Saline Animals Research Articles

Neuropharmacological effects of lipoic acid and ubiquinone on δ‐aminolevulinic dehydratase, Na+, K+‐ATPase, and Mg2+‐ATPase activities in rat hippocampus after pilocarpine‐induced seizures

In this study, we investigated the effects of lipoic acid (LA) in the hippocampus oxidative stress caused by pilocarpine-induced seizures in adult rats. Wistar rats were treated with 0.9% saline (i.p., control group), LA (10mg/kg, i.p., LA group), ubiquinone [20mg/kg, i.p., ubiquinone (UQ) group], pilocarpine (400mg/kg, i.p., P400 group), and the association of LA (10mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.) or UQ (20mg/kg, i.p.) plus pilocarpine (400mg/kg, i.p.), 30min before of administration of P400 (LA plus P400 group and UQ plus P400 group, respectively). After the treatments, all groups were observed for 1h. The enzyme activities (δ-aminolevulinic dehydratase (δ-ALA-D), Mg(2+) -ATPase, and Na(+) , K(+) -ATPase) were measured using spectrophotometric methods, and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA and UQ were also evaluated on the same parameters. We reported here for the first time that Na(+) , K(+) -ATPase and δ-ALA-D activities inhibition and Mg(2+) -ATPase stimulation in the pilocarpine model are probably attributed to the oxidative stress caused by seizures in the rat hippocampus. The addition of the antioxidants LA and UQ may reverses the previously mentioned Na(+) , K(+) -ATPase and δ-ALA-D inhibitions and Mg(2+) -ATPase stimulation. The oxidative stress plays an important signaling role in pilocarpine-induced seizures, and antioxidant drugs might be considered as therapeutical tools in this pathology.

Chronic Intermittent Ethanol Exposure in Early Adolescent and Adult Male Rats: Effects on Tolerance, Social Behavior, and Ethanol Intake

Given the prevalence of alcohol use in adolescence, it is important to understand the consequences of chronic ethanol exposure during this critical period in development. The purpose of this study was to assess possible age-related differences in susceptibility to tolerance development to ethanol-induced sedation and withdrawal-related anxiety, as well as voluntary ethanol intake after chronic exposure to relatively high doses of ethanol during adolescence or adulthood. Juvenile/adolescent and adult male Sprague-Dawley rats were assigned to one of five 10-day exposure conditions: chronic ethanol (4 g/kg every 48 hours), chronic saline (equivalent volume every 24 hours), chronic saline/acutely challenged with ethanol (4 g/kg on day 10), nonmanipulated/acutely challenged with ethanol (4 g/kg on day 10), or nonmanipulated. For assessment of tolerance development, duration of the loss of righting reflex (LORR) and blood ethanol concentrations (BECs) upon regaining of righting reflex (RORR) were tested on the first and last ethanol exposure days in the chronic ethanol group, with both saline and nonmanipulated animals likewise challenged on the last exposure day. Withdrawal-induced anxiety was indexed in a social interaction test 24 hours after the last ethanol exposure, with ethanol-naïve chronic saline and nonmanipulated animals serving as controls. Voluntary intake was assessed 48 hours after the chronic exposure period in chronic ethanol, chronic saline and nonmanipulated animals using an 8-day 2 bottle choice, limited-access ethanol intake procedure. In general, adolescent animals showed shorter durations of LORR and higher BECs upon RORR than adults on the first and last ethanol exposure days, regardless of chronic exposure condition. Adults, but not adolescents, developed chronic tolerance to the sedative effects of ethanol, tolerance that appeared to be metabolic in nature. Social deficits were observed after chronic ethanol in both adolescents and adults. Adolescents drank significantly more ethanol than adults on a gram per kilogram basis, with intake uninfluenced by prior ethanol exposure at both ages. Adolescents and adults may differ in their ability and/or propensity to adapt to chronic ethanol exposure, with adults, but not adolescents, developing chronic metabolic tolerance. However, this chronic exposure regimen was sufficient to disrupt baseline levels of social behavior at both ages. Taken together, these results suggest that, despite the age-related differences in tolerance development, adolescents are as susceptible as adults to consequences of chronic ethanol exposure, particularly in terms of disruptions in social behavior. Whether these effects would last into adulthood remains to be determined.

