Browsing by Subject "Rats"

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  • Oinio, Ville; Sundström, Mikko; Bäckström, Pia; Uhari-Väänänen, Johanna; Kiianmaa, Kalervo; Raasmaja, Atso; Piepponen, Petteri (2018)
    Comorbidity with gambling disorder (GD) and alcohol use disorder (AUD) is well documented. The purpose of our study was to examine the influence of genetic alcohol drinking tendency on reward-guided decision making behavior of rats and the impact of dopamine releaser D-amphetamine on this behavior. In this study, Alko alcohol (AA) and Wistar rats went through long periods of operant lever pressing training where the task was to choose the profitable of two options. The lever choices were guided by different-sized sucrose rewards (one or three pellets), and the probability of gaining the larger reward was slowly changed to a level where choosing the smaller reward would be the most profitable in the long run. After training, rats were injected (s.c.) with dopamine releaser D-amphetamine (0.3, 1.0 mg/kg) to study the impact of rapid dopamine release on this learned decision making behavior. Administration of D-amphetamine promoted unprofitable decision making of AA rats more robustly when compared to Wistar rats. At the same time, D-amphetamine reduced lever pressing responses. Interestingly, we found that this reduction in lever pressing was significantly greater in Wistar rats than in AA rats and it was not linked to motivation to consume sucrose. Our results indicate that conditioning to the lever pressing in uncertain environments is more pronounced in AA than in Wistar rats and indicate that the reinforcing effects of a gambling-like environment act as a stronger conditioning factor for rats that exhibit a genetic tendency for high alcohol drinking.
  • Otsomaa, Leena; Levijoki, Jouko; Wohlfahrt, Gerd; Chapman, Hugh; Koivisto, Ari-Pekka; Syrjänen, Kaisa; Koskelainen, Tuula; Peltokorpi, Saara-Elisa; Finckenberg, Piet; Heikkilä, Aira; Abi-Gerges, Najah; Ghetti, Andre; Miller, Paul E; Page, Guy; Mervaala, Eero; Nagy, Norbert; Kohajda, Zsófia; Jost, Norbert; Virág, László; Varró, András; Papp, Julius Gy (2020)
    BACKGROUND AND PURPOSE: The lack of selective sodium-calcium exchanger (NCX) inhibitors has hampered the exploration of physiological and pathophysiological roles of cardiac NCX 1.1. We aimed to discover more potent and selective drug like NCX 1.1 inhibitor. EXPERIMENTAL APPROACH: A flavan series-based pharmacophore model was constructed. Virtual screening helped us identify a novel scaffold for NCX inhibition. A distinctively different NCX 1.1 inhibitor, ORM-11372, was discovered after lead optimization. Its potency against human and rat NCX 1.1 and selectivity against other ion channels was assessed. The cardiovascular effects of ORM-11372 were studied in normal and infarcted rats and rabbits. Human cardiac safety was studied ex vivo using human ventricular trabeculae. KEY RESULTS: ORM-11372 inhibited human NCX 1.1 reverse and forward currents; IC(50) values were 5 and 6 nM respectively. ORM-11372 inhibited human cardiac sodium 1.5 (I(Na) ) and hERG K(V) 11.1 currents (I(hERG) ) in a concentration-dependent manner; IC(50) values were 23.2 and 10.0 μM. ORM-11372 caused no changes in action potential duration; short-term variability and triangulation were observed for concentrations of up to 10 μM. ORM-11372 induced positive inotropic effects of 18 ± 6% and 35 ± 8% in anaesthetized rats with myocardial infarctions and in healthy rabbits respectively; no other haemodynamic effects were observed, except improved relaxation at the lowest dose. CONCLUSION AND IMPLICATIONS: ORM-11372, a unique, novel, and potent inhibitor of human and rat NCX 1.1, is a positive inotropic compound. NCX inhibition can induce clinically relevant improvements in left ventricular contractions without affecting relaxation, heart rate, or BP, without pro-arrhythmic risk.
  • Itkonen, Suvi T.; Pajula, Elina T.; Dowling, Kirsten G.; Hull, George L. J.; Cashman, Kevin D.; Lamberg-Allardt, Christel J. E. (2018)
    Ultraviolet-irradiated yeast (Saccharomyces cerevisiae) can be used to biofortify bakery products with vitamin D, but in bread, it was not effective in increasing serum 25-hydroxyvitamin D [25(OH)D] in humans, possibly because of the low digestibility of the yeast matrix. We investigated the effects of vitamin D-2-rich intact yeast cells and their separated fraction, yeast cell walls, which we hypothesized to provide vitamin D-2 in a more bioavailable form, on serum 25(OH)D and its metabolites in growing female Sprague-Dawley rats (n = 54) compared to vitamin D-2 and D-3 supplements (8 treatment groups: 300 or 600 IU vitamin D/d, and a control group, 8-week intervention). The D-3 supplement groups had the highest 25(OH)D concentrations, and the vitamin D-2 supplement at the 600-IU dose increased 25(OH)D better than any yeast form (P <.001 for all, analysis of covariance, adjusted for body weight). There were no significant differences between the yeast forms at the same dose (P > .05). Serum 24,25-dihydroxyvitamin D (a vitamin D catabolite) concentrations and the trend in the differences between the groups were in line with 25 (OH)D (P <.001 for all). The 24,25-dihydroxyvitamin D to 25(OH)D ratio between the D-2 supplement and the yeast groups did not differ (P > .05). These findings do not support the hypothesis: the ability of the different ultraviolet-treated vitamin D-2-containing yeast forms to increase 25(OH)D did not differ, and the poor bioavailability of vitamin D-2 in the yeasts compared D-3 or D-2 supplements could not be explained by the increased vitamin D catabolism in the yeast-treated groups. (C) 2018 Elsevier Inc. All rights reserved.
    The exposure to amoxicillin has been associated with molar incisor hypomineralization. This study aimed to determine if amoxicillin disturbs the enamel mineralization in in vivo experiments. Fifteen pregnant rats were randomly assigned into three groups to received daily phosphatase-buffered saline or amoxicillin as either 100 or 500 mg/kg. Mice received treatment from day 13 of pregnancy to day 40 postnatal. After birth, the offsprings from each litter continued to receive the same treatment according to their respective group. Calcium (Ca) and phosphorus (P) content in the dental hard tissues were analyzed from 60 upper first molars and 60 upper incisors by the complexometric titration method and colorimetric analysis using a spectrophotometer at 680 nm, respectively. Lower incisors were analyzed by X-ray microtomography, it was measured the electron density of lingual and buccal enamel, and the enamel and dentin thickness. Differences in Ca and P content and electron density among the groups were analyzed by one-way ANOVA. There was no significant difference on enamel electron density and thickness among the groups (p > 0.05). However, in incisors, the higher dose of amoxicillin decreased markedly the electron density in some rats. There were no statistically significant differences in Ca (p = 0.180) or P content (p = 0.054), although the higher dose of amoxicillin could affect the enamel in some animals. The amoxicillin did not significantly alter the enamel mineralization and thickness in rats. © 2020