Medicine and Health Sciences Commons^™

Assessing The Impact Of Lipopolysaccharide On Learning And Memory In Rats, Anahat Luthra

Undergraduate Student Research Internships Conference

The immune system and the central nervous system (CNS) have a bi-direction relationship, modulating one another.⁴ Proinflammatory cytokines released from CNS immune cells have an impact on cognitive processes such as learning and memory.¹ Liposaccharide (LPS), a cell wall component of Gram-negative bacteria, which is used to activate proinflammatory cytokine release has been found to impact learning and memory processes, such as in the anticipatory nausea paradigm (ANP).² Anticipatory nausea and vomiting is that which may occur before a chemotherapy treatment session begins in a patient who has had chemotherapy before. It is caused by triggers like …

Effects Of Acute And Chronic Nicotine Administration On Choice Of Probabilistic Outcomes, Katya A. Nolder

Graduate Theses, Dissertations, and Problem Reports

Risky choice can be operationally defined as the choice for a larger, uncertain reinforcer over a smaller, certain reinforcer. Research suggests smokers engage in more risky or maladaptive decisions when compared to nonsmokers. The relation between nicotine and risky choice could benefit from further investigation, since nicotine is the active substance of tobacco products that maintains tobacco addiction. Acute nicotine administration has shown to alter risky choice; however, since the everyday smoker uses nicotine repeatedly, more research on chronic administration is warranted and would allow for assessment of tolerance or sensitization of these effects. The present study investigated effects of …

Validation And Optimisation Of A Touchscreen Progressive Ratio Test Of Motivation In Male Rats, Jonathan M. Hailwood, Christopher J. Heath, Trevor W. Robbins, Lisa M. Saksida, Timothy J. Bussey

Brain and Mind Institute Researchers' Publications

© 2018, The Author(s). Rationale: Across species, effort-related motivation can be assessed by testing behaviour under a progressive ratio (PR) schedule of reinforcement. However, to date, PR tasks for rodents have been available using traditional operant response systems only. Objectives: Touchscreen operant response systems allow the assessment of behaviour in laboratory rodents, using tasks that share high face validity with the computerised assessments used in humans. Here, we sought to optimise a rat touchscreen variant of PR and validate it by assessing the effects of a number of manipulations known to affect PR performance in non-touchscreen paradigms. Methods: Separate groups …

Mediodorsal Thalamic Neurons Mirror The Activity Of Medial Prefrontal Neurons Responding To Movement And Reinforcement During A Dynamic Dnmtp Task, Rikki L.A. Miller Phd, Miranda J. Francoeur, Brett M. Gibson, Robert G. Mair

Faculty Publications

The mediodorsal nucleus (MD) interacts with medial prefrontal cortex (mPFC) to support learning and adaptive decision-making. MD receives driver (layer 5) and modulatory (layer 6) projections from PFC and is the main source of driver thalamic projections to middle cortical layers of PFC. Little is known about the activity of MD neurons and their influence on PFC during decision-making. We recorded MD neurons in rats performing a dynamic delayed nonmatching to position (dDNMTP) task and compared results to a previous study of mPFC with the same task (Onos et al., 2016). Criterion event-related responses were observed for 22% …

Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for …

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Jarrod Bailey, PhD

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …

Rat Behavioral Discrimination Of Temporal Cues In Species-Specific Vocalization, Kevin Mathews Tharakan

Honors Scholar Theses

Current behavioral and neurophysiologic studies propose that many animals can detect and discriminate the invariant statistics found in natural vocalization (Geffen et. al., 2011; Rodriguez et al., 2010). However, according to current research the neuronal mechanisms underlying the sound discrimination process is still unclear. While numerous auditory statistics have been manipulated, none has varied the temporal and tonal frequency cues independently in their synthetic call sequences, thus it is still uncertain whether rats rely on temporal cues in the sound envelope for communication.

The aim of this research is to determine whether or not rats rely on temporal cues in …

Predicting Human Drug Toxicity And Safety Via Animal Tests: Can Any One Species Predict Drug Toxicity In Any Other, And Do Monkeys Help?, Jarrod Bailey, Michelle Thew, Michael Balls

Laboratory Experiments Collection

Animals are still widely used in drug development and safety tests, despite evidence for their lack of predictive value. In this regard, we recently showed, by producing Likelihood Ratios (LRs) for an extensive data set of over 3,000 drugs with both animal and human data, that the absence of toxicity in animals provides little or virtually no evidential weight that adverse drug reactions will also be absent in humans. While our analyses suggest that the presence of toxicity in one species may sometimes add evidential weight for risk of toxicity in another, the LRs are extremely inconsistent, varying substantially for …

Determining The Critical Window Of Influence Of Pcb Perinatally On Behavioral And Hormonal Development In Sprague-Dawley Rat Pups, Natalie Sommerville, Lee A. Meserve, Howard C. Cromwell

Honors Projects

Polychlorinated biphenyls (PCB) had widespread use in the United States in commercial manufacturing in the United States until the late 1970s. Even though they were banned, measurable amounts can still be found in the environment and food sources. PCB has known effects on altering hormone development and behavior in the species Rattus norvegicus. To determine the most crucial developmental time of exposure to PCB in Sprague-Dawley rat pups, rat pups were exposed to PCB at differing weeks of either gestation period or the first postnatal week. Behavioral tests were performed for the different rat pups, as well as blood …

