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Stephen B Dunnett - One of the best experts on this subject based on the ideXlab platform.
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analysis of skilled forelimb movement in rats the single pellet reaching Test and Staircase Test
Current protocols in protein science, 2012Co-Authors: Alexander Klein, Stephen B DunnettAbstract:Brain damage, stroke, and neurodegenerative diseases such as Parkinson's or Huntington's disease can cause severe motor deficits in skilled forelimb use in both humans and rats. These deficits are typically analyzed in a reach-to-eat paradigm. Skilled reaching in rats has been found to be a good model of human skilled reaching. Therefore, rats serve as an excellent tool to monitor the development of deficits after neurological insults or changes after medical intervention. The following protocols comprise two different Tests of rat skilled reaching. The single pellet reaching Test is a paradigm that involves detailed rating and analysis of qualitative aspects of the reaching movement itself. The Staircase Test is an objective, high-throughput reaching task that allows reaching success (number of pellets eaten) to be investigated in multiple rats at the same time. Both Tests have been used extensively to investigate motor deficits and effects of treatment.
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Staircase skilled reaching Test
Reference Module in Neuroscience and Biobehavioral Psychology#R##N#Encyclopedia of Movement Disorders, 2010Co-Authors: Stephen B DunnettAbstract:The Staircase Test evaluates skilled reaching abilities in rodents. In particular, it provides a direct quantitative measure of motor skills involving reaching, grasping under proprioceptive feedback, and retrieval of food in rats and mice. The Staircase Test is objective, simple, and efficient, without requiring rating or video analysis by the investigator.
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the Staircase Test of skilled reaching in mice
Brain Research Bulletin, 2001Co-Authors: Alison Lambie Baird, Alicia Meldrum, Stephen B DunnettAbstract:Abstract The “Staircase” Test has become established for measurement of side-specific deficits in coordinated paw reaching in rats, and has been shown to reveal impairments on the contralateral side following unilateral lesions in a wide range of motor structures of the brain. As mice become more widely used in behavioural neuroscience, we have scaled down the Staircase reaching Test for application to this latter species. We here validate the Test in C57BL/6J mice by (a) establishing the optimal dimensions of the apparatus, (b) comparing the effects of Test parameters including sex, Test duration, levels of deprivation and alternative reward pellets, and (c) demonstrating contralateral deficits after aspirative lesions of the motor cortex. Differences between mice and rats in normal performance of the task are noted. The Staircase Test provides a simple objective Test of skilled motor function that allows measurement of lateralised effects without unduly constraining the animal, and which may prove as useful for mice as has previously been demonstrated in rats.
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the Staircase Test a measure of independent forelimb reaching and grasping abilities in rats
Journal of Neuroscience Methods, 1991Co-Authors: C P Montoya, L J Campbellhope, K D Pemberton, Stephen B DunnettAbstract:A novel reaching Test for the rat has been developed to assess the independent use of forelimbs in skilled reaching and grasping tasks. The apparatus is a plexiglas box with a removable baited double Staircase. Food pellets are placed on the Staircase and presented bilaterally at 7 graded stages of reaching difficulty to provide objective measures of side bias, maximum forelimb extension and grasping skill. In the present experiment, the apparatus was used to assess the reaching performance of rats following unilateral lesions of the sensorimotor cortex, unilateral lesions of the posterior cortex or bilateral lesions of the olfactory bulbs. The task has the advantage of objective over rating measurement, and the simplicity of the apparatus permits many animals to be Tested concurrently.
Marika Vali - One of the best experts on this subject based on the ideXlab platform.
