Effect of pioglitazone and simvastatin in lipopolysaccharide-induced amyloidogenesis and cognitive impairment in mice: possible role of glutamatergic pathway and oxidative stress.

Abstract:

:Neuroinflammation and β-amyloid (Aβ) deposition in the brain are well known characteristics of neurodegeneration. Diabetes and hypercholesterolemia are the main risk factors leading to memory loss and cognitive impairment. Recently, it was found that statins and thiazolidinediones have promising anti-inflammatory and neuroprotective effects that could delay neurodegeneration and neuronal loss in diabetic and hypercholesterolemic patients. The aim of the present study was to investigate the protective effect of simvastatin, pioglitazone, and their combination in lipopolysaccharide (LPS)-induced neuroinflammation and amyloidogenesis. Mice were divided into five groups: group 1 received 0.9% saline, group 2 received LPS (0.8 mg/kg in saline), group 3 received LPS (0.8 mgl kg)+simvastatin (5 mg/kg in saline), group 4 received LPS (0.8 mg/kg)+pioglitazone (20 mg/kg in saline), group 5 receiving LPS (0.8 mg/kg)+simvastatin (5 mg/kg)+pioglitazone (20 mg/kg). Y-maze and novel object recognition were used to assess the spatial and nonspatial behavioral changes. Nitric oxide levels and glutamate levels were measured to elucidate the anti-glutamatergic and anti-inflammatory effects of the tested drugs. Immunohistochemistry was performed to detect the presence of Aβ1-42 in the mice brain. LPS impaired memory, and increased Aβ deposition, nitric oxide, and glutamate brain levels. Both drugs produced a significant improvement in all parameters. We conclude that simvastatin and pioglitazone may have a protective effect against cognitive impairment induced by LPS, through targeting the glutamatergic and inflammatory pathways, especially in patients having hypercholesterolemia and diabetes.

journal_name

Behav Pharmacol

journal_title

Behavioural pharmacology

authors

Ekladious ST,El Sayed NS

doi

10.1097/FBP.0000000000000407

subject

Has Abstract

pub_date

2019-02-01 00:00:00

pages

5-15

issue

1

eissn

0955-8810

issn

1473-5849

journal_volume

30

pub_type

杂志文章
  • Differential cross-tolerance to the effects of nicotinic acetylcholine receptor drugs in C57BL/6J mice following chronic varenicline.

    abstract::Varenicline is a smoking cessation pharmacotherapy with a presumed mechanism of action of partial efficacy at the α4β2 nicotinic acetylcholine receptor (nAChR); however, the extent to which daily varenicline use leads to changes in nAChR sensitivity is unclear. This study examined the consequences of daily varenicline...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000452

    authors: de Moura FB,McMahon LR

    更新日期:2019-08-01 00:00:00

  • 5-HT mediation of the antiaversive effect of isamoltane injected into the dorsal periaqueductal grey.

    abstract::A previous study from this laboratory reported an antiaversive effect of the beta-adrenoceptor blocker propranolol microinjected into the dorsal periaqueductal grey (DPAG) of the rat, that was antagonized by the 5-HT(2) receptor blocker ritanserin. The present results show that microinjection into the DPAG of isamolta...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/00008877-199102000-00010

    authors: Nogueira RL,Graeff FG

    更新日期:1991-02-01 00:00:00

  • Clonidine and yohimbine in opioid-dependent humans responding under a naloxone novel-response discrimination procedure.

    abstract::Opioid-maintained volunteers were trained to distinguish between a low dose of the opioid antagonist naloxone (0.15 mg/70 kg, i.m.; i.e. Drug A) and placebo (i.e. Drug B), under an instructed novel-response drug discrimination procedure in which subjects identify the drug condition as 'A', 'B', or 'N' (neither A nor B...

    journal_title:Behavioural pharmacology

    pub_type: 临床试验,杂志文章,随机对照试验

    doi:10.1097/00008877-200303000-00001

    authors: Oliveto A,Sevarino K,McCance-Katz E,Benios T,Poling J,Feingold A

    更新日期:2003-03-01 00:00:00

  • Effects of repeated administration of d-amphetamine on agonistic behaviour of isolated male mice.

    abstract::Insufficient research has been carried out on the effects of repeated treatments with psychostimulants on agonistic behaviour. These effects were studied in mice using different schedules of administration and employing a low dose of amphetamine (1.5 mg/kg) which did not produce significant motor disruptions. After tw...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/00008877-199708000-00004

    authors: Moro M,Salvador A,Simón VM

    更新日期:1997-08-01 00:00:00

  • Dissociation of effects of chronic diazepam treatment and withdrawal on hippocampal dialysate 5-HT and mCPP-induced anxiety in rats.