Integrating livestock production with crops and saline fish ponds to reduce greenhouse gas emissions

Extensive grazing systems in the tropics have large greenhouse gas (GHG) emissions. Here an integrated cropping, livestock farming and saline pond aquaculture system is described which also reduces GHG emissions in tropical farming. The system was developed in the 1980s in the central Philippines and is re-evaluated in terms of its potential to reduce emissions from livestock production, particularly in wet and wet-dry tropical regions. The estimated cumulative annual GHG emission savings amount to 12.9 tonne CO2-e per head of cattle exiting the integrated feedlot system after 300 days. Use of silage from crop by-products and implementation of a feed-lot programme enabled immediate and significant reductions of GHG emissions over extensive cattle grazing. Integration with a saline animal waste processing pond allowed production of natural feed products, cyanobacteria algal mat for use in aquaculture, as crop fertiliser and soil amendment or in the silage manufacture process. Fish production from ponds receiving the harvested algal mat resulted in an annual average of 3300 kg/ha compared to an average 700 kg/ha in inorganic fertilised ponds. The unitised ratios for the integrated system were respectively: 1 ha sugarcane: 4 head of cattle: 0.13 ha saline waste processing pond. Stoichiometrically, bio-processing of waste material in saline ponds provides a novel solution to GHG emissions from feedlots. It uses a multi-step process dominated by cyanobacteria mats in which all the captured liquid and solid waste is passed through fermentation and a mixed aerobic and anaerobic photosynthesis/photosynthesis and mixed aerobic/anaerobic sulphate reduction pathway to use organic wastes and also reduce GHG emissions. Sulphate is reduced and sequestered as iron sulphide eliminating the potential for harmful sulphide emissions. Calcium carbonate precipitation in the cyanobacteria mats results in significant sequestration of carbon. The process produces organic feed matter with a three-fold increase in nitrogen levels arising from nitrogen fixation in the treatment pond.

Dipyridamole Treatment Prior to Stroke Onset: Examining Post-stroke Cerebral Circulation and Outcome in Rabbits

Clinical observations have indicated that secondary treatment with dipyridamole (DIP) may ameliorate stroke severity. The purpose of this study was to explore the effect of pre-stroke DIP treatment on stroke outcome in a rabbit model of embolic occlusion. Twenty male New Zealand white rabbits were randomly selected for intravenous treatment with DIP (n = 10) or saline (n = 10) for 7days prior to an embolic cerebral occlusion by an autologous blood clot. Multiple computed tomography perfusion scans were acquired out to 28days post-stroke to map cerebrohemodynamics, in conjunction with neurological assessments and histopathology. The DIP-treated group fared better than the saline group on several accounts: 66% of them survived to 28days, whilst saline animals all had to be euthanized by day7 due to severe neurological deficits. They presented with significantly more viable tissue in the ischemic hemisphere as well as fewer neurological deficits on days4 and 7. Furthermore, DIP-treated animals exhibited improved cerebrohemodynamics by 24h and had less incidence of haemorrhage within their infarcted regions (p < 0.05). DIP treatment prior to stroke onset can significantly improve neurological outcome, cerebral hemodynamics, and final infarct volume.

Deficits of Hypothalamic GLUT2 Immunolabeling After Streptozotocin Microinjection into the Ventromedial Hypothalamic Nucleus of the Rat