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effects of litter origin and weight on behaviour of outbred nih s mice in plus maze and Staircase Tests
Scandinavian Journal of Laboratory Animal Science, 2008Co-Authors: K Okva, Marika Vali, Aavo Lang, Timo Nevalainen, Kari Mauranen, Paavo PokkAbstract:The objective of this study was to investigate the effects of litter and weight on the behavior of mice. Male outbred NIH/S mice from 8 litters were randomly distributed among 6 cages and subjected to the plus-maze and Staircase Tests. The litter from which the animals had originated had a significant effect on the behavior of mice in the plus-maze Test; furthermore addition of the covariates final weight and weight gain had no effect on significance or explanatory value. It is proposed that litter origin might influence the adaptation processes, the development of social status and consequently, the behavior of mice. Differences attributable to litter were not observed in the Staircase Test, but when both weight parameters were added as covariates this proved to be significant. Though the source of these litter-related differences remains to be clarified, these differences do have a significant effect on the behavior of mice. Therefore they need to be considered since knowledge of the litter where the outbred mice originated can partly explain differences in the behavior of the animals. The comparison of models showed that incorporation of the natural features of the animals (as derived from their biological origin) into a calculation can help rationalise the results; and provide ample opportunities for discussion and understanding of this complex issue.Â
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effects of nitric oxide synthase inhibitors 7 ni l name and l noarg in Staircase Test
Archives of Medical Research, 2002Co-Authors: Paavo Pokk, Marika ValiAbstract:Abstract Background The objective of the study was to investigate the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI), N G -nitro-L-arginine (L-NOARG), and N G -nitro-L-arginine methyl ester (L-NAME) on the behavior of mice in the Staircase Test. Methods NOS inhibitors 7-NI (20–120 mg/kg), L-NOARG (20 and 40 mg/kg), and L-NAME (20 and 40 mg/kg) were administered intraperitoneally (i.p.) 30 min prior to the Staircase Test. Staircase Test consisted of placing a mouse in an enclosed Staircase with five steps and recording the number of rearings made and the number of steps climbed during a 3-min period. Results 7-NI and L-NOARG did not have a significant effect on the behavior of mice in the Staircase Test. L-NAME caused a decrease in the number of rearings without changes in the number of steps taken. Conclusions NOS inhibitor L-NAME but not 7-NI or L-NAME induced an anxiolytic effect in the Staircase Test.
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small platform stress increases exploratory activity of mice in Staircase Test
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2001Co-Authors: Paavo Pokk, Marika ValiAbstract:Abstract 1. Small platform (SP) stress was induced by placing mice on small platforms (3.5 cm diameter) surrounded by water for 24 h. This model contains several factors of stress like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. 2. The Staircase Test consisted of placing a mouse in an enclosed Staircase with 5 steps and recording (1) the number of steps and (2) rearings made during 3 min. SP stress increased the exploratory activity of mice in the Staircase Test as evidenced by an increase in the number of steps and rearings made 3. In control mice diazepam (0.25 and 0.5 mg/kg) induced an anxiolytic effect in the Staircase Test as evidenced by a decrease in the number of rearings without changes in the number of steps. In SP stressed mice the anxiolytic effect of diazepam was not seen and the sedative effect as evidenced by a decrease in the number of steps was more pronounced. Buspirone at a dose of 1.0 mg/kg did not have effect on the behaviour of control or SP stressed mice in the Staircase Test. 4. To study possible diurnal variations the Staircase Test was carried out at 3 different times of a day (08:00, 14:00, 20:00) with control and SP stressed mice. The exploratory activity of control mice in the Staircase Test gradually increased from 08:00 to 20:00 as evidenced by an increased number of steps and rearings made. SP stress increased the exploratory activity of mice irrespective of the time of Testing. 5. In conclusion, on the basis of these data the authors can propose that SP stress increases the exploratory activity of mice in the Staircase Test and induces a hyposensitivity of mice to the anxiolytic effect of diazepam. The effect of SP stress on the behaviour of mice in the Staircase Test is not caused by the disruptance of diurnal rhythms.