    abstract::Acute (10mg/kg, i.p.) and chronic (10mg/kg/day, i.p. for 10 days) diazepam treatments decreased hippocampal dialysate 5-HT (but not 5-HIAA) concentrations in freely moving rats, suggesting decreased availability of 5-HT to receptors. Twenty-four hours after the last chronic diazepam injection, hippocampal dialysate 5-...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Gibson EL,Barnfield AM,Curzon G

    更新日期:1996-03-01 00:00:00

  • Discriminative stimulus effects of alprazolam and diazepam: generalization to benzodiazepines, antidepressants and buspirone.

    abstract::Rats in one group were trained to discriminate alprazolam (1.0mg/kg, i.p.) and in another group diazepam (3.0mg/kg, i.p.) from saline in a two-lever drug discrimination procedure. Food presentation occurred after 10 consecutive responses on the lever associated either with the training drug or with saline. Alprazolam,...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Wettstein JG,Gauthier B

    更新日期:1992-06-01 00:00:00

  • Personality traits modulate emotional and physiological responses to stress.

    abstract::An individual's susceptibility to psychological and physical disorders associated with chronic stress exposure, for example, cardiovascular and infectious disease, may also be predicted by their reactivity to acute stress. One factor associated with both stress resilience and health outcomes is personality. An underst...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000064

    authors: Childs E,White TL,de Wit H

    更新日期:2014-09-01 00:00:00

  • LY294002, an inhibitor of phosphoinositide 3-kinase given into rat hippocampus impairs acquisition, consolidation and retrieval of memory for one-trial step-down inhibitory avoidance.

    abstract::Adult male Wistar rats were bilaterally implanted with indwelling cannulae in the CA1 region of the dorsal hippocampus. Once recovered from surgery, animals were submitted to one session of step-down inhibitory avoidance training (3.0 s, 0.4 mA footshock). Animals received a 0.5-microl infusion of saline, or of LY2940...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/00008877-200112000-00007

    authors: Barros DM,Mello e Souza T,de Souza MM,Choi H,DeDavid e Silva T,Lenz G,Medina JH,Izquierdo I

    更新日期:2001-12-01 00:00:00

  • Learning impairment by Δ(9)-tetrahydrocannabinol in adolescence is attributable to deficits in chunking.

    abstract::Cannabis is the most popular illicit drug used by adolescents. Yet, there are only a few studies that have examined the effects of cannabis use on learning and memory during this sensitive and important neurodevelopmental stage. Male adolescent Sprague-Dawley rats were treated with Δ(9)-tetrahydrocannabinol (THC, 6 mg...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0b013e32834dbbb1

    authors: Steel RW,Miller JH,Sim DA,Day DJ

    更新日期:2011-12-01 00:00:00

  • Ultra-low dose naltrexone enhances cannabinoid-induced antinociception.

    abstract::Both opioids and cannabinoids have inhibitory effects at micromolar doses, which are mediated by activated receptors coupling to Gi/o-proteins. Surprisingly, the analgesic effects of opioids are enhanced by ultra-low doses (nanomolar to picomolar) of the opioid antagonist, naltrexone. As opioid and cannabinoid systems...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/00008877-200512000-00001

    authors: Paquette J,Olmstead MC

    更新日期:2005-12-01 00:00:00

  • Effects of chronic mild stress on the development of drug dependence in rats.

    abstract::There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures o...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000046

    authors: Papp M,Gruca P,Lason-Tyburkiewicz M,Litwa E,Willner P

    更新日期:2014-09-01 00:00:00

  • Crossover associations of alcohol and smoking, craving and biochemically verified alcohol and nicotine use in heavy drinking smokers.

    abstract::This study examined associations between drinking and smoking prior to treatment (biochemically measured at baseline), alcohol and tobacco craving, and biochemical alcohol and tobacco use during the analog trial period. We conducted a secondary data analysis of a randomized clinical analog trial where participants wit...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000568

    authors: Smith CL,Jenkins G,Burduli E,Tham P,Miguel A,Roll J,Mcpherson S

    更新日期:2020-10-01 00:00:00

  • Phencyclidine-induced stereotyped behaviour and social isolation in rats: a possible animal model of schizophrenia.

    abstract::Phencyclidine (PCP) can induce a model psychosis in humans that mimics the positive and negative symptoms of schizophrenia. The purpose of the present study was to determine whether PCP can induce similar behavioural effects in rats and whether these effects can be alleviated by neuroleptic drug treatment. Rats were t...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Sams-Dodd F

    更新日期:1996-01-01 00:00:00

  • Time-dependent and schedule-dependent effects of dopamine receptor blockade.