Event Abstract Back to Event Deficits of Hypothalamic GLUT2 Immunolabeling After Streptozotocin Microinjection into the Ventromedial Hypothalamic Nucleus of the Rat I. Telkes1*, C. Szalay1, L. Lénárd1, 2 and Z. Karádi2 1 University of Pécs, Institute of Physiology, Medical School, Hungary 2 University of Pécs and Neurophysiology Research Group of the Hungarian Academy of Sciences (HAS), Institute of Physiology, Medical School, Hungary Glucose monitoring (GM) neurons of the hypothalamus are important in the regulation of feeding and metabolism. We have shown recently that streptozotocin (STZ) administration into the ventromedial hypothalamus (VMH) elicits selective destruction of specific GM neurons causing severe deficits of feeding and metabolism. STZ is selectively toxic to cells expressing the type-2 glucose transport protein GLUT2. This transporter was first found in pancreatic b-cells, and it is mainly localized to GM neurons in the brain. In the present study, we were interested whether STZ microinjections into the VMH cause loss of hypothalamic GLUT2 immunolabeling in the rat. Young adult male rats (n=3) were bilaterally microinjected with 0.75 µl 0,0037 M STZ into the VMH. Rats injected with physiological saline and untreated animals served as controls (n=4). Histological sections of brain and pancreas were immunolabeled with GLUT2-specific antibodies after 48h survival. We found a massively reduced GLUT2 immunolabeling in the periventricular hypothalamic nuclei in brains of STZ-microinjected animals without any difference in immunopositivity of pancreatic β-cells against controls. Our preliminary results suggest that the metabolic and behavioral changes following hypothalamic STZ injections can be explained by a selective destruction of GLUT2-expressing neurons of the GM network. Acknowledgements Supported by: OTKA K 68431, Ajinomoto 51064/2009, and HAS Keywords: Molecular and cellular neurobiology, Neuroscience Conference: 13th Conference of the Hungarian Neuroscience Society (MITT), Budapest, Hungary, 20 Jan - 22 Jan, 2011. Presentation Type: Abstract Topic: Molecular and cellular neurobiology Citation: Telkes I, Szalay C, Lénárd L and Karádi Z (2011). Deficits of Hypothalamic GLUT2 Immunolabeling After Streptozotocin Microinjection into the Ventromedial Hypothalamic Nucleus of the Rat. Front. Neurosci. Conference Abstract: 13th Conference of the Hungarian Neuroscience Society (MITT). doi: 10.3389/conf.fnins.2011.84.00055 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 03 Mar 2011; Published Online: 23 Mar 2011. * Correspondence: Dr. I. Telkes, University of Pécs, Institute of Physiology, Medical School, Pécs, Hungary, ildiko.telkes@aok.pte.hu Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers I. Telkes C. Szalay L. Lénárd Z. Karádi Google I. Telkes C. Szalay L. Lénárd Z. Karádi Google Scholar I. Telkes C. Szalay L. Lénárd Z. Karádi PubMed I. Telkes C. Szalay L. Lénárd Z. Karádi Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Novel Approach to Early Detection of Doxorubicin Cardiotoxicity by Gadolinium-Enhanced Cardiovascular Magnetic Resonance Imaging in an Experimental Model

We sought to determine whether cardiovascular magnetic resonance measures of gadolinium (Gd) signal intensity (SI) within the left ventricular myocardium are associated with future changes in left ventricular ejection fraction (LVEF) after receipt of doxorubicin (DOX). Forty Sprague-Dawley rats were divided into 3 groups scheduled to receive weekly intravenous doses of normal saline (n = 7), 1.5 mg/kg DOX (n = 19), or 2.5 mg/kg DOX (n = 14). Magnetic resonance determinations of LVEF and myocardial Gd-SI were performed before and at 2, 4, 7, and 10 weeks after DOX initiation. During treatment, animals were euthanized at different time points so that histopathologic assessments of the left ventricular myocardium could be obtained. Within-group analyses were performed to examine time-dependent relations between Gd-SI and primary events (deterioration in LVEF or an unanticipated death). Six of 19 animals receiving 1.5 mg/kg DOX and 10 of 14 animals receiving 2.5 mg/kg DOX experienced a primary event; no normal saline animals experienced a primary event. In animals with a primary event, histopathologic evidence of myocellular vacuolization occurred (P = 0.04), and the Gd-SI was elevated relative to baseline at the time of the event (P < 0.0001) and during the measurement period before the event (P = 0.0001). In all animals (including normal saline) without an event, measures of Gd-SI did not differ from baseline. After DOX, low serial measures of Gd-SI predict an absence of an LVEF drop or unanticipated death. An increase in Gd-SI after DOX forecasts a subsequent drop in LVEF as well as histopathologic evidence of intracellular vacuolization consistent with DOX cardiotoxicity.

