Influence of Hole Localization on Local and Global Dynamic Response of Thin-Walled Laminated Cantilever Beam.

In this study, we discuss the effects of the diameter and position of a hole on the dynamic response of a thin-walled cantilever beam made of carbon-epoxy laminate. Eigen-frequencies and corresponding global and local eigen-modes were considered, where deformations of the beam wall were dominant, without significant deformation of the beam axis. The study was focused on the circumferentially uniform stiffness (CUS) beam configuration. The laminate layers were arranged as [90/15(3)/90/15(3)/90]T. The finite element method was employed for numerical tests, using the Abaqus software package. Moreover, a few numerical results of the structure's behaviour, with and without a hole, were verified experimentally. The experimental eigen-frequencies and the corresponding modes were obtained using an experimental modal analysis, comprising the LMS system with modal hammer. We found that the size and location of the hole affected the eigen-frequencies and corresponding modes. Furthermore, even a small hole in a beam could significantly change the shape of its local modes. The numerical and experimental results were observed to have high qualitative compliance.

Selection of Urbanized Areas by Magpie Pica pica in a Medium Size City in Poland.

The Magpie Pica pica occurs all over open agricultural areas in Poland, especially near human settlements (particularly in western Poland). The aim of this study was to estimate the size of the local Magpie population and characterize, in detail, nest site selection in a medium size city Górzów Wlkp. in the XXI century. For this study, the whole city was divided into a total of 114 squares of 1 × 1 km. Data were collected in spring 2014. A total of 474 Magpie pairs were recorded. The average density was 5.5 pairs/km2 (min = 0, max = 22 nests/square), in the non-urbanized habitat type-3.7 p/km2, and in the urbanized habitat type-13.5 p/km2. Magpie nests were found most often on Spruces Picea sp. and Poplars Populus sp. The mean height of the nest site was 11.5 m, while the mean height of trees used for nesting was 13.4 m. The type of tree arrangement most frequently used for nesting was tree rows (26.3%), followed by single trees (24.6%) and clusters of 4-10 trees (20.1%). The results for the Magpie's environmental preferences do not differ from the general patterns described earlier. The study shows that magpies can adapt to changing urbanization factors, and changes in the choice of conifers help the species to adapt to highly anthropogenic habitats.

How littered are birds' of prey nests? Study of two sympatric species.

Anthropogenic activity results in production of wastes, including litter in the environment. The problem of waste pollution is especially noticeable and usually discussed from the perspective of marine environments. It is significantly less addressed in terrestrial habitats, where the spatial dispersion of litter makes it difficult to assess the degree of pollution and its impact on the ecosystems. In this study, we present the problem of littering the terrestrial environments in the context of their inclusion in raptor nests, which are relatively rare elements of these ecosystems and because they comprise the top positions in their trophic chains, are exemplary bioindicators. During the breeding season we quantitatively and qualitatively assessed the anthropogenic debris present in the nests of 48 Back Kites (Milvus migrans) and Red kites (Milvus milvus). We found that the prevalence of litter in the nests was 100% for both species. The average number of litter items and average total area of litter recorded per nest was 31.3 and 0.44 m2, respectively and differed between species, where higher values were recorded for the Black Kite than for the Red Kite (53.1 vs. 23.8 and 0.54 m2 vs. 0.34 m2, respectively). Taking into account the average nest surface area of both studied species (0.33 m2 and 0.57 m2, respectively), obtained values indicate large littering of the studied nests. Furthermore, 71% of identified debris items were plastics which constituted 65% of the total surface of all recorded debris. Our study suggests a high availability of litter in the terrestrial habitats that constitute the breeding territories of the two sympatric study species.

Influence of Mechanical Couplings on the Dynamical Behavior and Energy Harvesting of a Composite Structure.

In this paper, the dynamical behavior of composite material is analyzed, including the energy harvesting effect. The composite is modeled by the Finite Element Method (FEM) and is made of pre-impregnate with a matrix of thermosetting epoxy resin reinforced with high-strength R-type glass fibers, and it is designed as a beam structure that is exposed to mechanical vibrations. The structure assumed the form of a beam with a substantially rectangular cross section. The couplings of motion occurring between mode shapes at properly selected fiber orientations are investigated. The beams with determined sets of composite layers and a coupling effect are used to recover electricity from the mechanical vibrations in the vicinity of the first resonance zone. The composite with a certain number of fiber glass layers has assumed an orientation relative to the beam axis. The new values found in this paper are the intensity of the coupling between the bending in the stiff and flexible directions of the beam for a chosen fiber layer stacking sequence. Additionally, the influence of layer configuration on the energy harvesting efficiency of the Macro-Fiber Composite (MFC) piezoelectric element is assessed.

