scholarly journals Proposal of open field test as a model of varenicline pharmacokinetic study in rats

Author(s):  
Julia Zaccarelli-Magalhães ◽  
Thaisa Meira Sandini ◽  
André Rinaldi Fukushima ◽  
Helenice De Souza Spinosa

Varenicline is a medication used for smoking treatment that acts as a partial agonist for nicotinic cholinergic receptors α4β2 and α3β4 and as a total agonist of receptor α7 in the central nervous system. Pharmacokinetic is important information for medications that acts in the central nervous system. This kind of assay is commonly done by expensive and complex analytical techniques. Therefore, the aim of this study was to evaluate the possibility of using the open field test as a pharmacokinetic model for varenicline in male rats exposed to a single dose of varenicline. Male rats received a single dose orally (gavage) of three different concentrations of varenicline: 0.03 (therapeutic dose for humans), 0.1 and 0.3 mg/kg or water (control group). The open field observations were recorded 30 min, 1, 2, 4, 6, 24, 48, 72 h and 7 days after the administration of varenicline or water. The results showed alterations in locomotion and rearing frequencies, as well as in immobility time observed in open field, which is consistent with this drug’s plasma peak. Consequently, this behavioral test apparently can be considerate as a model for pharmacokinetic evaluation of varenicline.

2016 ◽  
Vol 33 (S1) ◽  
pp. s289-s289
Author(s):  
Y. Zhang ◽  
F. Liu ◽  
Z. Dai ◽  
B. Wu ◽  
Q. Wu

ObjectiveTo observe the effect of Qing Huan Ling and (or) risperidone on locomotor activity and explorative behavior of schizophrenia mice model by open field test.MethodsSeventy kunming mice were randomly divided into 5 groups, one group as blank group. The rest groups ip MK-801 continuously 14 day, then randomly numbered: model group, risperidone group, Qing Huan Ling group and risperidone combined Qing Huan Ling group. Ig give corresponding drugs for each group 4 weeks, observe the change of locomotor activity and explorative behavior by open field test.ResultsAfter Ig 4 weeks, compared with the blank group, there were no obvious difference in locomotor activity and explorative behavior between risperidone group, Qing Huan Ling group and the combined group. Compared with the model group, risperidone had statistics meaning in the repression of explorative behavior (P < 0.05),the combined group has statistics meaning in the repression of locomotor activity and explorative behavior (78.92 ± 36.18 m vs. 186.92 ± 41.08 m, P < 0.01).ConclusionQing Huan Ling regulate the central nervous system of schizophrenia mice model; when combined with risperidone, it restrain the central nervous system of schizophrenia mice model and the effect is stronger than risperidone alone.Disclosure of interestThe authors have not supplied their declaration of competing interest.


2016 ◽  
Vol 3 (6) ◽  
pp. 257-262
Author(s):  
Augusto Pascual Italo Gargiulo ◽  
Santiago Marquez Herrero ◽  
Esteban Romanowicz ◽  
Manuel Alejandro Guevara ◽  
Adriana Ines Landa ◽  
...  

Gamma-Amino Butyric Acid (GABA) is the main inhibitor neurotransmitter of the Central Nervous System (CNS). Its peripheral administration has been matter of discussion. On the one hand, it has been reported that it does not cross the Blood-Brain Barrier (BBB), and, on the other hand, it has been associated with multiple therapeutic regimens and supplements by peripheral administration. The aim of the present study is to elucidate the possibility of a central sedative effect when administered peripherally. An experimental cohort of 90-day-old Holtzman male rats weighing 240-270 g was used. It was divided into 2 groups: saline-controls (n = 9) and GABA treated rats (12.5 mg/kg, n = 9). Both groups were intraperitoneally injected. The motor behavioral patterns displayed in the Opto Varimex (OVM) were studied. Vertical, horizontal, ambulatory and non-ambulatory movements and the number of movements were recorded in an automated way. Horizontal movements constitute the integration of ambulatory and non-ambulatory movements. Student t test was used comparing groups. In this experiment, there were non-significant downward trends in vertical, ambulatory, non-ambulatory and number of movements. Ambulatory and non-ambulatory tendencies acquired significance when treated together as horizontal movements (p < 0.05). We may conclude that peripheral administration of GABA produced a decrease of the horizontal movements in the open field test. It may be interpreted as a sedative effect, suggesting a passage of GABA through BBB, with central effects. However, there are several alternative possibilities to explain present findings. Other experiments will elucidate the implications or scope of the present findings.