섬유근통 동물 모델에서 포도씨 추출 proanthocyanidin의 진통 효과

산성 식염수 쥐모델은 사람의 섬유근통에 근접한 모델로 제시되고 있다. 포도씨에서 얻은 oligomeric proanthocyanidin complexes (OPC)는 항산화제로 알려져 있다. 저자들은 산성 식염수 모델에서 통증 역치에 대한 OPC의 효과를 연구했다. 좌측 장딴지 근육에 pH 4.0의 산성 식염수 <TEX>$100\;{\mu}l$</TEX>를 0일과 5일에 주사했다. 대조군은 pH 7.2의 생리 식염수를 같은 스케줄로 주사했다. 산성 식염수 그룹 10마리를 다시 두 그룹으로 나누어 한 그룹은 멸균 식염수, 다른 한 그룹은 OPC 300 mg/kg를 복강 내 주사했다. 복강 내 주사 한시간 후 다시 통각에 대한 역치를 조사했다. 0일에 비해 7일에서 산성 식염수 모델은 기계적 과통각을 나타냈다(p<0.05). OPC 300 mg/kg를 복강내 주사한 그룹에서 강력한 항통각 효과를 나타냈다(주사측 발바닥, p=0.001; 반대측 발바닥, p=0.002). 면역조직화학 염색상 복강내 식염수를 처치한 대조군에 비해 OPC 처치군에서 대뇌의 M1 및 M2 영역에서 산-감지 이온 통로3의 발현이 감소되었다(p<0.05). 사람의 섬유근통에서 OPC 치료의 효과를 보기 위한 연구가 향후 필요할 것으로 생각된다. The acidic saline animal model of pain has been suggested to mimic fibromyalgia (FM). Oligomeric proanthocyanidin complexes (OPC) from grape seeds are known to act as an antioxidant. We studied the effects of OPC on the pain threshold in the acidic saline animal model of pain. The left gastrocnemius muscle was injected with <TEX>$100\;{\mu}l$</TEX> of saline at pH 4.0 under brief isoflurane anesthesia on days 0 and 5. Control rats (n=5) received identical injections of physiological saline (pH 7.2) on the same schedule. Rats (n=10) with acidic saline injection were separated into two study subgroups. After measurement of pre-drug pain thresholds, rats were injected intraperitoneally with either saline or OPC 300 mg/kg. Paw withdrawal thresholds to pressure were again measured 60 min after intraperitoneal injection. Nociceptive thresholds were measured with a Dynamic Plantar Aesthesiometer by applying an increasing pressure to right or left hind paw until the rat withdrew the paw. Compared to baseline (day 0), acid injections produced mechanical hyper-responsiveness on day 7 (pre-drug) in these rats [p<0.05]. A potent antihyperalgesic effect was observed when rats were injected intraperitoneally with OPC 300 mg/kg [injected paw, p=0.001; contralateral paw, p=0.002]. OPC treatment decreased the expression of acid sensing ion channel 3 in the brain motor cortex area on immunohistochemical staining when OPC 300 mg/kg was administered intraperitoneally in the animal model of FM pain [p<0.05]. Further research is required to determine the efficacy of OPC treatments in FM pain in humans.

Abstract 1408: Nicotine decreases the therapeutic efficacy of radiotherapy and chemoradiotherapy in vivo

Abstract Background: Continued tobacco use during cancer treatment has been associated with poor outcome. Nicotine replacement is currently used as a standard of care for smoking cessation in cancer patients; however, prior data demonstrates that nicotine can promote tumor growth and decrease the effectiveness of cancer treatment in vitro. Methods: Athymic nude mice with human H460 lung cancer cell xenografts were stratified into three Groups beginning when tumors reached 5 mm in maximal dimension: control (CON), short term nicotine (STN, 60 ug subcutaneously every other day x 6 days), or long term nicotine (LTN, 60 ug SC every other day until tumor endpoint). Within each Group, mice were further stratified into three Treatments consisting of saline (SAL), radiotherapy (RT, 3 Gy daily x 5 days), or chemoradiotherapy (CRT, RT + concurrent cisplatin intraperitoneally 3 mg/kg daily x 5 days). Tumor volumes were measured and compared between Treatments and Groups (n=10 per Treatment within each Group). This protocol was approved by the Institutional Animal Care and Use Committee at the University of Kentucky. Results: In CON animals, RT (199 uL at day 30) or CRT (100 uL at day 30) significantly prevented tumor regrowth as compared with control SAL animals (864 uL at day 10 requiring euthanasia as per protocol). As expected, CRT was more effective than RT (p&amp;lt;0.05). Nicotine administration alone (STN or LTN) had no effect on tumor growth rate as compared with CON. In contrast, administration of LTN significantly increased tumor regrowth in RT animals (356 uL at day 30, p&amp;lt;0.05) and CRT treated animals (170 uL ad day 30, p&amp;lt;0.05). To eliminate the effects of nicotine on proliferation following completion of RT or CRT, animals were treated with STN. Administration of STN also significantly increased tumor regrowth in RT animals (328 uL at day 30, p&amp;lt;0.05) and CRT animals (176 uL at day 30, p&amp;lt;0.05) with virtually identical regrowth curves as demonstrated for LTN animals. Conclusions: Results demonstrate that nicotine significantly reduces the efficacy of RT and CRT in vivo. Moreover, data suggest that nicotine use during treatment is the primary determinant of decreased therapeutic response. These results may significantly alter current recommendations for smoking cessation in cancer treatment populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1408.

