to investigate the effects of acute and chronic TC-2153 treatment on zebrafish anxiety-related behavior. Methods: The effects of acute (0.125 and 0.25 mg/l, 3 h) and chronic (0.125 mg/l, 14 days) administration of TC-2153 on locomotion and anxiety-related behavior (time spent near the bottom and mean distance from the bottom) of adult zebrafish in the Novel Tank (NT) test were compared with those of the same doses of fluoxetine chosen as a positive control. Results: Acute treatment with 0.125 mg/l and 0.25 mg/l of TC-2153 or fluoxetine decreased time spent near the bottom, increased time spent near the surface and increased mean distance from the bottom of tank. Chronic treatment with 0.125 mg/l of TC-2153 reduced only time spent near the tank bottom without any effect on time spent near the surface and mean distance from the bottom, while chronic administration of 0.125 mg/l of fluoxetine altered these three indices of anxiety. Conclusion: Both acute and chronic TC-2153 produces anxiety-like effect indicating STEP involved in the mechanism of anxiety-related behavior in zebrafish. At the same time, chronic treatment with TC-2153 reduced locomotor activity. Zebrafish is a promising laboratory object to study the role of STEP in the nervous system.

scholarly journals Absence of sibutramine effect on spontaneous anxiety in rats

2010 ◽  
Vol 54 (4) ◽  
pp. 375-380 ◽  
Author(s):  
Silvana S. Frassetto ◽  
Isis O. Alves ◽  
Marislane M. Santos ◽  
Ana E. S. Schmidt ◽  
Janaína J. Lopes ◽  
...  
Keyword(s):  
Chronic Treatment ◽  
Elevated Plus Maze ◽  
Anxiolytic Effect ◽  
Chronic Administration ◽  
Positive Control ◽  
Maximum Effect ◽  
Plus Maze ◽  
The Central Nervous System ◽  
Treatment Of Obesity ◽  
Acute And Chronic Treatments

INTRODUSTION: Sibutramine has been described as a drug recommended for treatment of obesity, since it has the ability to inhibit the reuptake of serotonin and noradrenaline in the central nervous system, thereby increasing energy expenditure. OBJECTIVE: Investigate the anxiogenic and anxiolytic effects of acute and chronic treatment with sibutramine in rats submitted to the task of the elevated plus-maze. METHODS: Diazepam was used as a positive control for the anxiolytic effect, and the task of the elevated plus-maze showed sensitivity to detect the effect. In the chronic treatment, sibutramine was ingested for a period of two months. RESULTS: The acute and chronic treatments at the studied dose, which is described to produce a maximum effect of anti-obesity in rats, did not interfere with anxiety. CONCLUSIONS: The acute and chronic administration of sibutramine is not related to anxiolytic or anxiogenic effects.

Inhibition of Protein Tyrosine Phosphatase 1B by Lutein Derivatives isolated from Mexican Oregano (Lippia graveolens)

2018 ◽  
Vol 17 (3) ◽  
pp. 134-139
Author(s):  
R.M. Perez-Gutierrez
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Spectroscopic Data ◽  
Methanol Extract ◽  
Tyrosine Phosphatase ◽  
Positive Control ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ic50 Value ◽  
Ic50 Values

Methanol extract from Lippia graveolens (Mexican oregano) was studied in order to identify inhibitory bioactives for protein tyrosine phosphatase 1B (PTP1B). Known flavone as lutein (1), and another flavone glycoside such as lutein-7-o-glucoside (2), 6-hydroxy-lutein-7-ohexoside (3) and lutein-7-o-ramnoide (4) were isolated from methanol extract of aerial parts of the Lippia graveolens. All isolates were identified based on extensive spectroscopic data analysis, including UV, IR, NMR, MS and compared with spectroscopic data previously reported. These flavones were evaluated for PTP1B inhibitory activity. Among them, compounds 1 and 3 displayed potential inhibitory activity against PTP1B with IC50 values of 7.01 ± 1.25 μg/ml and 18.4 μg/ml, respectively. In addition, compound 2 and 4 showed moderate inhibitory activity with an IC50 value of 23.8 ± 6.21 and 67.8 ± 5.80 μg/ml respectively. Among the four compounds, luteolin was found to be the most potent PTP1B inhibitor compared to the positive control ursolic acid, with an IC50 value of 8.12 ± 1.06 μg/ml. These results indicate that flavonoids constituents contained in Lippia graveolens can be considered as a natural source for the treatment of type 2 diabetes.

scholarly journals Inhibitory Effects of Secondary Metabolites from the Lichen Stereocaulon evolutum on Protein Tyrosine Phosphatase 1B