    abstract::Rats were trained on one of two multiple random-interval schedules of reinforcement, which contained both ascending and descending reinforcement density sequences. The design of the schedules made it possible to determine whether performance changes in a particular component depended on the reinforcement density in th...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Willner P,Phillips G,Sampson D,Muscat R

    更新日期:1989-01-01 00:00:00

  • How reliable is the behavioural evaluation of dyskinesia in animal models of Parkinson's disease?

    abstract::In spite of the current availability of several pharmacological therapies for the treatment of Parkinson's disease, side effects are invariably manifested during long-term treatment. Dyskinesia, wearing-off and on-off are among the most disabling side effects produced by the dopamine precursor L-dihydroxyphenylalanine...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章,评审

    doi:10.1097/00008877-200609000-00005

    authors: Carta AR,Pinna A,Morelli M

    更新日期:2006-09-01 00:00:00

  • A comparison of the reinforcing efficacy of PCP, the PCP derivatives TCP and BTCP, and cocaine using a progressive ratio schedule in the rat.

    abstract::This study was designed to compare the reinforcing efficacy of PCP (phencyclidine:phenylcyclohexyl-piperidine) and the PCP-derivatives BTCP (N-[1-(2-benzo(b)thiophenyl) cyclohexyl]piperidine) and TCP (N-[1-(2-thienyl)cyclohexyl]-piperidine) to that of cocaine, using a progressive ratio schedule of reinforcement (PR). ...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: French ED,Lopez M,Peper S,Kamenka JM,Roberts DC

    更新日期:1995-04-01 00:00:00

  • Chronic administration of clozapine alleviates reversal-learning impairment in isolation-reared rats.

    abstract::Isolation rearing has been used for inducing schizophrenia-like symptoms in rats. Human schizophrenics have deficits in prefrontal-dysfunction-related cognitive/behavioral flexibility. Rats with lesions of the medial prefrontal cortex perform poorly in reversal learning. It is uncertain whether isolation rearing, howe...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0b013e3280d3ee83

    authors: Li N,Wu X,Li L

    更新日期:2007-03-01 00:00:00

  • Behaviour in the novel environment predicts responsiveness to d-amphetamine in the rat: a multivariate approach.

    abstract::The behaviour of rats in a novel environment was studied using a rapid time-sampling observation procedure followed by a principal component analysis (PCA) of the data. This approach revealed that novel environment behaviour can be described by two factors or principal components. The first factor comprised rearing, s...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Exner M,Clark D

    更新日期:1993-02-01 00:00:00

  • Initial development of a brief assessment of cocaine demand.

    abstract::Cocaine demand is a behavioral economic measure assessing drug reward value and motivation to use drug. The purpose of the current study was to develop a brief assessment of cocaine demand (BACD). Results from the BACD were compared with self-report measures of cocaine use. Participants consisted of treatment-seeking ...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000617

    authors: Yoon JH,de Dios C,Suchting R,Vincent JN,McKay SA,Lane SD,Schmitz JM

    更新日期:2020-12-24 00:00:00

  • Changes in gut microbiota during development of compulsive checking and locomotor sensitization induced by chronic treatment with the dopamine agonist quinpirole.

    abstract::Long-term treatment of rats with the D2/D3 dopamine agonist quinpirole induces compulsive checking (proposed as animal model of obsessive-compulsive disorder) and locomotor sensitization. The mechanisms by which long-term use of quinpirole produces those behavioral transformations are not known. Here we examined wheth...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000363

    authors: Jung TD,Jung PS,Raveendran L,Farbod Y,Dvorkin-Gheva A,Sakic B,Surette MG,Szechtman H

    更新日期:2018-04-01 00:00:00

  • (+)-N-Allylnormetazocine (NANM)-like discriminative stimulus effects of N-methyl-D-aspartate (NMDA) antagonists.

    abstract::The effects of the competitive NMDA antagonists, 2-amino-4,5-(1,2-cyclohexyl)-7-phosphonoheptanoic acid (NPC 12626) and 3-(2-carboxypiperazin-4-yl) propyl-l-phosphonic acid (CPP), were compared to those of the noncompetitive NMDA antagonists, phencyclidine (PCP) and (+)-5-methyl-10, 11-dihydro-5H-dibenzo (a,d) cyclohe...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Willetts J,Rice A,Balster RL

    更新日期:1990-01-01 00:00:00

  • Behavioral effects in adult rats of chronic prepubertal treatment with the cannabinoid receptor agonist WIN 55,212-2.

    abstract::Human and animal studies provide evidence for vulnerable periods of brain development for deleterious effects of cannabinoids. We have recently shown that pubertal chronic cannabinoid treatment leads to long-lasting behavioral deficits, whereas a comparable treatment in adult rats did not affect the animals' behavior....