Acute respiratory toxicity following inhalation exposure to soman in guinea pigs

Respiratory toxicity and lung injury following inhalation exposure to chemical warfare nerve agent soman was examined in guinea pigs without therapeutics to improve survival. A microinstillation inhalation exposure technique that aerosolizes the agent in the trachea was used to administer soman to anesthetized age and weight matched male guinea pigs. Animals were exposed to 280, 561, 841, and 1121 mg/m 3 concentrations of soman for 4 min. Survival data showed that all saline controls and animals exposed to 280 and 561 mg/m 3 soman survived, while animals exposed to 841, and 1121 mg/m 3 resulted in 38% and 13% survival, respectively. The microinstillation inhalation exposure LCt 50 for soman determined by probit analysis was 827.2 mg/m 3. A majority of the animals that died at 1121 mg/m 3 developed seizures and died within 15–30 min post-exposure. There was a dose-dependent decrease in pulse rate and blood oxygen saturation of animals exposed to soman at 5–6.5 min post-exposure. Body weight loss increased with the dose of soman exposure. Bronchoalveolar lavage (BAL) fluid and blood acetylcholinesterase and butyrylcholinesterase activity was inhibited dose-dependently in soman treated groups at 24 h. BAL cells showed a dose-dependent increase in cell death and total cell counts following soman exposure. Edema by wet/dry weight ratio of the accessory lung lobe and trachea was increased slightly in soman exposed animals. An increase in total bronchoalveolar lavage fluid protein was observed in soman exposed animals at all doses. Differential cell counts of BAL and blood showed an increase in total lymphocyte counts and percentage of neutrophils. These results indicate that microinstillation inhalation exposure to soman causes respiratory toxicity and acute lung injury in guinea pigs.

Effects of reversible inactivation of the medial septum on rat exploratory behavior in the elevated plus-maze using a test–retest paradigm

The effect of intraseptal injections of lidocaine before a first or a second session in the elevated plus-maze, in a test–retest paradigm, was investigated. In addition to gross session analyses, a minute-by-minute analysis of the sessions was used to evaluate both anxiety and memory. Lidocaine injections before the test session produced increases in the frequency of entries, time spent and distance run in the open arms without affecting activity occurring in the closed arms. During the retest session, saline- and lidocaine-treated rats exhibited increased indices of anxiety and lidocaine-treated rats exhibited decreased closed-arm entries. The minute-by-minute analysis showed a faster decrease in anxiety-related behaviors during the test session by saline- than by lidocaine-treated rats and a significant decrease in closed-arm exploration by saline-treated rats, but not by lidocaine-treated ones. Lidocaine injection before the retest session produced increases in the frequency of entries, time spent and distance run in the open arms in the second session when compared with saline-treated rats. Minute-by-minute analysis showed an increase in the time spent in the open arms by lidocaine animals at the beginning of the retest session in comparison to saline animals and a significant decrease in closed-arm exploration by both groups. These results suggest that inactivation of the medial septum by lidocaine affects the expression of unconditioned and conditioned forms of anxiety in the elevated plus-maze and, in a lesser way, the acquisition and retention of spatial information.