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the effects of flumazenil ro 15 4513 and β ccm on the behaviour of control and stressed mice in the Staircase Test
Journal of Psychopharmacology, 2001Co-Authors: Paavo Pokk, Marika ValiAbstract:The effects of flumazenil, Ro 154513 and beta-CCM in the Staircase Test were studied in control and small platform (SP) stressed mice. SP stress was induced by placing mice on small platforms (3.5 cm in diameter) surrounded by water for 24 h. This model contains several factors of stress, such as rapid eye movement sleep deprivation, isolation, immobilization and falling into the water. The Staircase Test consisted of placing a mouse in an enclosed Staircase with five steps and recording: (i) the number of rearings and (ii) steps made during 3 min. SP stress increased the exploratory activity of mice in the Staircase Test as demonstrated by an increase in the number of rearings and steps made. In control mice flumazenil (2.0 and 10.0 mg/kg), Ro 15-4513 (1.0 and 3.0 mg/kg) and beta-CCM (1.0 and 2.0 mg/kg) exerted an anxiogenic effect that was demonstrated by an increase in the number of rearings without significant changes in the number of steps. Similar to control mice, flumazenil induced an anxiogenic effect in SP stressed mice as demonstrated by an increase in the number of rearings. However, the sedative effect of flumazenil as demonstrated by a decrease in the number of steps made was more pronounced in SP stressed mice. In the SP stressed mice, the anxiogenic effect of Ro 15-4513 and beta-CCM was masked by their strong sedative effect and a decrease in both measures of exploratory activity (number of rearings and number of steps). These data suggest that SP stress induces hypersensitivity to the sedative effect of flumazenil, Ro 15-4513 and beta-CCM in the Staircase Test.
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the effects of the nitric oxide synthase inhibitor 7 nitroindazole on the behaviour of mice after chronic ethanol administration
Alcohol and Alcoholism, 2001Co-Authors: Paavo Pokk, Eve Sepp, Vitali Vassiljev, Marika ValiAbstract:The effects of the nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI) on the behaviour of mice after chronic and acute ethanol administration were studied. Male albino mice received ethanol by inhalation for 25 days. The plus-maze and Staircase Tests were carried out with control, ethanol-intoxicated and ethanol-withdrawn mice (7.5 h after the end of ethanol administration). The administration of NOS inhibitor 7-NI [20.0 mg/kg, intraperitoneally (i.p.)] 60 min or 7.5 h before the plus-maze Test induced an anxiolytic effect in control mice. Chronic ethanol administration induced an anxiolytic, and ethanol withdrawal an anxiogenic, effect in mice. The administration of 7-NI (20.0 mg/kg, i.p.) caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. 7-NI had no effect on the behaviour of control mice in the Staircase Test. Chronic ethanol administration increased, and ethanol withdrawal decreased, the locomotor activity of mice in the Staircase Test. Likewise, in the plus-maze Test, administration of 7-NI caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. In additional experiments, vehicle or 7-NI (20.0–120.0 mg/kg, i.p.) were administered 30 min before ethanol (3.0 g/kg, i.p.). 7-NI dose-dependently increased the duration of ethanol-induced sleep and inhibited ethanol clearance. On the basis of these data we can propose that the NO system has no major role in behavioural changes caused by ethanol withdrawal. At the same time NOS inhibitors can cause synergistic CNS depression with ethanol.
Carlos Alexandre Netto - One of the best experts on this subject based on the ideXlab platform.