Do agricultural environments increase the reproductive success of White Stork Ciconia ciconia populations in South-Western Poland?

As populations of White Stork Ciconia ciconia have decreased at different rates in Europe, the specific environmental drivers that influence breeding success are a matter of controversy. Here we use body size, blood, and environmental data of a total of 1226 stork nestlings of different ages from a total of 363 nests in three different habitats (meadows, forest-edges, open agricultural landscapes) in S-W Poland to ask whether: 1) natural grassland environments increase the reproductive output in comparison with agricultural landscapes, 2) nestlings from agricultural landscapes differ in health status from nestlings in more natural habitats, 3) differences in environmental stress translate into respective differences in reproductive output and health status of nestlings. There was no significant difference in age corrected body mass and in the temporal increase in nestling mass between the study sites. Clutch sizes were highest and age corrected total clutch mass lowest at the meadow sites while agricultural and woodland sites did not significantly differ. Hemoglobin and red blood cell content were lowest and white blood cell and blood antioxidant concentrations were highest in the meadows indicating higher degrees of environmental stressors. These blood parameters varied strongly among study years. Our study does not confirm that agricultural landscapes are less suited for stork breeding success. We even find some indication of a better health status of nestlings in agricultural environments that might compensate smaller clutch sizes. Our data indicate that reproductive output is multifaceted. As we found some indication of a trade-off between clutch size and health status we argue that only multiple metrics of reproductive success are able to assess the long-term effect of habitat choice on fitness.

Ticks (Acari: Ixodida) on birds (Aves) migrating through the Polish Baltic coast.

Seasonal bird (Aves) migration between breeding and wintering areas, often located on different continents, can facilitate the spreading of tick species (Acari: Ixodida) and of tick-borne pathogens. The aim of the study was to analyse the occurrence of ticks dispersed by birds migrating along the Polish Baltic coast during spring and autumn migration. Field research was conducted at the bird ringing station in Wicie, located on the middle of the Polish Baltic coast, in 2011 and 2012 during spring and autumn migration. A total of 2657 birds from 45 species was examined. The most common species inspected were European robin (Erithacus rubecula) (63.3%), song thrush (Turdus philomelos) (5.13%), and goldcrest (Regulus regulus) (4.5%). Overall, 3129 ticks belonging to six species were collected: Ixodes ricinus (1650 larvae, 1390 nymphs and 1 male), Ixodes frontalis (20 larvae, 20 nymphs), Ixodes arboricola (35 larvae), Dermacentor reticulatus (1 larva), and Haemaphysalis punctata (1 nymph). Ten larvae and one nymph could only be identified to the genus level Ixodes. Ticks were located on various parts of the head: on the corner of the beak (75.0%), near the eyes (14.6%), on the chin (4.4%), near the ears (4.4%), on the neck (1.1%), and in the beak (0.5%). The overall tick prevalence was 40.5%. The highest prevalence was for bird species feeding on the ground, covering a medium distance to wintering grounds and migrating at night. Statistically significant differences between the number of ticks and the sex of the host species were detected in blackbirds: males carried more parasites than females, both, during spring and autumn migration. The fact that I. ricinus and other ticks parasitize birds migrating through Poland extends the possibility of the spread of tick-borne diseases.

Linking land cover satellite data with dietary variation and reproductive output in an opportunistic forager: Arable land use can boost an ontogenetic trophic bottleneck in the White Stork Ciconia ciconia.