Long-term Physiologically Regulated Expression of the Low-density Lipoprotein Receptor In Vivo Using Genomic DNA Mini-gene Constructs

Familial hypercholesterolemia (FH) is a condition caused by mutations in the low-density lipoprotein receptor (LDLR) gene. Expression of LDLR is highly regulated and excess receptor expression is cytotoxic. To incorporate essential gene regulation into a gene therapy vector for FH, we generated vectors in which the expression of therapeutic human LDLR gene, or luciferase reporter gene, is driven by 10 kb of human LDLR genomic DNA encompassing the promoter region including elements essential for physiologically regulated expression. Using luciferase expression and specific LDL binding and internalization assays, we have shown in vitro that the genomic promoter element confers long-term, physiologically regulated gene expression and complementation of receptor deficiency in culture for 240 cell-generations. This was demonstrated in the presence of sterols or statins, modifiers of LDLR promoter activity. In vivo, we demonstrate efficient liver-specific delivery and expression of luciferase following hydrodynamic tail-vein injection and confirm that expression from the LDLR promoter element is sensitive to statin administration. We also demonstrate long-term LDLR expression from the 10-kb promoter element up to 9 months following delivery. The vector system that we describe provides the efficient delivery, long-term expression, and physiological regulation required for a successful gene therapy intervention for FH.

Lipoic acid blocks seizures induced by pilocarpine via increases in δ-aminolevulinic dehydratase and Na +, K +-ATPase activity in rat brain

In the present study we investigated the effects of lipoic acid (LA) on δ-aminolevulinic dehydratase (δ-ALA-D) and Na +, K +-ATPase activities in rat brain after seizures induction by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (10 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), or the combination of LA (10 mg/kg, i.p.) with pilocarpine (400 mg/kg, i.p.), 30 min before administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 1 h. The enzyme activities (δ-ALA-D and Na +, K +-ATPase) were measured using spectrophotometric methods, and the results were compared with that obtained from saline and pilocarpine-treated animals. Neuroprotective effects of LA against seizures were evaluated based on those enzyme activities. The pilocarpine group showed a reduction in δ-ALA-D and Na +, K +-ATPase activities after seizures. In turn, LA plus pilocarpine abolished the appearance of seizures and reversed the decreased in δ-ALA-D and Na +, K +-ATPase activities produced by seizures, when compared to the pilocarpine seizing group. The results from the present study demonstrate that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by increasing δ-ALA-D and Na +, K +-ATPase activities in rat brain during seizures.

Glycine Receptors in the Nucleus Accumbens Involved in the Ethanol Intake‐Reducing Effect of Acamprosate

We have previously demonstrated that strychnine-sensitive glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area are involved in mediating ethanol (EtOH)-induced elevation of dopamine in the rat mesolimbic dopamine system. This neuronal circuitry was also demonstrated to mediate dopamine elevation in the nAc after both taurine, an endogenous agonist of GlyRs, and acamprosate, a synthetic derivate of homotaurine. The aim of this study was to investigate whether the EtOH intake-reducing effect of acamprosate involves accumbal GlyRs. For this purpose, we used a voluntary EtOH consumption model where EtOH medium- and high-preferring rats were implanted with guide cannulae in the nAc. The animals received daily injections of acamprosate or 0.9% NaCl before accessing a bottle of 6% EtOH and a bottle of water. After 2 days, a microinjection of strychnine or vehicle preceded the daily systemic injection and bottle-access period. Acamprosate, but not saline, decreased EtOH intake. Pretreatment with Ringer in the nAc did not influence EtOH intake in saline or acamprosate-treated animals. Pretreatment with strychnine had no effect on EtOH intake in saline-treated animals, whereas it completely reversed the EtOH intake-reducing effect of acamprosate. Based on current and previous results, we suggest that acamprosate primarily interacts with accumbal GlyRs and secondarily with ventral tegmental nAChRs, in a similar manner to that previously observed with EtOH and taurine. The interaction between acamprosate and GlyRs does not only influence dopamine output in the nAc but also EtOH consumption, giving further support for our hypothesis that GlyRs are of importance in EtOH reinforcement.

Pilocarpine-induced seizures produce alterations on choline acetyltransferase and acetylcholinesterase activities and deficit memory in rats.

In the present study, we investigated the effect of seizures on rat performance in the Morris water maze task, as well as on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in rat hippocampus. Wistar rats were treated with 0.9% saline (i.p., control group) and pilocarpine (400 mg/kg, i.p., pilocarpine group). After the treatments all groups were observed for 1 h. The changes on reference and working spatial memory caused by pilocarpine administration were observed in seized rats. The ChAT and AChE activities were measured using spectrophotometric methods and the results compared to values obtained from saline animals. Its activities were also determined after behavioral task. Results showed that seizures alter reference memory when compared to saline-treated animals. In the working memory task, we observed a significant day's effect with significant differences between control and pilocarpine-induced seizures. In pilocarpine group, it was observed a significant decreased in ChAT and AChE activities, when compared to control group. Our findings suggest that seizures caused cognitive dysfunction and a decrease of ChAT and AChE activities that might be related, at least in part, to the neurological problems presented by seizures induced by pilocarpine.

