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EN
Telejko E., Maćkowiak J. and Wiśniewski K.: The effect of collagen degradation products (CDP) on the central dopaminergic system. Acta Physiol. Pol. The effect of collagen degradation products (CDP I - molecular weight circa 3000 D and CDP II - molecular weight circa 1200 D) on the central dopaminergic system was studied. Differences in the action of both these fractions in the apomorphine stereotypy test were noted; CDP I administered to rats in a dose of 5 µg just before application of the drug inducing the stereotypy enhanced the stereotypic behaviour of the animals whereas a dose of µg40 significantly inhibited such behaviour. CDP II, on the other hand, had no effect on this type of stereotypy. Both fractions given in doses of 15 and 40 µg enhanced the stereotypy induced by amphetamine. CDP I and CDP II (15 and 40 µg) administered 30 min before observation of the animals intensified the cataleptic action of haloperidol, whereas both fractions (CDP I and CDP II) when administered 45 min before observation reduced the catalepsy.
EN
BACKGROUND The eff ect of prenatal exposition of rats with copper on its level in the newborns’ organs and central dopaminergic system activity in adult rats was examined. MATERIAL AND METHODS Pregnant rats during entire time of pregnancy drank water with cupprum sulfuricum (CuSO4) where concentration of metal was 100 ppm. Control rats drank the water only without cuprum. After delivery water with metal was substituted with water only, and newborns stayed with their mothers till 21st day of life, then separated. In newborn copper content was estimated in the brain, liver and kidney. In adult rats the level of biogenic amines was measured in the brain and some behavioral studies were performed such as oral activity, stereotyped and yawning behavior, using central dopamine receptor agonists (SKF 38393, apomorphine, 7-OH-DPAT). RESULTS AND CONCLUSION Exposition of rats during intrauteral development (prenatal) with copper caused signifi cant increase concentration examined metal in the brain, liver and kidney of newborn rats. In adult rats signifi cant decrease of dopamine in the striatum was noticed in the rats pretreated with copper. Beside increase reactivity of the central dopamine D1 receptor reactivity was observed, and manifested by increased oral activity after SKF 38393 and stereotyped behavior after apomorphine apply. Additionally decreased reactivity of the central dopamine D3 receptor was manifested by decreased yawning behavior after 7-OH-DPAT injection. From above we concluded that copper can be one of the environmental agent which can aff ected of the central dopaminergic system in mammalians.
PL
WSTĘP Celem pracy było zbadanie wpływu ekspozycji miedzią szczurzyc w trakcie ciąży na zawartość metalu w tkankach noworodków a także na funkcję ośrodkowego układu dopaminergicznego u dorosłego potomstwa. MATERIAŁ I METODY Ciężarne samice przez cały okres ciąży piły wodę z dodatkiem siarczanu miedzi (CuSO4) w stężeniu metalu 100 ppm. Kontrolne szczurzyce piły wodę bez metalu. Z chwilą urodzenia roztwór miedzi zamieniano na wodę. Noworodki pozostawały z matkami do 21 dnia życia. U noworodków oznaczono zawartość miedzi w mózgu, wątrobie i nerkach. U dorosłych potomnych szczurów płci męskiej wykonano oznaczenia zawartości amin biogennych w mózgu oraz oceniono zachowanie jak aktywność ruchową pyska, stereotypię apomorfi nową i liczbę ziewnięć, spontaniczną jak też po podaniu agonistów ośrodkowych receptorów dopaminowych (SKF 38393, apomorfi na, 7-OH-DPAT). WYNIKI I WNIOSKI Prenatalna ekspozycja szczurów miedzią spowodowała znaczny wzrost zawartości metalu w mózgu, wątrobie i nerkach w porównaniu z kontrolą. U dorosłych szczurów narażonych w okresie rozwoju śródmacicznego na miedź wykazano obniżenie zawartości dopaminy w prążkowiu oraz wzrost reaktywności receptorów dopaminowych D1 manifestujący się nasileniem aktywności ruchowej pyska po podaniu SKF 38393 i nasileniem zachowania stereotypowego po podaniu apomorfi ny oraz obniżenie reaktywności receptorów dopaminowych D3 manifestujące się zmniejszeniem liczby ziewnięć po podaniu 7-OH-DPAT. Z powyższego wynika, że narażenia (ekspozycja) miedzią w okresie rozwoju śródmacicznego prowadzi do kumulacji metalu w tkankach noworodków a także trwałego zaburzenia funkcji ośrodkowego układu dopaminergicznego u ssaków.
