scholarly journals Assessment of dose-dependent effects of anxiolytics of benzodiazepine structure with diazepam as an example in Danio Rerio

2020 ◽  
Vol 18 (1) ◽  
pp. 43-49
Author(s):  
Aleksandr S. Devyashin ◽  
Aleksandra A. Blazhenko ◽  
Viktor A. Lebedev ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Stress Test ◽  
Dose Range ◽  
Control Group ◽  
The Novel ◽  
Gaba A ◽  
Small Doses ◽  
Pharmacological Substance ◽  
Dose Dependent ◽  
Dose Dependent Effect

Abstract. The effect of benzodiazepine anxiolytic diazepam in Danio rerio was investigated. Methods. A stress test on novelty situation was used: a fish was placed first in a beaker with a dissolved pharmacological substance (or water) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of freezing of the experiment were measured. Results. In response to the novelty of tank, the fish was shown to react by submerging to the bottom, increasing the freezing, and reducing the number of movements to the upper half of the novel tank. After diazepam exposure (administration), the fish was not only in the lower, but also in the upper part of the novel tank. A pharmacological analysis of diazepam effect in Danio rerio showed that in a certain dose range of 110 mg/l anxiolytic reduces (in comparison with the control group of fish) the number and time of freezing, increases the number of movements in the upper half of the tank and the swimming time in upper part of the tank. Diazepam causes a disinhibition of motor activity at doses of 1 and 5 mg/l, which may be explained by the effect of small doses of tranquilizers on presynaptic GABA-A autoreceptors. Diazepam 20 mg/l has a depriving effect. Conclusion. Diazepam acts in a higher dose range (110 mg/l) than phenazepam (0.11 mg/l) in Danio rerio. At the same time, diazepam is characterized by a domed dose-dependent effect, in contrast to the action of phenazepam. The prospect of using Danio rerio as an animal model in behavioral pharmacology is not inferior to studies in rodents.

Behavioral analysis of anxiolytic action of phenazepam in conditions of an acute psychogenic stress (predator presentation) in Danio rerio

2021 ◽  
Vol 19 (1) ◽  
pp. 71-78
Author(s):  
Andrei A. Lebedev ◽  
Aleksandr S. Devyashin ◽  
Aleksandra A. Blazhenko ◽  
Sergei V. Kazakov ◽  
Viktor A. Lebedev ◽  
...  
Keyword(s):  
Danio Rerio ◽  
Path Length ◽  
Stress Test ◽  
Control Group ◽  
The Novel ◽  
Highly Sensitive ◽  
Psychogenic Stress ◽  
Pharmacological Substance ◽  
Dose Dependent ◽  
Dose Dependent Effect

We studied the effect of benzodiazepine anxiolytic phenazepam after the predator presentation to Danio rerio. The test of novelty was used: the fish was placed first in a beaker with a dissolved pharmacological substance (or H2O) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of freezing were measured. It is shown that, in response to the novelty of tank, the fish are reacted by submerging to the bottom, increasing the frizing, and reducing the number of movements to the upper half of the novel tank. After phenazepam administration, the fish were not only in the lower, but also in the upper part of the novel tank. The average path length did not change significantly in the range of doses used. The number and time of the frizing, as well as the time spent in the lower part of the novel tank, decreased more than 2 times compared to the control group of animals and showed a dose-dependent effect. The number of movements to the upper part of the novel tank for the experiment increased significantly from 1 in the control to 57 after phenazepam in a dose of 1 mg/l. At the same time, the number of movements of fish to the upper part of the novel tank significantly increased more than 2 times from 3th min of the experiment with the use of phenazepam in a dose of 1 mg/l. Predator presentation (Hypsophrys nicaraguensis) caused an increase in the number of freezing (temporary immobilization) and a decrease in the length of the trajectory of movement in the novel tank as compared with the Danio rerio control group. Phenazapam at a dose of 1 mg/l removed the effects of a predator, while exhibiting a typical effect: the number of movements to the upper part of the tank during the experiment significantly increased to 30; the time at the bottom of the tank was halved. It was concluded that the novelty stress test and the test with a predator are highly sensitive for studying anxiety-phobic reactions in Danio rerio.