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skilled forelimb reaching in wistar rats evaluation by means of montoya Staircase Test
Journal of Neuroscience Methods, 2009Co-Authors: Aline De Souza Pagnussat, Stella Maris Michaelsen, Matilde Achaval, Carlos Alexandre NettoAbstract:Experimental animals have been used as models for several neurological disorders; their performance in behavioral Tests is useful in determining the success of lesion repair procedures and assessing functional recovery. The Staircase Test is a behavioral Test that consists in reaching for food inside a special box and allows for a sensitive measure of skilled reaching by each limb in an independent manner. In most laboratories in the south of Brazil, Wistar rats are used for the study of experimental stroke, hypoxia and peripheral neuropathy, but most studies with the Staircase Test have used other strains such as Sprague-Dawley and Long-Evans. Because skilled reaching, grasping and performance can differ among strains, the purpose of the present study was to characterize the performance of Wistar rats in the Staircase Test and determine the effect of median and ulnar nerve crush. Our results with Wistar rats on the Staircase Test showed that: similar to other strains, Wistar animals can display high performance after 2 weeks of training; the number of animals that attained the inclusion criterion increased by 10% with longer times of training; the stricter criterion of 15 pellets taken can be adopted as study inclusion criterion; the Test has an unquestionable value in assessing lateralized deficits, as evidenced by the lack of performance deficit of the non-manipulated forelimb at any time point. These results extend the understanding about the performance of Wistar rats in the Staircase Test, which will be used for the best training and research using this strain.
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the skilled forelimb reaching in wistar rats evaluation by montoya Staircase Test
Progress in motor control VI, 2007Co-Authors: Aline De Souza Pagnussat, Stella Maris Michaelsen, Carlos Alexandre NettoAbstract:Experimental animals, mainly rats and mice, have been used in several studies of neurological diseases. Their performance in behavioral Tests are useful to evaluate the success of specific effects of lesions procedures as well as to access the pattern of functional recovery after different types of treatment (Biernaskie & Corbett, 2001; Whishaw et al., 2003; Windle et al., 2006). Despite the widespread use of animal models in functional rehabilitation, sometimes little consideration is given to lineage selection and related effects on skilled forelimb use. The Staircase Test was initially described by Montoya et al., 1991 and allows a sensitive measure of bilateral skilled reaching. The task consists in reach for food inside a special box with a central platform and adjacent Staircases. The forelimb ability is assessed by means of the record of pellets eaten, dropped and remaining on the steps. The purpose of present study was the characterization and evaluation of Staircase Test for inbred albino rat Wistar before and after brachial plexus crushing. Fifty eight male adult Wistar rats housed under standard laboratory conditions were used. They were trained during three weeks before the surgery, 2 trials of 15 minutes per day (totalizing 24 trials). Then, they were reTested 24 hours and 7 days after the crushing procedure at the same daily frequency and time. Results demonstrated no forelimb preference to do the reaching, 56,9% of animals preferred the right while 25,9% of animals used more the left and 17,2% did not show paw preference. The scores with right paw (11,8?3,5 ) were very similar those obtained with left (11,1?3,6), although more pellets could be reached with the preferred paw (12,6?3,2) when compared with the not preferred one (10,2?3,5; p=0,0002). As to reach the criterion of a minimum of 18 pellets eaten, 10,5? 4,4 trials were necessary, nevertheless just 69% of animals attained that performance. This analyze will be useful to perform another trustworthy behavior studies with Wistar rats.
Guido Nikkhah - One of the best experts on this subject based on the ideXlab platform.
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colour coded pellets increase the sensitivity of the Staircase Test to differentiate skilled forelimb performances of control and 6 hydroxydopamine lesioned rats
Brain Research Bulletin, 2006Co-Authors: Verena Kloth, Alexander Klein, David Loettrich, Guido NikkhahAbstract:The Montoya Staircase Test has previously been used to study the skilled forelimb performance of mice and rats following lesions and cell implants in different parts of the central nervous system. Here we describe a modification of the original Test design which introduces differently coloured food pellets for each step, and present the results of the new and modified method. In this study unilaterally 6-hydroxydopamine (6-OHDA) lesioned rats and healthy control rats were used. The new evaluation of reaching and grasping movements takes into consideration the various levels of reaching difficulty. The coloured food pellets code for different steps of the Staircase. The comparison between the original versus the modified Test methods revealed significant differences most prominently on the lower steps. It is important to notice that the pattern of grasping movements in the hemiparkinsonian rats changes from precise reaching (prior to lesion) to shuffling and unsuccessfully trying to reach pellets. The observation of this change in behaviour would not have been obtained through the evaluation of the original Staircase Test. In summary, the modified Staircase Test introduces a colour-coded pellet system which obviously increases the Test sensitivity and discloses new insights into the skilled forelimb use in a rat model of Parkinson's disease. It may therefore become a valuable tool in future studies related to plasticity-induced changes in skilled forelimb reaching and grasping movements.