Determining how the progressive loss of resources due to agricultural intensification and habitat degradation affect individual fitness and population persistence is a matter of urgency. Here we explored three major questions in order to extend knowledge of the relationship between reproduction rate, diet and energy intake in White Storks Ciconia ciconia based both on our own analysis of pellets and landscape properties sampled in 52 nests in south-western Poland, and published literature data. (1) How many individual prey items are needed to meet the daily energy requirements of nestlings over the brood rearing period? (2) How do the dietary patterns vary under different habitat conditions and what is the spatial scale responsible for these relationships? (3) Is reproductive output related to variations in landscape traits, and is diet variability related to intraspecific competition resulting from colonial breeding? In our estimation, the energy requirements of nestlings during the brood rearing period showed that the most profitable invertebrate prey items were Orthoptera and earthworms. Owing to the nestlings' gape-size constraint (precluding consumption of vertebrate prey items of the size of Common Voles), these most likely comprise the staple diet enabling survival during the first 20 days of life. The total energy content across all the pellets was a simple function (a negative correlation) of %arable land within a distance of 5 km around the nests. White Storks from nests of high-productivity pairs (with 3-4 fledglings and less %arable around) consumed equal %biomasses of invertebrate and vertebrate prey, while invertebrates prevailed in the diet of the low-productivity pairs. Our results suggest that a two-level ontogenetic trophic bottleneck may explain the low productivity of White Stork pairs in simplified landscapes with predominant arable land use. As a result of this, parent birds are unable to satisfy the growing energy demands of nestlings (1) by gathering a sufficient volume of abundant small-sized prey (early nestlings) and (2) by delivering energetically more profitable vertebrate prey at the time of the diet switch.

Data exploration on diet, and composition, energy value and functional division of prey items ingested by White Storks Ciconia ciconia in south-western Poland: Dietary variation due to land cover, reproductive output and colonial breeding.

The dataset presented in this data paper supports "Linking land cover satellite data with dietary variation and reproductive output in an opportunistic forager: Arable land use can boost an ontogenetic trophic bottleneck in the White Stork Ciconia ciconia" (Orlowski et al. 2019) [1]. Analysis of data on diet and prey composition based on an investigation of 165 pellets of White Storks Ciconia ciconia sampled from 52 nests showed that their diet was based primarily on 'eurytopic prey' (embracing taxa from grassland and a variety of non-cropped habitats), the biomass contribution of which in the diet was disproportionately (3-4-fold) higher than the percentage of available corresponding habitats. Similarly, prey items from water/wetland sites prevailed over the availability of corresponding habitats. The opposite pattern characterized prey taxa from arable habitats and forests, the contribution of which was lower than the availability of the corresponding habitats. The total energy content per pellet (calculated by summing the energy content of all individual prey items across one specific prey group) was the most strongly correlated with the biomass of Orthoptera, thereafter with that of mammals, other vertebrates, earthworms and other invertebrates, but not with the biomass of Coleoptera. White Storks from nests of low productivity pairs (i.e. with 1-2 fledglings) consumed a significantly (up to two-fold) higher biomass of Coleoptera, Orthoptera and all invertebrates, which also translated into a higher total biomass and a higher total energy content compared to the diet of high-productivity pairs (i.e. with 3-4 fledglings). Our data, in particular those relating to energy content in a variety of invertebrate taxa, and their body mass and functional division in terms of habitat preferences should be useful for other researchers to calculate energy budgets of predatory animals living in agricultural landscapes in Europe.

Relatedness of wildlife and livestock avian isolates of the nosocomial pathogen Acinetobacter baumannii to lineages spread in hospitals worldwide.

The natural habitats and potential reservoirs of the nosocomial pathogen Acinetobacter baumannii are poorly defined. Here, we put forth and tested the hypothesis of avian reservoirs of A. baumannii. We screened tracheal and rectal swab samples from livestock (chicken, geese) and wild birds (white stork nestlings) and isolated A. baumannii from 3% of sampled chicken (n = 220), 8% of geese (n = 40) and 25% of white stork nestlings (n = 661). Virulence of selected avian A. baumannii isolates was comparable to that of clinical isolates in the Galleria mellonella infection model. Whole genome sequencing revealed the close relationship of an antibiotic-susceptible chicken isolate from Germany with a multidrug-resistant human clinical isolate from China and additional linkages between livestock isolates and human clinical isolates related to international clonal lineages. Moreover, we identified stork isolates related to human clinical isolates from the United States. Multilocus sequence typing disclosed further kinship between avian and human isolates. Avian isolates do not form a distinct clade within the phylogeny of A. baumannii, instead they diverge into different lineages. Further, we provide evidence that A. baumannii is constantly present in the habitats occupied by storks. Collectively, our study suggests A. baumannii could be a zoonotic organism that may disseminate into livestock.