1970 ◽  
Vol 1 (1) ◽  
pp. 44-50 ◽  
Author(s):  
Md Ashraful Alam ◽  
Nazmuj Slahin ◽  
Riaz Uddin ◽  
SM Raquibul Hasan ◽  
Raushanara Akter ◽  
...  

Analgesic and central nervous system depressant activity of the methanol extract of Achyranthes aspera Linn. was assessed by using acetic acid induced writhing test, thiopental sodium induced sleeping time determination, hole cross test and open field test in albino mice. The extract (250 and 500mg/kg) showed a dose dependent inhibition of writhing response generation by acetic acid compared to reference drug diclofenac sodium (50mg/kg). Methanol (70%) extract of Achyranthes aspera (500 mg/kg) also produced rapid onset and maximized the duration of sleeping time when administered with thiopental sodium. The extract also decreased the motor activity and exploratory behavior of mice in hole cross and open field test. The overall experimental results suggest the analgesic and central nervous system depressant activity of the methanolic extract of Achyranthes aspera and justify its use in folkloric remedies. Key Words: Achyranthes aspera, Analgesic activity, Central nervous system depressant activity. doi:10.3329/sjps.v1i1.1807 S. J. Pharm. Sci. 1(1&2): 44-50


Author(s):  
Р. В. Антіпова ◽  
Т. Є. Комісова ◽  
А. Є. Сак

Recently, the influence of various origins fats on the morphofunctional and biochemical characteristics of the organism has been actively studied, however, their possible influence on higher nervous activity and behavior has been mostly overlooked. The aim of the research was to study the dynamics of behavioral changes in rats after the long-term consumption of fats differing in origin. The behavior of adult male rats was explored by the open field test for three days on the basis of the indicators of their research and emotional activity after 60 days of consumption of fats of various origins (palm oil, refined sunflower oil, margarine) at a rate of 3 mg/kg. The obtained experimental data show that when rats consume fats differing in origin for a long time, their navigation research behavior in terms of horizontal and vertical activity and the number of hole visits does not differ significantly, both when retested in the open field and compared with the control group. However, it was found that their emotional activity (according to the manifestations of autonomic reactions of defecation and grooming) has changed as the prolonged consumption of used fats causes a change in the level of anxiety in male rats. The long-term consumption of palm oil is accompanied by a tendency to increase bowel movements as well as the number and duration of grooming acts, both in re-testing and compared with the control group. The male rats that had consumed margarine for a long time, on the contrary, demonstrated a decrease in the level of anxiety. In comparison with the control group and during testing, they showed a reduction in the manifestations of grooming and defecation. During three days of observation, the indicators of emotional activity of the rodents that had consumed refined oil for a long time stayed almost unchanged and did not differ from those of the control group.


2015 ◽  
Vol 156 (30) ◽  
pp. 1221-1225
Author(s):  
László István Gerecsei ◽  
Ágota Ádám

Introduction: The designer drug methylenedioxypyrovalerone is a frequently used psychoactive drug of abuse. Aim: The aim of this study was to determine the effect of methylenedioxypyrovalerone, administrated from the 8th to the 14th day of the gestation, on the development of central nervous system and on the behaviour of offspring mice. Method: Pregnant mice were treated during this period either with subcutaneous injection of 1×10 mg/kg body weight methylenedioxypyrovalerone or vehicle (saline). Maternal behaviour (pup retrieval test), locomotor activity (open field test) and motor coordination (grip strength test) of dams were evaluated. Locomotor activity at the 7th and 21st postnatal day (open field test) and motor coordination at the 21st postnatal day (grip strength test) were examined. Results: Reduced maternal behaviour among treated animals was observed. There was no difference in the results of the open field test between treated and control groups. Decrease of locomotor activity was observed in the pups of the methylenedioxypyrovalerone treated dams. Conclusions: The results suggest that cathinones (in particular methylenedioxypyrovalerone) may adversely affect neural integrity of the developing central nervous system. Orv. Hetil., 2015, 156(30), 1221–1225.