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differences in acquisition and full performance in skilled forelimb use as measured by the Staircase Test in five rat strains
Behavioural Brain Research, 1998Co-Authors: Guido Nikkhah, Christoph Rosenthal, Hansjurgen Hedrich, Madjid SamiiAbstract:Abstract Skilled forelimb use was examined in five different rat strains (DA/Ztm, LEW/Ztm-ci, LEW.1W/Ztm, SD/Ztm, SPRD/Ztm-Cu3) by means of the `Staircase Test', as originally described by Montoya et al. [20] (C.P. Montoya, H.L. Campbell, K.D. Pemberton, S.B. Dunnett, The `Staircase Test': A measure of independent forelimb reaching and grasping abilities in rats, J. Neurosci. Methods 36 (1991) 219–228). Strain-dependent differences were observed most prominently during the acquisition phase, and less pronounced, at the full performance level. SD/Ztm and DA/Ztm rat strains seemed to be particularly skilled in their forelimb use, although with varying levels of activity. Interestingly, significant differences in skilled forelimb movements were found between the related Sprague-Dawley derived and Lewis congenic rat strains. No clear-cut correlation was found between skilled forelimb use and basic nutrition-dependent measures, such as preTest body weight or weightloss during the Test period. Based on previous observations on strain-dependent behavioral variations it seems likely that the differences in skilled forelimb use, as observed in the present study, might be caused by morphological and/or functional strain-dependent alterations in the involved neuronal circuitries, such as motor cortex, caudate-putamen unit and mesotelencephalic dopamine system. However, they should also be considered as potentially influencing parameters in studies related to the behavioral effects of lesions and restorative therapies in the central nervous system.
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forelimb akinesia in the rat parkinson model differential effects of dopamine agonists and nigral transplants as assessed by a new stepping Test
The Journal of Neuroscience, 1995Co-Authors: Martin L Olsson, Guido Nikkhah, C Bentlage, Anders BjorklundAbstract:Methods for the assessment of akinesia in the unilateral rat Parkinson model have so far been lacking. The experiments reported here evaluate the usefulness of a new “stepping Test” to monitor forelimb akinesia in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the mesencephalic dopamine (DA) system, and to assess the ability of DA- receptor agonists and fetal DA neuron transplants to reverse these deficits. The 6-OHDA lesion induced marked and long-lasting impairments in the initiation of stepping movements with the contralateral paw. Systemic injections of low doses (chosen to be subthreshold for induction of rotation) of the mixed D1 and D2 receptor agonist apomorphine, the D1-selective agonist SKF 38393, and to a lesser extent also the D2-selective agonist quinpirole were effective in reversing these deficits. Similar effects was seen after a subrotational dose of L-dopa, whereas amphetamine had no effect. Fetal nigral transplants, implanted as multiple deposits in the ipsilateral caudate-putamen and substantia nigra, restored initiation of stepping to a similar degree as the DA agonists. Nigral grafts placed in substantia nigra alone were also effective, although the improvement was less pronounced. Apomorphine, at a dose effective in the lesion-only animals, had no additive effect in the grafted rats, whereas amphetamine appeared to further improve stepping in the rats with intranigral transplants. Identical experiments were performed on skilled forelimb use in the so- called Staircase Test. Interestingly, neither the DA agonist drugs nor the nigral transplants had any effects on the lesion induced deficits in this more complex task. The results show that forelimb stepping is a highly useful Test to monitor lesion-/and transplant-induced changes in forelimb akinesia, a behavioral parameter that may be analogous to limb akinesia and gait problems seen in patients with Parkinson9s disease.
Paavo Pokk - One of the best experts on this subject based on the ideXlab platform.