Planta Medica ◽  
2021 ◽  
Author(s):  
Birgit Waltenberger ◽  
Françoise Lohézic-Le Dévéhat ◽  
Thi Huyen Vu ◽  
Olivier Delalande ◽  
Claudia Lalli ◽  
...  
Keyword(s):  
Protein Tyrosine Phosphatase ◽  
Inhibitory Activity ◽  
Tyrosine Phosphatase ◽  
Inhibitory Effect ◽  
Positive Control ◽  
Protein Tyrosine Phosphatase 1B ◽  
Protein Tyrosine ◽  
Ic50 Values ◽  
A Cell

AbstractProtein tyrosine phosphatase 1B plays a significant role in type 2 diabetes mellitus and other diseases and is therefore considered a new drug target. Within this study, an acetone extract from the lichen Stereocaulon evolutum was identified to possess strong protein tyrosine phosphatase 1B inhibition in a cell-free assay (IC50 of 11.8 µg/mL). Fractionation of this bioactive extract led to the isolation of seven known molecules belonging to the depsidones and the related diphenylethers and one new natural product, i.e., 3-butyl-3,7-dihydroxy-5-methoxy-1(3H)-isobenzofurane. The isolated compounds were evaluated for their inhibition of protein tyrosine phosphatase 1B. Two depsidones, lobaric acid and norlobaric acid, and the diphenylether anhydrosakisacaulon A potently inhibited protein tyrosine phosphatase 1B with IC50 values of 12.9, 15.1, and 16.1 µM, respectively, which is in the range of the protein tyrosine phosphatase 1B inhibitory activity of the positive control ursolic acid (IC50 of 14.4 µM). Molecular simulations performed on the eight compounds showed that i) a contact between the molecule and the four main regions of the protein is required for inhibitory activity, ii) the relative rigidity of the depsidones lobaric acid and norlobaric acid and the reactivity related to hydrogen bond donors or acceptors, which interact with protein tyrosine phosphatase 1B key amino acids, are involved in the bioactivity on protein tyrosine phosphatase 1B, iii) the cycle opening observed for diphenylethers decreased the inhibition, except for anhydrosakisacaulon A where its double bond on C-8 offsets this loss of activity, iv) the function present at C-8 is a determinant for the inhibitory effect on protein tyrosine phosphatase 1B, and v) the more hydrogen bonds with Arg221 there are, the more anchorage is favored.

Effects of acute and chronic treatment of STEP inhibitor, TC-2153, on the nervous system and behaviour of zebrafish (Danio rerio)

2019 ◽  
Vol 29 ◽  
pp. S198-S199
Author(s):  
A. Kulikov ◽  
N. Sinyakova ◽  
E. Kulikova ◽  
N. Evglevsky ◽  
I. Kolotygin ◽  
...  
Keyword(s):  
Nervous System ◽  
Danio Rerio ◽  
Chronic Treatment ◽  
Acute And Chronic Treatment

Effect of tianeptine on neuroendocrine, enzyme and behavioral responses to restraint stress in male rats

1993 ◽  
Vol 8 (S2) ◽  
pp. 67s-73s ◽  
Author(s):  
R Fontanges ◽  
J Mimouni ◽  
X de Grieve ◽  
J Picard ◽  
M Pugeat ◽  
...  
Keyword(s):  
Open Field ◽  
Restraint Stress ◽  
Wistar Rats ◽  
Chronic Treatment ◽  
Single Injection ◽  
Behavioral Responses ◽  
Chronic Administration ◽  
Exploratory Activity ◽  
Male Rats ◽  
The Novel

SummaryThe effects of the novel antidepressant tianeptine, after acute or chronic administration, were compared in normal and restraint-stressed (30 min or 2 h) Wistar rats. Tianeptine, at the dose of 10 mg/kg, did not exert any effect in non-stressed rats. However, in animals restrained for 30 min, tianeptine reduced the increase of circulating ACTH and β-endorphin levels without modification of corticosterone. Moreover, it antagonized the deficit of vertical exploratory activity in an open field. In rats restrained for 2 hours, a single injection of tianeptine suppressed the stress-induced increase of TAT hepatic activity and moderately attenuated the deficit of activity in the open field. This effect was less marked and not statistically significant after chronic treatment.

Oxcarbazepine does not suppress cortical spreading depression

Cephalalgia ◽  
2010 ◽  
Vol 31 (5) ◽  
pp. 537-542 ◽  
Author(s):  
Ulrike Hoffmann ◽  
Ergin Dileköz ◽  
Chiho Kudo ◽  
Cenk Ayata
Keyword(s):  
Single Dose ◽  
Cortical Spreading Depression ◽  
Chronic Treatment ◽  
Spreading Depression ◽  
Screening Tool ◽  
Positive Control ◽  
Migraine Prophylaxis ◽  
Migraine Aura ◽  
Predictive Utility ◽  
Prophylactic Drugs

Background: Cortical spreading depression is the electrophysiological substrate of migraine aura, and may trigger headache. Recently, chronic treatment with five migraine prophylactic drugs was shown to suppress cortical spreading depression, implicating spreading depression as a common therapeutic target in migraine prophylaxis. Materials and methods: In order to assess the negative predictive value of spreading depression susceptibility as a preclinical drug screening tool, we tested oxcarbazepine, an anti-epileptic ineffective in migraine prophylaxis. Valproate served as the positive control. Cortical spreading depression susceptibility was measured in rats using topical KCl or electrical stimulation. Results: Oxcarbazepine did not suppress spreading depression either after a single dose or after daily treatment for 5 weeks. As previously shown, valproate suppressed spreading depression susceptibility after chronic dosing, while a single dose was ineffective. Conclusions: These data provide further support for spreading depression as a relevant target in migraine prophylaxis, and demonstrate the predictive utility of employed spreading depression models.