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/00008877-200509000-00018

    authors: Schneider M,Drews E,Koch M

    更新日期:2005-09-01 00:00:00

  • Injection of SCH 23390 into the ventral tegmental area blocks the development of neurochemical but not behavioral sensitization to cocaine.

    abstract::Previous studies have indicated that dopamine D1 receptors in the ventral tegmental area (VTA) may play an important role in the development of sensitization to amphetamine. The present study was designed to determine if D1 receptors are also important in the development of cocaine-induced behavioral and neurochemical...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Steketee JD

    更新日期:1998-02-01 00:00:00

  • A comparison of the predictive therapeutic and undesired side-effects of the NMDA receptor antagonist, memantine, in mice.

    abstract::Memantine (1-amino-3,5-dimethyl-adamantane) is the only clinically used NMDA (N-methyl-D-aspartate) glutamate receptor antagonist. The present experiments were carried out to compare the dose-response for memantine's predictive therapeutic and side-effects in a variety of tests in C57BL/6J/Han mice, and to elucidate i...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/00008877-200505000-00004

    authors: Kos T,Popik P

    更新日期:2005-05-01 00:00:00

  • Does potency determine amnestic effects of benzodiazepines? A dose-response comparison of flunitrazepam and nitrazepam.

    abstract::This study was designed to explore whether differences in the psychomotor, subjective and memory effects of different benzodiazepines (BDZ) relate to differences in their potencies. Two BDZs with similar kinetics but different potencies were compared. Flunitrazepam (0.5 and 1.0mg, nitrazepam (5 and 10mg) or placebo we...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:

    authors: Pompéia S,Gorenstein C,Curran HV

    更新日期:1996-11-01 00:00:00

  • Assessment of executive function using the Tinkertoy test.

    abstract::The Tinkertoy test (TTT) has often been used to assess executive function. Despite its clinical importance, there are few published normative data for it. Thus, the primary aim of this study was to fill this gap. Moreover, as there exists a sex difference in many cognitive abilities and neuropsychological tests, a sec...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000434

    authors: Lambert M,Stenger J,Bielajew C

    更新日期:2018-12-01 00:00:00

  • First evidence that drugs of abuse produce behavioral sensitization and cross sensitization in planarians.

    abstract::Behavioral sensitization in mammals, including humans, is sensitive to factors such as administration route, testing environment, and pharmacokinetic confounds, unrelated to the drugs themselves that are difficult to eliminate. Simpler animals less susceptible to these confounding influences may be advantageous substi...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0b013e32833b0098

    authors: Rawls SM,Patil T,Yuvasheva E,Raffa RB

    更新日期:2010-07-01 00:00:00

  • Chronic treatment with Delta(9)-tetrahydrocannabinol impairs spatial memory and reduces zif268 expression in the mouse forebrain.

    abstract::Few studies have investigated the effects of chronic cannabinoid exposure on memory performance and whether tolerance occurs to cannabinoid-induced memory impairment. Here, we studied the effects of repeated exposure to Delta-tetrahydrocannabinol (THC: 1 mg/kg) on spatial memory and zif268 expression in mice. One grou...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0b013e3283242f6a

    authors: Boucher AA,Vivier L,Metna-Laurent M,Brayda-Bruno L,Mons N,Arnold JC,Micheau J

    更新日期:2009-02-01 00:00:00

  • Early social isolation augments alcohol consumption in rats.

    abstract::There is a considerable degree of individual vulnerability for alcohol use disorder (AUD) as only a subpopulation of individuals who regularly consume alcohol develop AUD. It is therefore very important to understand the factors and mechanisms that contribute towards the individual risk for AUD. In this respect, socia...

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/FBP.0000000000000165

    authors: Lesscher HM,Spoelder M,Rotte MD,Janssen MJ,Hesseling P,Lozeman-van't Klooster JG,Baars AM,Vanderschuren LJ

    更新日期:2015-10-01 00:00:00

  • Spatial and associative learning deficits induced by neonatal excitotoxic hippocampal damage in rats: further evaluation of an animal model of schizophrenia.

    abstract::Neonatal ventral hippocampal lesions in the rat result in post-pubertal onset of behavioural abnormalities, modelling some aspects of schizophrenia. We further assessed the behavioural effects of neonatal lesions in rats in a variety of cognitive tasks and in the prepulse inhibition (PPI) of startle response paradigm....

    journal_title:Behavioural pharmacology

    pub_type: 杂志文章

    doi:10.1097/00008877-200006000-00009

    authors: Le Pen G,Grottick AJ,Higgins GA,Martin JR,Jenck F,Moreau JL

    更新日期:2000-06-01 00:00:00