2018 ◽  
Vol 17 (2) ◽  
pp. 132-143 ◽  
Author(s):  
Mehmet Eray Alcigir ◽  
Halef Okan Dogan ◽  
Begum Yurdakok Dikmen ◽  
Kubra Dogan ◽  
Sevil Atalay Vural ◽  
...  

Background & Objective: Aroclor 1254 is a widespread toxic compound of Polychlorinated Biphenyls (PCBs), which can create significant nervous problems. No remedies have been found to date. The aim of this study was to reveal the damage that occurs in the central nervous system of rat pups exposed to Aroclor 1254 in the prenatal period and to show the inhibiting effect of curcumin, which is a strong anti-oxidant and neuroprotective substance. Method: The study established 3 groups of adult female and male Wistar albino rats. The rats were mated within these groups and the offspring rats were evaluated within the group given Aroclor 1254 only (n=10) and the group was given both Aroclor 1254 and curcumin (n=10) and the control group (n=10). The groups were compared in respect of pathomorphological damage. The immunohistochemical evaluation was made of 8-hydroxdeoxyguanosine (8-OHdG), 4-hydroxynoneal (4HNE), myelin basic protein (MBP) expressions and TUNEL reaction. The biochemical evaluation was made of the changes in the TAS-TOS and Neuron Specific Enolase (NSE) levels. Damage was seen to have been reduced with curcumin in the 8OHdG and TUNEL reactions, especially in the forebrain and the midbrain, although the dosage applied did not significantly change TAS and TOS levels. Consequently, it was understood that Aroclor 1254 caused damage in the central nervous system of the pup in the prenatal period, and curcumin reduced these negative effects, particularly in the forebrain and the midbrain. Conclusion: It was concluded that curcumin could be a potential neuroprotective agent and would be more effective at higher doses.


2016 ◽  
Vol 2016 ◽  
pp. 1-8
Author(s):  
Qianli Tang ◽  
Qiuyan Jiang ◽  
Suren R. Sooranna ◽  
Shike Lin ◽  
Yuanyuan Feng ◽  
...  

To observe the effects of electroacupuncture on pain threshold of laboring rats and the expression of norepinephrine transporter andα2 adrenergic receptor in the central nervous system to determine the mechanism of the analgesic effect of labor. 120 pregnant rats were divided into 6 groups: a control group, 4 electroacupuncture groups, and a meperidine group. After interventions, the warm water tail-flick test was used to observe pain threshold. NE levels in serum, NET, andα2AR mRNA and protein expression levels in the central nervous system were measured. No difference in pain threshold was observed between the 6 groups before intervention. After intervention, increased pain thresholds were observed in all groups except the control group with a higher threshold seen in the electroacupuncture groups. Serum NE levels decreased in the electroacupuncture and MP groups. Increases in NET andα2AR expression in the cerebral cortex and decreases in enlarged segments of the spinal cord were seen. Acupuncture increases uptake of NE via cerebral NET and decreases its uptake by spinal NET. The levels ofα2AR are also increased and decreased, respectively, in both tissues. This results in a decrease in systemic NE levels and may be the mechanism for its analgesic effects.