EN
On the morning of the first day of pregnancy, Wistar rats were administered a single IP injection of either zinc sulfate (10.0 mg/kg) or saline. For the remainder of pregnancy, half the rats in each group then consumed filtered tap water while the other half consumed filtered tap water with 50 ppm of cadmium (CdCl₂ ). At eight weeks after birth, the behavioral profile of male offspring was assessed in the following way: Apomorphine (non-selective dopamine receptor agonist), (+)-7-hydroxy-2-(di-n-propylamino) tetralin (7-OH-DPAT) (D₃ agonist) and (+/-)-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzazepine-7,8-diol (SKF 38393) (D₁ agonist) were used to evaluate stereotyped behavior, yawning activity and oral movements – indices for these respective agonists. In addition, two dopamine receptor antagonists, haloperidol (D₂ antagonist) and 7-chloro-8-hydroxy3-methyl-1-phenyl-2,3,4,5-tetrahydro-(1H)-3-benzapine (SCH 23390) (D₁ antagonist) were used to evaluate cataleptogenic activity. Additional behavioral parameters studied were locomotor activity, irritability and reaction to a painful stimulus. Dopamine and its metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 3-methoxytyramine (3-MT) were quantified in the striatum, hippocampus and in the frontal cortex of the brain by means of HPLC/ED technique. In addition, cadmium levels were analyzed in the brain, liver, kidney and bone of newborn rats. Our results indicate that prenatal exposure of pregnant rats to cadmium produced alterations in the reactivity of central dopamine receptors and modulated the level of dopamine and its metabolites in the offsprings’ brains. A single injection of zinc, preceding cadmium consumption, attenuated some of the effects of cadmium on the offsprings’ dopaminergic system. Zinc also reduced cadmium deposition in the brain, kidney and bone, but enhanced its accumulation in liver. In summary, zinc may exert some neuroprotective effects against cadmium neurotoxicity.
EN
Organic mercury (CH3HgCl) with metal concentration 5 ppm in tap water was applied to rats suckling their newborn for the first 21 days of life. A second group of young rats took the mercury in their tap water 5 ppm from the 22nd to the 43rd day of postnatal life. Control rats drank tap water only. In 2-month-old male rats the following behavioral study was performed after saline or specific central dopamine receptor agonists and agonists apply (quinpirole, SKF-38393, haloperidol, SCH-23390): irritability, yawning behavior, oral activity, locomotion, exploratory activity, and catalepsy. In the striatum and frontal cortex of three examined groups the biogenic amines levels (DA, DOPAC, HVA, 3-MT, 5-HT, 5-HIAA, NA) were estimated by means of HPLC/ED technique, and DA and 5-HT turnover. The effect of quinpirole (a central dopamine D2 receptor agonists) was also examined on (3H)glucose uptake in discrete parts of the brain. It was shown that mercury affected behavioral changes after dopaminergic agents apply to adult animals when exposed in the period from the 22nd to 43rd day of postnatal development. Biochemical changes (biogenic amines level, turnover and (3H)glucose uptake) were more pronounced in adult animals exposed to mercury via mother's milk (1st to 21st day of life). In light of the above we conclude that early postnatal exposure of rats to organic mercury modulates activity of the central dopamine neurotransmitter system.
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