scholarly journals Effect of novelty stress on behavioral responses of Danio rerio and assessment of dose-dependent effects of anxiolytics of benzodiazepine structure with phenazepam as an example

2017 ◽  
Vol 15 (3) ◽  
pp. 57-63 ◽  
Author(s):  
Petr D. Shabanov ◽  
Viktor A. Lebedev ◽  
Andrei A. Lebedev ◽  
Eugenii R. Bychkov
Keyword(s):  
Danio Rerio ◽  
Path Length ◽  
Stress Test ◽  
Behavioral Responses ◽  
Anxiolytic Effect ◽  
Control Group ◽  
The Novel ◽  
Pharmacological Substance ◽  
First Time ◽  
Dose Dependent

The effect of benzodiazepine anxiolytic phenazepam in Danio rerio was investigated. Previously, Danio rerio showed the effects of other anxiolytics, dia_zepam and chlordiazepoxide. The analysis of the anxiolytic effect of phenazepam in Danio rerio was carried out for the first time. Methods. A stress test on novelty situation was used: a fish was placed first in a beaker with a dissolved pharmacological substance (or water) and then into a novel tank for 6 min, where the trajectory, the path length, the number of movements to the upper part of the novel tank, the number and time of the pattern of “freezing” for each min of the experiment were measured. Results. In response to the novelty of tank, the fish was shown to react by submerging to the bottom, increasing the freezing, and reducing the number of movements to the upper half of the novel tank. After phenazepam exposure (administration), the fish was not only in the lower, but also in the upper part of the novel tank. The average path length did not change significantly in the range of the doses used. The number and time of the freezing, as well as the time spent in the lower part of the novel tank, 2-fold decreased compared to the control group of animals and showed a dose-dependent effect. The number of movements to the upper part of the novel tank for the experiment increased significantly from 1 in the control to 57 after phenazepam in a dose of 1 mg/l. When analyzing the dynamics of the parameters for each min, it was shown that the time of the fish in the lower part of the novel tank decreased from 3th min of the experiment with the use of phenazepam in a dose of 0.5 mg/l. At the same time, the number of movements of fish to the upper part of the novel tank significantly increased more than 2 times from 3th min of the experiment with the use of phenazepam in a dose of 1 mg/l. Conclusion. The described method to study behavioral responses of Danio rerio on novelty stress is high sensitive in comparison with traditional behavioral methods of studing tranquilizers. The prospect of using Danio rerio as animal model in behavioral pharmacology is significant and does not concede research on rodents.

Enlargement of cerebrospinal fluid spaces in long-term benzodiazepine abusers

1987 ◽  
Vol 17 (4) ◽  
pp. 869-873 ◽  
Author(s):  
C. Schmauss ◽  
J.-C. Krieg
Keyword(s):  
Low Dose ◽  
Matched Control ◽  
Control Group ◽  
High Dose ◽  
Withdrawal Therapy ◽  
The Mean ◽  
Dose Dependent ◽  
Dose Dependent Effect ◽  
Age And Sex

SynopsisIn 17 benzodiazepine (BDZ) dependent in-patients a CT scan was performed before initiation of withdrawal therapy. The evaluation of the ventricular to brain ratio (VBR) by standardized and computerized measurements revealed significantly higher mean VBRs for both high-and low-dose BDZ-dependent patients compared to the mean VBR of an age- and sex-matched control group. In addition, the mean VBR of high-dose BDZ-dependent patients (N = 8) was significantly higher than the mean VBR of low-dose BDZ-dependent patients (N = 9). This difference could not be accounted for by the age of the patients or duration of BDZ-dependency and, therefore, suggests a dose-dependent effect of BDZs on the enlargement of internal CSF-spaces. On the other hand, higher values for the width of external CSF-spaces were found to be related to increasing age of the patients and duration of BDZ-dependency.