Lipoic acid alters delta-aminolevulinic dehydratase, glutathione peroxidase and Na+,K+-ATPase activities and glutathione-reduced levels in rat hippocampus after pilocarpine-induced seizures.

In the present study, we investigated the effects of lipoic acid (LA) in the brain oxidative stress caused by pilocarpine-induced seizures in adult rats. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (10 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of LA (10 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before the administration of LA (LA plus pilocarpine group). After the treatments, all groups were observed for 1 h. The enzyme activities [delta-aminolevulinic dehydratase (delta-ALA-D), glutathione peroxidase (GPx), glutathione reductase (GR), and Na+,K+-ATPase] as well as the glutathione-reduced (GSH) and ascorbic acid (AA) concentrations were measured using spectrophotometric methods, and the results were compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA were also evaluated on the same parameters. In pilocarpine group, no changes were observed in GPx and GR activities and AA content. Moreover, in the same group, decrease in GSH levels as well as a reduction in delta-ALA-D and Na+,K+-ATPase activities after seizures was observed. In turn, in LA plus pilocarpine group, the appearance of seizures was abolished, and the decreases in delta-ALA-D and Na+,K+-ATPase activities produced by seizures as well as increases in GSH levels and GPx activity were reversed, when compared to the pilocarpine seizing group. The results of the present study demonstrated that preadministration of LA abolished seizure episodes induced by pilocarpine in rat, probably by reducing oxidative stress in rat hippocampus caused by seizures.

Effects of lipoic acid on oxidative stress in rat striatum after pilocarpine-induced seizures

The relationship between free radical and scavenger enzymes has been found in the epilepsy and reactive oxygen species have been implicated in seizure-induced neurodegeneration. It has been suggested that pilocarpine-induced seizures is mediated by increases in oxidative stress. Current researches have suggested that antioxidant compounds may afford some level of neuroprotection against the neurotoxicity of seizures in cellular level. The objective of the present study was to evaluate the neuroprotective effects of lipoic acid (LA) in rats, against the observed oxidative stress during seizures induced by pilocarpine. Wistar rats were treated with 0.9% saline (i.p., control group), LA (20 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., P400 group), and the association of LA (20 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of LA (LA plus P400 group). After the treatments all groups were observed for 1 h. The enzyme activities as well as the lipid peroxidation and nitrite concentrations were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Protective effects of LA were also evaluated on the same parameters. In P400 group there was a significant increase in lipid peroxidation, nitrite level and glutathione peroxidase (GPx) activity. However, no alteration was observed in superoxide dismutase (SOD) and catalase activities. Antioxidant treatment significantly reduced the lipid peroxidation level and nitrite content as well as increased the SOD, catalase and GPx activities in rat striatum after seizures. Our findings strongly support the hypothesis that oxidative stress in striatum occurs during seizures induced by pilocarpine, proving that brain damage induced by the oxidative process plays a crucial role in seizures pathogenic consequences, and also imply that strong protective effect could be achieved using LA.

Lipoic Acid Increases Hippocampal Choline Acetyltransferase and Acetylcholinesterase Activities and Improvement Memory in Epileptic Rats

In the present study we investigated the effect of seizures on rat performance in the Morris water maze task, as well as on choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activities in rat hippocampus. Wistar rats were treated with 0.9% saline (i.p., control group), lipoic acid (20 mg/kg, i.p., LA group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of LA (20 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min before of administration of LA (LA plus pilocarpine group). After the treatments all groups were observed for 1 h. The effect of lipoic acid administration was observed on reference and working spatial memory of seized rats. The ChAT and AChE activities were measured using spectrophotometric methods and the results compared to values obtained from saline and pilocarpine-treated animals. Its activity was also determined after behavioral task. Results showed that pretreatment with lipoic acid did not alter reference memory when compared to saline-treated animals. In the working memory task, we observed a significant day's effect with significant differences between control and pilocarpine-induced seizures and pretreated animals with lipoic acid. In LA plus pilocarpine group was observed a significantly increased in ChAT and AChE activities, when compared to pilocarpine group. Results showed that acute administration of lipoic acid alone did not alter hippocampal ChAT and AChE activities. Our findings suggest that seizures caused cognitive dysfunction and a decrease of ChAT and AChE activities that might be related, at least in part, to the neurological problems presented by epileptic patients. Lipoic acid can reverse cognitive dysfunction observed in seized rats as well as increase the ChAT and AChE activities in hippocampus of rats prior to pilocarpine-induced seizures, suggesting that this antioxidant could be used in clinic treatment of epilepsy.