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effects of litter origin and weight on behaviour of outbred nih s mice in plus maze and Staircase Tests
Scandinavian Journal of Laboratory Animal Science, 2008Co-Authors: K Okva, Marika Vali, Aavo Lang, Timo Nevalainen, Kari Mauranen, Paavo PokkAbstract:The objective of this study was to investigate the effects of litter and weight on the behavior of mice. Male outbred NIH/S mice from 8 litters were randomly distributed among 6 cages and subjected to the plus-maze and Staircase Tests. The litter from which the animals had originated had a significant effect on the behavior of mice in the plus-maze Test; furthermore addition of the covariates final weight and weight gain had no effect on significance or explanatory value. It is proposed that litter origin might influence the adaptation processes, the development of social status and consequently, the behavior of mice. Differences attributable to litter were not observed in the Staircase Test, but when both weight parameters were added as covariates this proved to be significant. Though the source of these litter-related differences remains to be clarified, these differences do have a significant effect on the behavior of mice. Therefore they need to be considered since knowledge of the litter where the outbred mice originated can partly explain differences in the behavior of the animals. The comparison of models showed that incorporation of the natural features of the animals (as derived from their biological origin) into a calculation can help rationalise the results; and provide ample opportunities for discussion and understanding of this complex issue.Â
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effects of nitric oxide synthase inhibitors 7 ni l name and l noarg in Staircase Test
Archives of Medical Research, 2002Co-Authors: Paavo Pokk, Marika ValiAbstract:Abstract Background The objective of the study was to investigate the effects of the nitric oxide synthase (NOS) inhibitors 7-nitroindazole (7-NI), N G -nitro-L-arginine (L-NOARG), and N G -nitro-L-arginine methyl ester (L-NAME) on the behavior of mice in the Staircase Test. Methods NOS inhibitors 7-NI (20–120 mg/kg), L-NOARG (20 and 40 mg/kg), and L-NAME (20 and 40 mg/kg) were administered intraperitoneally (i.p.) 30 min prior to the Staircase Test. Staircase Test consisted of placing a mouse in an enclosed Staircase with five steps and recording the number of rearings made and the number of steps climbed during a 3-min period. Results 7-NI and L-NOARG did not have a significant effect on the behavior of mice in the Staircase Test. L-NAME caused a decrease in the number of rearings without changes in the number of steps taken. Conclusions NOS inhibitor L-NAME but not 7-NI or L-NAME induced an anxiolytic effect in the Staircase Test.
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small platform stress increases exploratory activity of mice in Staircase Test
Progress in Neuro-psychopharmacology & Biological Psychiatry, 2001Co-Authors: Paavo Pokk, Marika ValiAbstract:Abstract 1. Small platform (SP) stress was induced by placing mice on small platforms (3.5 cm diameter) surrounded by water for 24 h. This model contains several factors of stress like rapid eye movement (REM) sleep deprivation, isolation, immobilization and falling into the water. 2. The Staircase Test consisted of placing a mouse in an enclosed Staircase with 5 steps and recording (1) the number of steps and (2) rearings made during 3 min. SP stress increased the exploratory activity of mice in the Staircase Test as evidenced by an increase in the number of steps and rearings made 3. In control mice diazepam (0.25 and 0.5 mg/kg) induced an anxiolytic effect in the Staircase Test as evidenced by a decrease in the number of rearings without changes in the number of steps. In SP stressed mice the anxiolytic effect of diazepam was not seen and the sedative effect as evidenced by a decrease in the number of steps was more pronounced. Buspirone at a dose of 1.0 mg/kg did not have effect on the behaviour of control or SP stressed mice in the Staircase Test. 4. To study possible diurnal variations the Staircase Test was carried out at 3 different times of a day (08:00, 14:00, 20:00) with control and SP stressed mice. The exploratory activity of control mice in the Staircase Test gradually increased from 08:00 to 20:00 as evidenced by an increased number of steps and rearings made. SP stress increased the exploratory activity of mice irrespective of the time of Testing. 5. In conclusion, on the basis of these data the authors can propose that SP stress increases the exploratory activity of mice in the Staircase Test and induces a hyposensitivity of mice to the anxiolytic effect of diazepam. The effect of SP stress on the behaviour of mice in the Staircase Test is not caused by the disruptance of diurnal rhythms.