scholarly journals Dose-dependent effect of betamethasone on the articular cartilage (experimental study)

2021 ◽  
Vol 27 (1) ◽  
pp. 80-86
Author(s):  
A.N. Nuriakhmetov ◽  
◽  
I.F. Akhtiamov ◽  
D.E. Tsyplakov ◽  
A.M. Abdullah ◽  
...  
Keyword(s):  
Subchondral Bone ◽  
Inflammatory Cell ◽  
Left Knee ◽  
Knee Joints ◽  
Control Group ◽  
Rabbit Knee ◽  
Frequency Of Use ◽  
The Right ◽  
Dose Dependent ◽  
Dose Dependent Effect

Introduction Glucocorticosteroid injections have been widely used in clinical practice. Betamethasone is one of the agents of this group of drugs. Its efficacy and therapeutic effect with intra-articular administration are undeniable. There are special instructions on the dosage and frequency of use of the drug but unfortunately there are cases of its wrong administration. There is also an evidence of an adverse effect on cartilage both of the drug itself and its combination with local anesthetics. Aim Evaluation of the results of different weekly intra-articular protocols of betamethasone administration on histological preparations of rabbit knee joints. Methods Histological preparations of the right knee joints of three groups of rabbits were studied: after one, three, and six administrations of betamethason per week and the control intact left knee joints. Results Histological preparations of the control group and the group with a single weekly administration of the drug did not have any changes in the structure of diarthrosis. Dystrophic and necrotic changes affecting all morphological components were observed in the joints of animals that received intra-articular injections of betamethason three times a week (compared to a single injection, the area of dystrophy and necrosis of the cartilage was greater by 10.05 ± 0.75 % (p < 0.05), of subchondral bone by 8.11 ± 0.5 % (p < 0.001), and of synovium by 6.25 ± 0.32 % (p < 0.05). The group with six injections of the drug per week had the most pronounced changes. The area of necrotic changes of the cartilage was greater by 6.39 ± 0.75 % than in the group with three injections per week (p < 0.001), of subchondral bone by 11.18 ± 0.5 % (p < 0.001), of synovium by 6.12 ± 0.32 % (p < 0.001). Discussion Inflammatory cell infiltration of joint structures was absent in all cases. It indicates an aseptic nature of tissue necrosis. Evidence has been obtained between the increase in the frequency of intra-articular injections of betamethasone and the severity of dystrophic and necrotic changes in all morphological components of the joint.

scholarly journals The effectiveness of different regimens of testosterone gel therapy in men with androgen deficiency

2020 ◽  
Vol 10 (1) ◽  
pp. 57-60
Author(s):  
Andrey V. Kuzmenko ◽  
Timur A. Gyaurgiev ◽  
Yulia Yu. Bakutina ◽  
Alena Yu. Zarubayco
Keyword(s):  
Behavioral Therapy ◽  
Control Group ◽  
Total Testosterone ◽  
Androgen Deficiency ◽  
Testosterone Deficiency ◽  
Duration Of Treatment ◽  
Basic Therapy ◽  
Testosterone Gel ◽  
Dose Dependent ◽  
Dose Dependent Effect

The results of androgen replacement therapy with the appointment of a transdermal gel with testosterone in patients with androgen deficiency were presented. 90 men with testosterone deficiency (12 nmol/L) and impaired erectile function were observed. The average age of patients was 58 5.2 years. Patients were divided into 3 groups. Patients of the 1st (control) group underwent basic behavioral therapy, the 2nd group received basic therapy with testosterone gel for a dose of 50 mg, the 3rd group received basic therapy with testosterone gel at a dose of 100 mg. The duration of treatment was 6 months. The use of testosterone in the form of a transdermal gel led to a significant increase in the content of total testosterone in both patients of the 2nd (50 mg) and 3rd groups (100 mg). A dose-dependent effect was noted, in patients of the 3rd group the level of testosterone was significantly higher than in patients 2nd group. An increase in testosterone was accompanied by a decrease in FSH and LH levels.

