Place avoidance tasks as tools in the behavioral neuroscience of learning and memory.

Spatial navigation comprises a widely-studied complex of animal behaviors. Its study offers many methodological advantages over other approaches, enabling assessment of a variety of experimental questions and the possibility to compare the results across different species. Spatial navigation in laboratory animals is often considered a model of higher human cognitive functions including declarative memory. Almost fifteen years ago, a novel dry-arena task for rodents was designed in our laboratory, originally named the place avoidance task, and later a modification of this approach was established and called active place avoidance task. It employs a continuously rotating arena, upon which animals are trained to avoid a stable sector defined according to room-frame coordinates. This review describes the development of the place avoidance tasks, evaluates the cognitive processes associated with performance and explores the application of place avoidance in the testing of spatial learning after neuropharmacological, lesion and other experimental manipulations.

Stereoselective interactions of warfarin enantiomers with the pregnane X nuclear receptor in gene regulation of major drug-metabolizing cytochrome P450 enzymes.

BACKGROUND: Warfarin, an antagonist of vitamin K, is an oral coumarin anticoagulant widely used to control and prevent thromboembolic disorders. Warfarin is clinically available as a racemic mixture of R- and S-warfarin. The S-enantiomer has three to five times greater anticoagulation potency than its optical congener. Recently, vitamin K2 function has been proposed via the pregnane X receptor (PXR) in osteocytes. PXR acts as a xenobiotic sensor that controls expression of many genes involved in drug/xenobiotic metabolic clearance. OBJECTIVE: The aim was to examine whether enantiomers of warfarin stereoselectively interact with PXR to up-regulate main drug/xenobiotic-metabolizing enzymes of the cytochrome P450 superfamily. METHODS: Interactions of warfarin enantiomers with PXR were tested by gene reporter assays and time-resolved fluorescence resonance energy transfer technology (TR-FRET) ligand binding assay. Up-regulation of PXR-target gene mRNAs by warfarin enantiomers was studied using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in primary human hepatocytes. RESULTS: We found that R-warfarin interacts with the PXR nuclear receptor. Consistently, R-warfarin significantly induced CYP3A4 and CYP2C9 mRNAs in cultures of primary human hepatocytes or in LS174T intestinal cells. On the other hand, S-warfarin is a less potent inducer of PXR-target genes in human hepatocytes and activates PXR only at supraphysiological concentrations. In addition, we showed that racemic 10- and 4'-hydroxywarfarins are also highly potent PXR ligands and inducers of CYP3A4 and CYP2C9 mRNA in human hepatocytes. CONCLUSION: We showed that R-warfarin can significantly up-regulate major drug-metabolizing enzymes CYP3A4 and CYP2C9 in the liver and thus may cause drug-drug interactions (DDI) with co-administered drugs. The results warrant reconsideration of racemic warfarin usage in clinics.

[Noradrenaline and behavior]. / Noradrenalin a chování.

Noradrenaline exerts many effects and mediates a number of functions in living organisms. Recently, the essential role of noradrenaline in the central nervous system (CNS) has emerged. Noradrenaline affects behaviors of individuals including a modulation of vigilance, arousal, attention, motivation, reward, and also learning and memory. Almost all brain noradrenergic fibers arise in brainstem nuclei designated A1-A7 (approximately half of neurons belongs to the brainstem nucleus, locus coeruleus). The effects of noradrenaline are mediated by two distinct super-families of receptors, named alpha- and beta-adrenoceptors. They are further divided into subgroups exhibiting specific roles in modulating behavior and cognition of animals. Adrenoceptors are located on the periphery as well as in the CNS and selective alpha- and beta-agonists and antagonists are used to assess their function. The purpose of this review is to summarize the findings about anatomy and physiology of the noradrenergic system in the CNS and discuss the pharmacological effects on specific adrenoceptor types. This paper also shows the importance of noradrenaline to maintain the cognitive processes such as attention, perception, and particularly the memory consolidation and retrieval. Disruption of these processes may result in symptoms of neuropsychiatric diseases and neurodegeneration.

Degradation of polyesteramides during composting under standard and isothermal conditions.

Polyesteramides based on epsilon-caprolactam and epsilon-caprolactone differing in the content of ester-amide structural units were subjected to biodegradation - composting in a big compost pile under controlled conditions (controlled composting) and in small composters at a steady temperature of 60 degrees C (isothermal composting). Both types of composting resulted in degradation of the polyesteramides depending on copolymer composition, isothermal composting being more robust. The contribution of abiotic hydrolysis to the degradation of polyesteramides was studied at 60 degrees C in buffer solutions with pH 5.4, 7.4 and 8.4. The prevailing effect of abiotic hydrolysis over biological one was shown at 60 degrees C. Ester bonds in polyestramide chains were preferentially cleaved; therefore, the scope of degradation increased with the content of ester units in the copolymer.

Biodegradation of synthetic polymers by composting and fungal treatment.

Two types of copolymers--poly(ester-amide)s--by the anionic copolymerization of epsilon-caprolactam and epsilon-caprolactone, and aromatic-aliphatic copolyesters based on glycolyzed polyethylene terephthalate from used beverage bottles and epsilon-caprolactone were prepared. Biodegradation tests of these copolymers were performed by two methods, viz. composting under controlled conditions and treatment with ligninolytic fungi. Both methods resulted in degradation of the copolymers, composting being more robust. Out of fungal strains tested Inonotus hispidus degraded aromatic-aliphatic copolyesters most intensively.