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the effects of flumazenil ro 15 4513 and β ccm on the behaviour of control and stressed mice in the Staircase Test
Journal of Psychopharmacology, 2001Co-Authors: Paavo Pokk, Marika ValiAbstract:The effects of flumazenil, Ro 154513 and beta-CCM in the Staircase Test were studied in control and small platform (SP) stressed mice. SP stress was induced by placing mice on small platforms (3.5 cm in diameter) surrounded by water for 24 h. This model contains several factors of stress, such as rapid eye movement sleep deprivation, isolation, immobilization and falling into the water. The Staircase Test consisted of placing a mouse in an enclosed Staircase with five steps and recording: (i) the number of rearings and (ii) steps made during 3 min. SP stress increased the exploratory activity of mice in the Staircase Test as demonstrated by an increase in the number of rearings and steps made. In control mice flumazenil (2.0 and 10.0 mg/kg), Ro 15-4513 (1.0 and 3.0 mg/kg) and beta-CCM (1.0 and 2.0 mg/kg) exerted an anxiogenic effect that was demonstrated by an increase in the number of rearings without significant changes in the number of steps. Similar to control mice, flumazenil induced an anxiogenic effect in SP stressed mice as demonstrated by an increase in the number of rearings. However, the sedative effect of flumazenil as demonstrated by a decrease in the number of steps made was more pronounced in SP stressed mice. In the SP stressed mice, the anxiogenic effect of Ro 15-4513 and beta-CCM was masked by their strong sedative effect and a decrease in both measures of exploratory activity (number of rearings and number of steps). These data suggest that SP stress induces hypersensitivity to the sedative effect of flumazenil, Ro 15-4513 and beta-CCM in the Staircase Test.
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the effects of the nitric oxide synthase inhibitor 7 nitroindazole on the behaviour of mice after chronic ethanol administration
Alcohol and Alcoholism, 2001Co-Authors: Paavo Pokk, Eve Sepp, Vitali Vassiljev, Marika ValiAbstract:The effects of the nitric oxide synthase (NOS) inhibitor 7-nitroindazole (7-NI) on the behaviour of mice after chronic and acute ethanol administration were studied. Male albino mice received ethanol by inhalation for 25 days. The plus-maze and Staircase Tests were carried out with control, ethanol-intoxicated and ethanol-withdrawn mice (7.5 h after the end of ethanol administration). The administration of NOS inhibitor 7-NI [20.0 mg/kg, intraperitoneally (i.p.)] 60 min or 7.5 h before the plus-maze Test induced an anxiolytic effect in control mice. Chronic ethanol administration induced an anxiolytic, and ethanol withdrawal an anxiogenic, effect in mice. The administration of 7-NI (20.0 mg/kg, i.p.) caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. 7-NI had no effect on the behaviour of control mice in the Staircase Test. Chronic ethanol administration increased, and ethanol withdrawal decreased, the locomotor activity of mice in the Staircase Test. Likewise, in the plus-maze Test, administration of 7-NI caused behavioural depression in ethanol-intoxicated mice, but had no effect on the behaviour of ethanol-withdrawn mice. In additional experiments, vehicle or 7-NI (20.0–120.0 mg/kg, i.p.) were administered 30 min before ethanol (3.0 g/kg, i.p.). 7-NI dose-dependently increased the duration of ethanol-induced sleep and inhibited ethanol clearance. On the basis of these data we can propose that the NO system has no major role in behavioural changes caused by ethanol withdrawal. At the same time NOS inhibitors can cause synergistic CNS depression with ethanol.