scholarly journals Robust behavioural effects in response to acute, but not repeated, terpene administration in Zebrafish (Danio rerio)

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Joshua Szaszkiewicz ◽  
Shannon Leigh ◽  
Trevor J. Hamilton
Keyword(s):  
Danio Rerio ◽  
Aromatic Compounds ◽  
Open Field Test ◽  
Sedative Effect ◽  
Repeated Exposure ◽  
The Novel ◽  
Treatment Groups ◽  
Behavioural Effects ◽  
Therapeutic Value ◽  
Dose Dependent

AbstractTerpenes are fragrant aromatic compounds produced by a variety of plants, most notably cannabis and hops. With increasing legalization of cannabis there is a need to better understand the behavioural effects of terpenes and ultimately their therapeutic value. Our study investigated the dose-dependent impact of three terpenes (limonene 0.25, 0.5, 0.75%; β-myrcene 0.001, 0.01, 0.1%; and 0.0001, 0.001, 0.00125% linalool) on zebrafish (Danio rerio) behaviour when exposed both acutely and repeatedly over a 7-day period. Anxiety-like behaviour, boldness, and locomotion were assessed using the open field test and the novel object approach test. In the acute dosing experiment, limonene and β-myrcene exposed groups demonstrated a significant decrease in locomotion, a decrease in anxiety-like behaviour, and an increase in boldness, while linalool treatment groups demonstrated only minor alterations in locomotion. Moreover, repeated exposure to limonene (0.39%) or β-myrcene (0.0083%) for a seven day period did not result in any significant behavioural effects. In conclusion, our study provides support for an anxiolytic and sedative effect in zebrafish in response to acute limonene and β-myrcene exposure that is no longer present after one week of repeated exposure.

scholarly journals Study of thermo-regulation as a worsening marker of experimental sepsis in an animal model

2020 ◽  
Vol 28 ◽  
Author(s):  
André Luiz Thomaz de Souza ◽  
Marcelo Eduardo Batalhão ◽  
Evelin Capellari Cárnio
Keyword(s):  
Body Temperature ◽  
Saline Solution ◽  
Control Group ◽  
Experimental Sepsis ◽  
Plasma Lactate ◽  
Model Method ◽  
Sepsis Model ◽  
Plasma Nitrate ◽  
Dose Dependent ◽  
Dose Dependent Effect

Objective: to analyze variations in body temperature and in plasma nitrate and lactate concentrations in rats submitted to the experimental sepsis model. Method: a total of 40 rats divided equally into five groups. The induction of endotoxemia was performed with intravenous administration of lipopolysaccharide, 0.5 mg/Kg, 1.5 mg/Kg, 3.0 mg/Kg, and 10 mg/Kg, respectively. The control group received 0.5 mL of saline solution. The experiment lasted six hours, with evaluations performed at 0 (baseline data), 2nd, 4th, and 6thhours. Results: The animals that received doses up to 3.0 mg/kg showed a significant increase in body temperature compared to the group with 10 mg/kg, which showed a decrease in these values. The increase in plasma nitrate and lactate concentrations in the groups with lipopolysaccharide was significantly higher than in the group that received the saline solution and was correlated with the increase in body temperature. Conclusion: the variations in body temperature observed in this study showed the dose-dependent effect of lipopolysaccharide and were correlated with the increase in the concentrations of nitrate and plasma lactate biomarkers. The implications of this study are the importance of monitoring body temperature, together with the assessment of these pathophysiological markers, which suggest worsening in the prognosis of sepsis.

scholarly journals Tribenuron methyl exposure inhibits oogenesis in zebrafish Danio rerio (Hamilton, 1822)