Effect of Isomers of DDD on thyroid and adrenal function in rats

1968 ◽  
Vol 46 (1) ◽  
pp. 59-66 ◽  
Author(s):  
M. J. Fregly ◽  
I. W. Waters ◽  
J. A. Straw
Keyword(s):  
Body Weight ◽  
Thyroid Gland ◽  
Chronic Treatment ◽  
Chronic Administration ◽  
Hepatic Metabolism ◽  
Control Group ◽  
Albino Rats ◽  
Specific Effects ◽  
Rate Of Oxygen Consumption

Dietary administration of o,p′-DDD (2,2-bis(2-chlorophenyl, 4-chlorophenyl)-1,1-dichloroethane) at 1.0 and 3.0 g/kg food for 6 weeks increased the thyroid weight of male albino rats by 62 and 81% respectively. The rate of oxygen consumption (measured at 30 °C) and gain in body weight were unaffected by treatment. The rate of loss of 131I from the thyroid gland was significantly faster for both treated groups than for controls. These results suggest that the chronic administration of o,p′-DDD at the doses used resulted in a compensated hypothyroidism in rats. In another experiment, the thyroid weight of female hooded rats given m,p′-DDD (1.0 g/kg food) and p,p′-DDD (1.0 and 3.0 g/kg food) for 24 weeks also increased 112, 94, and 113% respectively above control weight. Ninety-six hours after the administration of thyroxine-131I, significantly greater fecal and less urinary excretion of radioactivity was observed for all treated groups than for the control group. The increase in thyroid weight of the treated rats may be associated with increased hepatic metabolism of thyroxine, but specific effects on the thyroid gland have not been excluded. Although isomers of DDD are reported to induce atrophy of the adrenal cortex and to reduce glucocorticoid secretion in dogs, no effect of the chronic administration of isomers of DDD on adrenal weight or production of either total Δ4-3 ketosteroids or corticosterone in vitro was observed in the case of rats. The rate of metabolism of desoxycorticosterone in vitro by rat liver slices was also unaffected by chronic treatment with o,p′-DDD.

scholarly journals mGluR5 Negative Modulators for Fragile X: Resistance and Persistence

2021 ◽  
Author(s):  
David C. Stoppel ◽  
Patrick K. McCamphill ◽  
Rebecca K. Senter ◽  
Arnold J. Heynen ◽  
Mark F. Bear
Keyword(s):  
Clinical Trials ◽  
Protein Synthesis ◽  
Chronic Treatment ◽  
Metabotropic Glutamate Receptor ◽  
Glycogen Synthase ◽  
Fragile X ◽  
Treatment Resistance ◽  
Chronic Administration ◽  
Inhibitory Avoidance ◽  
Cross Tolerance

Fragile X syndrome (FXS) is caused by silencing of the human FMR1 gene and is the leading monogenic cause of intellectual disability and autism. Abundant preclinical data indicated that negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGluR5) might be efficacious in treating FXS in humans. Initial attempts to translate these findings in clinical trials have failed, but these failures provide the opportunity for new discoveries that will improve future trials. The emergence of acquired treatment resistance (tolerance) after chronic administration of mGluR5 NAMs is a potential factor in the lack of success. Here we confirm that FXS model mice display acquired treatment resistance after chronic treatment with the mGluR5 NAM CTEP in three assays commonly examined in the mouse model of FXS: (1) audiogenic seizure susceptibility, (2) sensory cortex hyperexcitability, and (3) hippocampal protein synthesis. Cross-tolerance experiments suggest that the mechanism of treatment resistance likely occurs at signaling nodes downstream of glycogen synthase kinase 3α (GSK3α), but upstream of protein synthesis. The rapid emergence of tolerance to CTEP begs the question of how previous studies showed an improvement in inhibitory avoidance (IA) cognitive performance after chronic treatment. We show here that this observation was likely explained by timely inhibition of mGluR5 during a critical period, as brief CTEP treatment in juvenile mice is sufficient to provide a persistent improvement of IA behavior measured many weeks later. These data will be important to consider when designing future fragile X clinical trials using compounds that target the mGluR5-to-protein synthesis signaling cascade.

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