Corynebacterium pelargi sp. nov., isolated from the trachea of white stork nestlings.

A Gram-stain-positive, pleomorphic, oxidase-negative, non-motile isolate from the trachea of a white stork from Poland, designated strain 136/3(T), was subjected to a comprehensive taxonomic investigation. A comparative analysis of the 16S rRNA gene sequence showed highest similarities to Corynebacterium mustelae , Corynebacterium pseudotuberculosis , Corynebacterium vitaeruminis and Corynebacterium ulcerans (96.0-96.3%). The quinone system consisted of major amounts of MK-8(H2), minor amounts of MK-9(H2) and traces of MK-8 and MK-9. The polar lipid profile of strain 136/3(T) contained phosphatidylinositol and phosphatidylinositol-mannoside as major lipids and phosphatidylglycerol and an acidic glycolipid in moderate amounts. In addition small amounts of diphosphatidylglycerol, a phospholipid, an aminolipid and two lipids of unknown group affiliation were found. The polyamine pattern was composed of the major components spermidine and spermine. Putrescine, 1,3-diaminopropane, cadaverine, sym-homospermidine and tyramine were found in minor or trace amounts. The diamino acid of the peptidoglycan was meso-diaminopimelic acid. In the fatty acid profile straight-chain, saturated and mono-unsaturated fatty acids predominated (C(18 : 1)ω9c, C(16 : 1)ω7c, C16 : 0, C(18  : 0)). Corynemycolic acids were detected. Physiological traits as well as unique traits of the polar lipid profile and the fatty acid pattern distinguished strain 136/3(T) from the most closely related species. All these results indicate that strain 136/3(T) represents a novel species of the genus Corynebacterium for which we propose the name Corynebacterium pelargi sp. nov. The type strain is 136/3(T) ( =CIP 110778(T) =CCM 8517(T) =LMG 28174(T)).

Prevalence, virulence, and antimicrobial resistance of Campylobacter jejuni and Campylobacter coli in white stork Ciconia ciconia in Poland.

The aim of this study was to investigate the role of white stork Ciconia ciconia as a potential reservoir of Campylobacter spp. Antimicrobial resistance and the presence of putative virulence genes of the isolates were also examined. A total of 398 white stork chicks sampled in Western Poland in habitats with high density of breeding were examined. Rectal swabs were collected during breeding season 2009-2012 from storks developing in a relatively pure environment (Odra meadows), in polluted areas (a copper mining-smelting complex), and in suburbs. Of the anal swabs collected, 7.6% were positive for Campylobacter among chicks (5.3% samples positive for C. jejuni and 2.3% samples positive for C. coli). Samples from polluted areas had the highest prevalence of Campylobacter (12.2%). The prevalence of resistance among C. jejuni and C. coli isolates from young storks was as follows: to ciprofloxacin (52.4%, 44.4%), and to tetracycline (19%, 77.8%). All of the analyzed isolates were susceptible to macrolides. The resistance to both classes of antibiotics was found in the 23.3% of Campylobacter spp. All Campylobacter spp. isolates had cadF gene and flaA gene responsible for adherence and motility. CdtB gene associated with toxin production was present in 88.9% of C. coli isolates and 57.1% of C. jejuni isolates. The iam marker was found more often in C. coli strains (55.6%) compared to C. jejuni isolates (42.9%). Our results confirm the prevalence of Campylobacter spp. in the white stork in natural conditions and, because it lives in open farmlands with access to marshy wetlands, the environmental sources such as water reservoirs and soil-water can be contaminated from white stork feces and the pathogens can be widely disseminated. We can thus conclude that Campylobacter spp. may easily be transmitted to waterfowl, other birds, and humans via its environmental sources and/or by immediate contact.

The role of group I mGlu receptors in the expression of ethanol-induced conditioned place preference and ethanol withdrawal seizures in rats.