Naloxone facilitates appetitive extinction and eliminates escape from frustration

Two experiments tested the effects of opioid receptor blockage on behavior. In Experiment 1, rats reinforced for lever pressing with either sucrose or food pellets received treatment with saline, 2, and 10 mg/kg naloxone, i.p. (within-subject design). Naloxone 10 mg/kg increased response latency, but 2 mg/kg had no effect. When shifted to extinction (between-group design), naloxone (2 and 10 mg/kg) facilitated extinction relative to saline animals, after reinforcement with either sucrose or food pellets. In Experiment 2, after 10 sessions of access to 32% sucrose or an empty tube (between-group design), all rats were exposed to the empty tube while allowing them to jump over a barrier into a different compartment. Escape latencies were shorter for downshifted saline than for saline rats always given access to the empty tube. This escape-from-frustration effect was eliminated by naloxone (2 mg/kg, i.p.). Opioid blockage appears to reduce the value of alternative incentives.

Efectos de la Inyección Intrahipocampal de Escopolamina sobre el Comportamiento en el Laberinto en Cruz Elevado

Normal 0 MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:Table Normal; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:Times New Roman;} In this study we aimed to investigate the effects of intrahippocampal injection of scopolamine (an antagonist of M1 muscarinic receptors with amnesic effects) on the behavior of rats evaluated on elevated plus-maze. The animals were tested in the plus-maze immediately after the drug injection and re-tested after 24 h without the drug effect. We analyzed the open and closed arms exploration in each session, and also the behavioral profile in each session using the minute by minute analyses. The results showed increases in the open arms exploration to the scopolamine animals in the first session. The minute by minute analyses in this session showed a maintenance of the exploration during the session, conversely to the observed in the saline animals when in the third minute is showed a significant reduction in comparison to the first minute. These results show that the scopolamine leads to impair the mechanism of acquisition and consolidation of the information during the session, without altering the long term memory processes.

Influence of acid functionalization on the cardiopulmonary toxicity of carbon nanotubes and carbon black particles in mice

Engineered carbon nanotubes are being developed for a wide range of industrial and medical applications. Because of their unique properties, nanotubes can impose potentially toxic effects, particularly if they have been modified to express functionally reactive chemical groups on their surface. The present study was designed to evaluate whether acid functionalization (AF) enhanced the cardiopulmonary toxicity of single-walled carbon nanotubes (SWCNT) as well as control carbon black particles. Mice were exposed by oropharyngeal aspiration to 10 or 40 μg of saline-suspended single-walled carbon nanotubes (SWCNTs), acid-functionalized SWCNTs (AF-SWCNTs), ultrafine carbon black (UFCB), AF-UFCB, or 2 μg LPS. 24 hours later, pulmonary inflammatory responses and cardiac effects were assessed by bronchoalveolar lavage and isolated cardiac perfusion respectively, and compared to saline or LPS-instilled animals. Additional mice were assessed for histological changes in lung and heart. Instillation of 40 μg of AF-SWCNTs, UFCB and AF-UFCB increased percentage of pulmonary neutrophils. No significant effects were observed at the lower particle concentration. Sporadic clumps of particles from each treatment group were observed in the small airways and interstitial areas of the lungs according to particle dose. Patches of cellular infiltration and edema in both the small airways and in the interstitium were also observed in the high dose group. Isolated perfused hearts from mice exposed to 40 μg of AF-SWCNTs had significantly lower cardiac functional recovery, greater infarct size, and higher coronary flow rate than other particle-exposed animals and controls, and also exhibited signs of focal cardiac myofiber degeneration. No particles were detected in heart tissue under light microscopy. This study indicates that while acid functionalization increases the pulmonary toxicity of both UFCB and SWCNTs, this treatment caused cardiac effects only with the AF-carbon nanotubes. Further experiments are needed to understand the physico-chemical processes involved in this phenomenon.