2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Eduardo Navarro ◽  
S. J. Alonso ◽  
R. Navarro

Elenine is the aglycone of elenoside, a cytotoxic arylnaphthalene lignan (NSC 644013-W/1) derived fromJusticia hyssopifolia. (Family: Acanthaceae). Elenoside is a β-D-glucoside, with a similar chemical structure to etoposide, exhibiting central depressant activity. In the present study, elenine was given to mice and rats at doses of 10, 20, and 40 mg/kg. Acute toxicity (24 h) and general behaviour in mice was studied as well as its effects on muscular relaxant activity, locomotor activity (Varimex test), and the open-field test and were compared with 10 mg/kg of chlorpromazine. Elenine produced a reduction in the permanence time in muscular relaxant activity (traction test). Spontaneous activity was lower in the Varimex test. The ambulation and rearing were lower compared with the control group, and an increase in boluses was observed in the open-field test. Thus, it can be concluded that elenine has central sedative effects at lower doses than those used with elenoside and has a possible application in conditions of anxiety.


Author(s):  
Puja Jha ◽  
Seema Bhalerao ◽  
Mrunal Dhole

Background: Anxiety affects around 7.3% of the total population worldwide. Benzodiazepines are preferred anxiolytic agents and are still frequently used in spite of the side effect profile including muscle relaxation, memory disturbances, sedation, physical dependence. Arnica montana, a traditional herb is known to possess significant anxiolytic effect at the dose of 100mg/kg. In this study, Arnica montana has been compared for the first time with alprazolam, a most commonly used anxiolytic drug.Methods: Forced swim test was used to induce anxiety. Anxiolytic action of study drugs which were given orally, was evaluated using Open field test (OFT) in healthy wistar rats of either sex. Behavior of rats, locomotion and number of squares crossed was recorded. Rats were divided into four groups with eight rats in each group. Study groups were Group I Control; Group II Alprazolam 0.08mg/kg; Group III Arnica montana extract (AME) 100mg/kg; Group IV AME + Alprazolam group 100mg/kg+0.08mg/kg. Statistical analysis was done using ANOVA followed by Tukey’s test (p<0.05).Results: Increase in frequency of rearing was significant (p<0.05) in AME group and highly significant (p<0.001) in Alprazolam and combination group in comparison to control. Decrease in frequency of grooming was highly significant (p<0.001) in Alprazolam and combination group. AME also showed significant (p<0.05) decrease in grooming activity.Conclusions: Arnica montana extract showed anxiolytic activity and can be used as an add on drug after further studies and validation in the treatment of anxiety disorders.


2021 ◽  
Vol 11 (11) ◽  
pp. 249-265
Author(s):  
B. Lobasyuk ◽  
L. Bartsevich ◽  
A. Zamkovaya

Justification. Mental retardation is a persistent decrease in human cognitive activity against the background of organic damage to the central nervous system. Neurophysiological diagnostics, in particular electroencephalography (EEG), most adequately reflects the morpho-functional state of the central nervous system, which is the basis of the mechanisms of mental activity, and the originality of the bioelectrical activity of the brain can be considered as the main indicator that determines a decrease in the level of intellectual development and, thereby, characterizes this state. This provision actualizes the search for highly informative indicators of the originality of the bioelectrical activity of the brain in children with intellectual disabilities. Purspose. With the use of periodometric analysis investigate EEG’s indicators and interhemispheric asymmetry of rhythms amplitudes in MR patients. Materials and methods. The EEG was recorded in a state of calm wakefulness with closed eyes with Neuron-Spectrum-2 electroencephalograph. Differences in indicators were tracked using the calculation of the coefficient of compliance (CC), EEG functional asymmetry coefficients in amplitude were determined, too. Results. It was revealed that in MR patients the amplitudes of the rhythms were greater than in healthy subjects. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. Duration indices in the delta, theta and alpha ranges of the EEG in mental retardation compared with the control group were increased, and the indices of the duration of beta rhythms - decreased. When analyzing FMPA in MR persons it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices. Conclusions 1. With mental retardation, the amplitudes of the rhythms were greater than in healthy people. The greatest increase was determined in theta rhythm in the anterior temporal and posterior temporal leads in the left hemispheres. 2. The indices of duration in the delta, theta and alpha ranges of the EEG of MR subjects were increased, and the indices of the duration of beta rhythms – decreased. 3. When analyzing FMPA in MR persons, it turned out that in right-handers the negativeness of FMPA indices increased, and in left-handers there was an increase in the positivity of FMPA indices.


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