In animal models, N-methyl-D-aspartate (NMDA) receptors antagonists inhibit physical dependence and the reinforcing effects of ethanol. The group I metabotropic glutamate (mGlu) receptors antagonists (mGlu1 and mGlu5) attenuate excitatory effect of glutamate by functional modulation of the glutamate/NMDA receptors. The objective of the present study was to evaluate the effects of a selective mGlu5 receptors antagonist--MTEP, and mGlu1 receptors antagonist--EMQMCM, on two processes relevant to alcohol addiction: the expression of ethanol-induced conditioned place preference (CPP) paradigm, and ethanol withdrawal audiogenic seizures in rats. Our experiments indicated that EMQMCM at the doses of 5 and 10mg/kg, and MTEP at the doses of 2.5 and 5mg/kg, significantly attenuated the expression of ethanol CPP. Furthermore, both group I mGlu receptor antagonists, i.e. EMQMCM at the dose of 10mg/kg and MTEP at the dose of 5mg/kg, attenuated audiogenic seizures induced by the sound stimulus 12h after withdrawal of ethanol in dependent rats. Our study shows the importance of mGlu5 and mGlu1 receptors for the expression of ethanol-induced CPP and withdrawal seizures, although mGlu5 receptors antagonist (MTEP) was more potent than the antagonist of mGlu1 receptors (EMQMCM).

Pretreatment with group I metabotropic glutamate receptors antagonists attenuates lethality induced by acute cocaine overdose and expression of sensitization to hyperlocomotor effect of cocaine in mice.

Cocaine abuse and dependence is a worldwide health problem. However, there are no currently approved medications to reduce cocaine abuse/relapse and toxicity. The aim of the present study was to test, whether group I metabotropic glutamate receptors (mGluRs) antagonists (mGluR1 and mGluR5) differentially regulate toxic versus behavioral effects of cocaine, both phenomena relevant to the psychopathology of cocaine addiction in humans. In the present study, we assessed the impact of mGluR1 antagonist-EMQMCM and mGluR5 antagonist-MTEP on the cocaine-induced lethality and the expression of sensitization to hyperlocomotor effect of cocaine in mice. Our study indicated that EMQMCM and MTEP, both substances at the doses of 5 and 10 mg/kg (but not 2.5 mg/kg), decreased cocaine-induced lethality produced by 75 mg/kg of cocaine, which was given acutely. The effect of EMQMCM was dose-dependent, and this compound at the dose of 10 mg/kg almost completely abolished the lethality induced by cocaine. MTEP reduced this cocaine effect at the doses of 5 and 10 mg/kg, equally. Furthermore, EMQMCM (1.25-5 mg/kg) at the doses of 2.5 and 5.0 mg/kg, and MTEP (2.5-10 mg/kg) only at the highest dose of 10 mg/kg, significantly reduced the expression of cocaine-induced (10 mg/kg) behavioral sensitization. Our results suggest that stimulation of mGluR1 and mGluR5 is involved in lethal effect of cocaine overdose and cocaine seeking behavior evaluated in behavioral sensitization test. However, the participation of mGluR1 in these cocaine effects seems to be dominant. Therefore, antagonists showing preferences towards mGluR1 might be useful in therapy of cocaine toxicity and abuse.

Blood chemistry in white stork Ciconia ciconia chicks varies by sex and age.

Little is known on how blood biochemistry differs among avian chicks, especially in sexually monomorphic species. In this study we sampled blood chemistry of 342 white stork Ciconia ciconia chicks from nests in western Poland during four years (2005-2008). Special attention was paid to the effect of chick age and sex on blood biochemistry. Since white stork is a monomorphic species, the sex of chicks was established by a molecular technique. Nine blood biochemical parameters were studied: total protein concentration, urea, uric acid, triglycerides, total cholesterol, high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). There were sexual differences in total protein, uric acid, cholesterol, HDL and AST. However, total protein and uric acid only differed significantly between sexes if an age effect was included as a covariate in the analysis. Triglycerides decreased significantly, and AST, increased significantly with chick age. We confirm that blood biochemistry varies with chick age, but we also found significant differences between the sexes. Therefore, to understand changes in blood parameters, and to establish reference ranges useful in captive rearing of this endangered species, establishing gender may be important, even in very young individuals.

Dansyl-PQRamide, a putative antagonist of NPFF receptors, reduces anxiety-like behavior of ethanol withdrawal in a plus-maze test in rats.

