Evaluation of long-term administration of the antioxidant stobadine on exploratory behaviour in rats of both genders

Anxiety and mood disorders have become very significant affections in the last decades. According to WHO at least one mental disease occurred per year in 27% of EU inhabitants (more than 82 mil. people). It is estimated that by 2020, depression will be the main cause of morbidity in the developed countries. These circumstances call for research for new prospective drugs with anxiolytic and antidepressive properties exhibiting no toxicity and withdrawal effect and possessing beneficial properties, like antioxidant and/or neuroprotective effects. The aim of this study was to obtain information about psychopharmacological properties of pyridoindole derivatives SMe1EC2 and SMe1M2, using non-invasive behavioral methods in rats.The battery of ethological tests (open field, elevated plus-maze, light/dark box exploration, forced swim test) was used to obtain information about anxiolytic and antidepressant activity of the pyridoindole derivatives. The substances were administered intraperitoneally 30 minutes before the tests at doses of 1, 10 and 25 mg/kg.In the behavioral tests, SMe1EC2 was found to exert anxiolytic activity in elevated plus maze with no affection of locomotor activity. The highest dose of SMe1M2 increased the time spent in the lit part of the Light/Dark box, however this result was influenced by inhibition of motor activity of the rats. Similar findings were observed also in elevated plus-maze, although these results were not statistically significant.In conclusion, from the results of our study it is evident that both pyridoindoles acted on the CNS. In the highest dose, SMe1M2 was found to possess rather sedative than anxiolytic or antidepressant activity.

Section: Discussionmentioning

confidence: 99%

Anxiolytic activity of pyridoindole derivatives SMe1EC2 and SMe1M2: behavioral analysis using rat model

Sedláčková¹,

Ponechalová²,

Ujházy³

et al. 2011

“…Despite the fact that coping behavior in novelty could be a sensitive indicator of behavioral toxicity, complex habituation analyses are omitted in most of the neurotoxicity studies. In our previous studies, we thoroughly investigated habituation of exploratory behavior in neurobehavioral toxicities, and the results obtained are of relevance for evaluating behavioral processes in the open field in a more complex way (Dubovický et al ., 1997a , b ; 1999a , b ; 2004 ).…”

Section: Basic Procedures Of Neurobehavioral Testingmentioning

confidence: 99%

“…In our current experimental practice we test animals repeatedly. Repeated testing in an open field test enables a more complex evaluation of the data obtained, such as habituation processes (Dubovický et al ., 1997a ; 1999a ). In a series of experiments in which we investigated the effect of neonatal anoxia on motor activity in the open field at the time around weaning (single anoxia induced on postnatal days 2, 3, 4 or 5 in duration of 10, 15, 20 or 25 min), we found a decrease in motor activity compared to controls in all time intervals.…”

Section: Most Important Issues To Be Taken Into Account In Neurobehavmentioning

confidence: 99%

Evaluation of developmental neurotoxicity: some important issues focused on neurobehavioral development

Dubovický¹,

P²,

Ujházy³

et al. 2008

Exposure of the developing organism to industrial chemicals and physical factors represents a serious risk factor for the development of neurobehavioral disorders, such as attention-deficit hyperactivity disorder, autism and mental retardation. Appropriate animal models are needed to test potentially harmful effects and mechanisms of developmental neurotoxicity of various chemical substances. However, there are significant human vs. rat differences in the brain developmental profile which should be taken into account in neurotoxicity studies. Subtle behavioral alterations are hard to detect by traditional developmental toxicity and teratogenicity studies, and in many cases they remain hidden. They can however be revealed by using special behavioral, endocrine and/or pharmacological challenges, such as repeated behavioral testing, exposure to single stressful stimulus or drugs. Further, current neurobehavioral test protocols recommend to test animals up to their adulthood. However some behavioral alterations, such as anxiety-like behavior or mental deficiency, may become manifest in later periods of development. Our experimental and scientific experiences are highly suggestive for a complex approach in testing potential developmental neurotoxicity. Strong emphasis should be given on repeated behavioral testing of animals up to senescence and on using proper pharmacological and/or stressful challenges.

“…(for review see Juranek et al , 2010). Series of toxicological studies including acute, subchronic and chronic toxicity tests with STB on various animals concluded that STB was safe and did not possess any severe adverse effects within the potential pharmacological range (Gajdošíková et al , 1995, Dubovický et al , 1999). However, a non-specific α-adrenolytic (Kvaltinova et al , 1986) and H 1 -antihistaminic side effects were reported (Lukovic & Machova, 1988).…”

Section: Introductionmentioning

confidence: 99%

Effect of a novel stobadine derivative on isolated rat arteries

Broskova

Sotníková

et al. 2013

The antioxidant and reactive-oxygen-species-scavenging activity of stobadine has been demonstrated in previous studies. Recently, chemical modification of this leading structure led to the synthesis of other pyridoindole derivatives with significantly increased intrinsic antioxidant efficacy. Further structural modifications of stobadine provided the opportunity to increase bioavailability and attenuate unwanted side effects, such as α-adrenolytic activity. The aim of the work was to evaluate the direct effect of a novel pyridoindole, SMe1EC2, on the vascular wall ex vivo. The vasomotor effect of SMe1EC2 (1×10–8–1×10–4 mol/l) was measured on isolated and pressurized rat cerebral and coronary arterioles using video-microscopy. The effect of SMe1EC2 (1×10–6 and 1×10–5 mol/l) on high potassium-, phenylephrine- or serotonin-induced contraction or acetylcholine-induced relaxation was also determined in aortic rings. We found that SMe1EC2 (1×10–8–1×10–4 mol/l) elicited significant dilatations in both cerebral and coronary arterioles (max dilatation: 25±8% and 18±5% respectively). Yet, SMe1EC2 (1×10–6 and 1×10–5 mol/l) did not influence the tone of aortic rings nor did it affect high potassium-, phenylephrine- or serotonin -induced contractions and acetylcholine-induced relaxation. Thus SMe1EC2 was able to dilate resistance arteries but did not affect aortic contractility. It is likely that SMe1EC2 does not possess α1-adrenolytic and anti-serotoninergic activity in the vascular wall.