2017 ◽  
Vol 64 (2) ◽  
Author(s):  
C. Akbulut ◽  
B. Ozturk ◽  
A. Uzun ◽  
N. D. Yon
Keyword(s):  
Danio Rerio ◽  
Aquatic Ecosystems ◽  
Control Group ◽  
Fallow Land ◽  
Aquatic Life ◽  
Histological Architecture ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Histopathological Effects ◽  
Tribenuron Methyl

Tribenuron methyl is a herbicide that is used to control annual and perennial dicots in cereals and fallow land. Pesticides can access aquatic ecosystems via groundwater and affect water quality and aquatic life. Our study evaluated histopathological effects of tribenuron methyl on ovary of the zebrafish Danio rerio (Hamilton, 1822). Ovary of the fishes in control group not exposed to the herbicide showed normal histological architecture. In the fishes exposed to tribenuron methyl, vacuolisation, edema and dysmorphism were recorded. Significant decrease in the number of primary and mature oocytes as well as dose dependent increase in the number of atretic oocytes were recorded in fishes exposed to tribenuron methyl.

scholarly journals Reversible Albumin-Binding GH Possesses a Potential Once-Weekly Treatment Profile in Adult Growth Hormone Deficiency

2016 ◽  
Vol 101 (3) ◽  
pp. 988-998 ◽  
Author(s):  
Michael Højby Rasmussen ◽  
Jurgita Janukonyté ◽  
Marianne Klose ◽  
Djordje Marina ◽  
Mette Tanvig ◽  
...  
Keyword(s):  
Adverse Events ◽  
Dose Level ◽  
Gh Deficiency ◽  
Dose Range ◽  
Control Group ◽  
Albumin Binding ◽  
Dependent Manner ◽  
Weekly Treatment ◽  
Dose Dependent ◽  
Treatment Profile

Abstract Context: NNC0195-0092 is a reversible, albumin-binding GH derivative, developed for once-weekly administration. Objectives: The objective of the study was to evaluate safety, local tolerability, pharmacodynamics, and pharmacokinetics of multiple, once-weekly doses of NNC0195-0092, compared with daily GH. Design and Setting: This was a phase 1, randomized, open-label, active-controlled, multiple-dose, dose-escalation trial. Patients: Thirty-four GH-treated adult subjects (male, n = 25) with GH deficiency participated in the study. Interventions and Main Outcome Measures: Subjects were sequentially assigned into four cohorts of eight subjects, randomized within each cohort (3:1) to once-weekly NNC0195-0092 (n = 6) for 4 weeks (0.02, 0.04, 0.08, and 0.12 mg/kg) or daily injections of Norditropin NordiFlex (n = 2) for 4 weeks with a dose replicating the pretrial dose of somatropin. A safety assessment was performed prior to initiating treatment at the next dose level of NNC0195-0092. Daily GH treatment was discontinued 14 days before the trial start. Blood samples were drawn for assessment of safety, pharmacokinetics, pharmacodynamics (IGF-1 and IGF-binding protein-3) profiles, and immunogenicity studies. Results: Numbers of adverse events were similar at the dose levels of 0.02, 0.04, and 0.08 mg/kg NNC0195-0092 vs daily injections of Norditropin NordiFlex, whereas the number of adverse events was greater at the highest dose level of NNC0195-0092 (0.12 mg/kg). NNC0195-0092 (area under the curve[0–168h]) and peak plasma concentration) increased in a dose-dependent manner, and a dose-dependent increase in IGF-1 levels was observed. IGF-1 profiles were elevated for at least 1 week, and for the 0.02-mg/kg and 0.04-mg/kg NNC0195-0092 doses, the observed IGF-1 levels were similar to the levels for the active control group. Conclusion: Four once-weekly doses of NNC0195-0092 (dose range 0.02–0.12 mg/kg) administered to adult patients with GH deficiency were well tolerated, and IGF-1 profiles were consistent with a once-weekly treatment profile. No clinically significant safety and tolerability signals causally related to NNC0195-0092 were identified, nor were any immunogenicity concerns revealed.

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