Much evidence indicates that endogenous opioid peptides are involved in effects caused by ethanol. The aim of the present study was to determine whether dansyl-PQR amide, a putative antagonist of receptors for an anti-opioid peptide-neuropeptide FF (NPFF) could affect anxiety-like behavior measured during withdrawal from acute-, and chronic ethanol administration in the elevated plus maze test in rats. Our study indicated that intracerebroventricular (i.c.v.) administration of dansyl-PQRamide (2.4 and 4.8 nmol) reversed anxiety-like behavior measured as a percent time spent in the open arms, and a percent open arm entries onto the open arms in the elevated plus-maze test in rats. These effects were inhibited by NPFF (10 and/or 20 nmol, i.c.v.) in the experiments performed during withdrawal from acute- and chronic ethanol administration. During withdrawal from acute ethanol, naloxone (1mg/kg, i.p.), a nonselective opioid receptor antagonist, attenuated only an increased percent time spent in the open arms induced by dansyl-PQR amide (4.8 nmol). Dansyl-PQR amide, NPFF and naloxone given alone to naive rats did not have influence on spontaneous locomotor activity of animals. Furthermore, NPFF potentiated anxiety-like behavior during withdrawal from chronic, but not acute, ethanol administration in rats. Our data suggest that NPFF system is involved in regulation of affective symptoms of ethanol withdrawal. It seems that involvement of the NPFF system in ethanol withdrawal anxiety-like behavior is associated with regulation of the opioid system activity.

Enkephalin derivative, cyclo[Nepsilon,Nbeta-carbonyl-D-Lys2, Dap5] enkephalinamide (cUENK6), induces a highly potent antinociception in rats.

The aim of the study was to evaluate whether the newly synthesized analog of enkephalin, cyclo[N(epsilon),N(beta)-carbonyl-D-Lys(2), Dap(5)] enkephalinamide (cUENK6), a highly potent mu- (guinea pig ileum assay) and delta-receptors (mouse vas deferens assay) ligand, induces an antinociceptive effect in the hot-plate test and tail-immersion test after intracerebroventricular administration. Our study indicated that this peptide at the dose of 0.25 nmol produced comparable but at the dose of 0.5 nmol stronger than morphine (13 nmol), antinociceptive effect in both tests. Furthermore, rats with developed tolerance to morphine indicated cross-tolerance to antinociceptive effects of cUENK6. The antinociceptive effects of cUENK6 and morphine were inhibited by non-selective opioid receptor antagonist--naloxone. More detailed study indicated that the delta-opioid receptor antagonist - naltrindole very strongly and, to the lower extent, mu-opioid antagonist - beta-funaltrexamine (beta-FNA), inhibited antinociceptive effect of cUENK6 in the tail-immersion test. Nor-binaltorphimine (nor-BNI), a kappa-opioid receptor antagonist, did not influence this effect. These data suggest the dominant role of delta-opioid receptors as compared with mu-receptors in mediation antinociceptive effect of cUENK6. Furthermore, we found that cUENK6 is much more effective in inhibiting pain in the hot-plate (ED(50)=0.0792 nmol) than in the tail-immersion (ED(50)=0.3526 nmol) test. However, cUENK6 at the antinociceptive doses induced hypolocomotion, and although this effect is observed after administration of opioid agonists in rats as a one phase of their biphasic action (inhibition followed by activation), in our study it was not naloxone-reversible. Therefore, our study suggests that not only opioid receptors may be involved in behavioral effects of cUENK6.

The influence of various glutamate receptors antagonists on anxiety-like effect of ethanol withdrawal in a plus-maze test in rats.

The aim of the present study was to determine whether various glutamate receptor antagonists could affect ethanol withdrawal-induced anxiety-like behavior measured in the elevated plus-maze test in rats. In our study, memantine (8 and 12 mg/kg), a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, did not show any effect on ethanol withdrawal anxiety. Acamprosate (NMDA and metabotropic glutamate5 (mGlu5) receptor antagonist), at a dose of 400 mg/kg showed anxiolytic-like effect, thus increasing the percent of time spent in open arms and open arms entries. Antagonists of group I mGlu receptors, such as MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine, mGlu5 receptor) or EMQMCM (3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)-methanone methanesulfonate, mGlu1 receptor), caused similar effects to acamprosate. In contrast to acamprosate and MTEP, EMQMCM (5 mg/kg) elevated the ethanol withdrawal-induced decrease in locomotion. When given alone to the saline-treated group, EMQMCM indicated anxiolytic-like effect. Our results imply a crucial role of mGlu5 receptor in an anxiety-like effect of ethanol withdrawal because MTEP (a selective mGlu5 receptor antagonist) and acamprosate (which also indirectly inhibits mGlu5 receptor) attenuated ethanol withdrawal anxiety-like behavior without influence on ethanol withdrawal hypolocomotion and did not show any effect in the saline-treated groups. However, difference in anxiolytic-like potency between both these group I mGlu receptors antagonists may be due to the recent experimental design. Therefore, taking into account a positive correlation between ethanol withdrawal-induced anxiety and relapse to ethanol drinking, our results suggest that mGlu receptor antagonists of group I (similarly to acamprosate) could prevent relapse to drinking and, therefore they might be useful in therapy of alcoholism.

Comparison of the effects of mGluR1 and mGluR5 antagonists on the expression of behavioral sensitization to the locomotor effect of morphine and the morphine withdrawal jumping in mice.

The aim of the present study was to compare the influence of group I metabotropic glutamate receptor (mGluR) antagonists (mGluR1 and mGluR5) on the expression of sensitization to the locomotor effect of morphine. We also tested how these compounds affect the morphine withdrawal jumps in mice. In our study, the mGluR1 antagonist EMQMCM [3-ethyl-2-methyl-quinolin-6-yl-(4-methoxy-cyclohexyl)-methanone methanesulfonate] and the mGluR5 antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl) ethynyl] pyridine) were used. Sensitization was induced by five intraperitoneal (i.p.) injections of morphine at the dose of 10 mg/kg, every 3 days. Morphine dependence was induced by subcutaneous (s.c.) implantation of pellets containing 37.5 mg of morphine base for three days. Our data indicate that pretreatment with EMQMCM (5, 10, 20 mg/kg) and MTEP (5, 10 mg/kg) on the challenge day, inhibited the expression of sensitization to the locomotor effect of morphine in mice. Antagonists of both subtypes of the group I mGlurs given alone, did not modify the acute locomotor effect of morphine. On the other hand, EMQMCM did not attenuate the morphine withdrawal jumps precipitated by naloxone (4 mg/kg). The results suggest that both subtypes of the group I mGluRs (mGluR1 and mGluR5) take part in the expression of morphine sensitization processes but mGluR1 is not involved in the expression of morphine withdrawal jumps in mice. These findings may have implications for the treatment of opiate addiction in future.

N-methyl-D-aspartate and group I metabotropic glutamate receptors are involved in the expression of ethanol-induced sensitization in mice.

Effects of acamprosate and ionotropic uncompetitive N-methyl-D-aspartate receptor antagonists and group I metabotropic glutamatergic receptor antagonists on the expression of ethanol-induced sensitization were investigated in mice. The results indicated that acamprosate (200 and 400 mg/kg) and N-methyl-D-aspartate receptor antagonists, neramexane (10 and 20 mg/kg) and MK-801 (0.1 and 0.2 mg/kg), inhibited the expression of ethanol-induced sensitization. Acamprosate, but not the other compounds tested, also blocked the stimulant effect of acute injections of ethanol. Among the group I metabotropic glutamatergic receptor antagonists, only the metabotropic glutamatergic receptor 5 antagonist, MTEP (5, 10, and 20 mg/kg) showed an effect similar to the N-methyl-D-aspartate receptor antagonists. The metabotropic glutamatergic receptor 1 antagonist, EMQMCM (5, 10, and 20 mg/kg), however, potentiated the inhibitory effect of MK-801 on the expression of ethanol-induced sensitization. The findings indicate that glutamatergic neurotransmission is important in the ethanol-induced sensitization process, and suggest that co-administration of metabotropic glutamatergic receptor 1 antagonists and N-methyl-D-aspartate receptor antagonists may be useful in therapy for alcoholism.

Effect of neramexane on ethanol dependence and reinforcement.

It has been suggested that drugs modulating the glutamate/N-methyl-D-aspartate (NMDA) receptor system may be useful in the treatment of alcohol dependence. The effect of neramexane, a low-to-moderate affinity uncompetitive NMDA receptor antagonist, was examined on the development and expression of ethanol dependence (withdrawal-associated audiogenic seizures) and ethanol-induced conditioned place preference. Neramexane hydrochloride (3.5 mg/kg and higher) inhibited both the development and expression of ethanol dependence. Neramexane hydrochloride also inhibited the acquisition (1.75 mg/kg and higher) and expression (3.5 mg/kg and higher) of ethanol-induced place preference. Our data support therapeutic potential of neramexane as a treatment for alcohol abuse.