An Analysis Of The Use Of Animal Models In Predicting Human Toxicology And Drug Safety, Jarrod Bailey, Michelle Thew, Michael Balls

Experimentation Collection

Animal use continues to be central to preclinical drug development, in spite of a lack of its demonstrable validity. The current nadir of new drug approvals and the drying-up of pipelines may be a direct consequence of this. To estimate the evidential weight given by animal data to the probability that a new drug may be toxic to humans, we have calculated Likelihood Ratios (LRs) for an extensive data set of 2,366 drugs, for which both animal and human data are available, including tissue-level effects and MedDRA Level 1–4 biomedical observations. This was done for three preclinical species (rat, mouse …

Extracellular Chaperones Prevent Aβ42-Induced Toxicity In Rat Brains, Roberta Cascella, Simona Conti, Francesca Tatini, Elisa Evangelisti, Tania Scartabelli, Fiorella Casamenti, Mark R. Wilson, Fabrizio Chiti, Cristina Cecchi

Faculty of Science, Medicine and Health - Papers: part A

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by cognitive decline, formation of the extracellular amyloid β (Aβ42) plaques, neuronal and synapse loss, and activated microglia and astrocytes. Extracellular chaperones, which are known to inhibit amyloid fibril formation and promote clearance of misfolded aggregates, have recently been shown to reduce efficiently the toxicity of HypF-N misfolded oligomers to immortalised cell lines, by binding and clustering them into large species. However, the role of extracellular chaperones on Aβ oligomer toxicity remains unclear, with reports often appearing contradictory. In this study we microinjected into the hippocampus of rat brains Aβ42 oligomers …

Genomic Homeostasis Is Dysregulated In Favour Of Apoptosis In The Colonic Epithelium Of The Azoxymethane Treated Rat, Caroline A. Kerr, Barney M. Hines, Janet M. Shaw, Robert Dunne, Lauren M. Bragg, Julie Clarke, Trevor Lockett, Richard Head

Faculty of Science, Medicine and Health - Papers: part A

Background The acute response to genotoxic carcinogens in rats is an important model for researching cancer initiation events. In this report we define the normal rat colonic epithelium by describing transcriptional events along the anterior-posterior axis and then investigate the acute effects of azoxymethane (AOM) on gene expression, with a particular emphasis on pathways associated with the maintenance of genomic integrity in the proximal and distal compartments using whole genome expression microarrays. Results There are large transcriptional changes that occur in epithelial gene expression along the anterior-posterior axis of the normal healthy rat colon. AOM administration superimposes substantial changes on …

The Effects Of Insufflation Conditions On Rat Mesothelium, Andrew K. Davey, Jessica Hayward, Jean K. Marshall, Anthony E. Woods

Faculty of Science, Medicine and Health - Papers: part A

Aim. The aim of this investigation was to examine the alterations in the peritoneum after cold dry CO2, heated dry CO2, and humidified heated CO2 at pressures equivalent to intraperitoneal pressures used in human laparoscopy. Methods. Eighteen rats were divided into 4 treatment groups—group 1: untreated control; group 2: insufflation with cold dry CO2; group 3: insufflation with heated, dry CO2; group 4: insufflation with heated and humidified CO2. The abdomen was insufflated to 5 mm/Hg (flow rate 50 mL/min) for 2 h. Twelve hours later, tissue samples were collected for analysis by light microscopy (LM) and scanning electron microscopy …

Neuroanatomical Substrates Of The Disruptive Effect Of Olanzapine On Rat Maternal Behavior As Revealed By C-Fos Immunoreactivity, Changjiu Zhao, Ming Li

Department of Psychology: Faculty Publications

Olanzapine is one of the most widely prescribed atypical antipsychotic drugs in the treatment of schizophrenia. Besides its well-known side effect on weight gain, it may also impair human parental behavior. In this study, we took a preclinical approach to examine the behavioral effects of olanzapine on rat maternal behavior and investigated the associated neural basis using the c-Fos immunohistochemistry. On postpartum Days 6–8, Sprague-Dawley mother rats were given a single injection of sterile water or olanzapine (1.0, 3.0 or 5.0 mg/kg, sc). Maternal behavior was tested 2 h later, after which rats were sacrificed and brain tissues were collected. …

Drug–Drug Conditioning Between Citalopram And Haloperidol Or Olanzapine In A Conditioned Avoidance Response Model: Implications For Polypharmacy In Schizophrenia, Nathan L. Sparkman, Ming Li

Department of Psychology: Faculty Publications

Patients with schizophrenia often have anxiety and depression, and thus are treated with multiple psychotherapeutic medications. This practice of polypharmacy increases the possibility for drug–drug interactions. However, the pharmacological and behavioral mechanisms underlying drug–drug interactions in schizophrenia remain poorly understood. In the present study, we adopted a preclinical approach and examined a less known behavioral mechanism, drug–drug conditioning (DDC) between haloperidol (a typical antipsychotic) or olanzapine (atypical antipsychotic) and citalopram (a selective serotonin reuptake inhibitor). A rat two-way conditioned avoidance response paradigm was used to measure antipsychotic activity and determine how DDC may alter the antipsychotic efficacy in this model. …

Effects Of Simvastatin And 6-Hydroxydopamine Lesion On Histaminergic H1 Receptor Binding In Rat Brains, C H. Hu, C Deng, Xu-Feng Huang, J Chen, Q Wang

Xu-Feng Huang

No abstract provided.

Effect Of Chronic Treatment With Clozapine And Haloperidol On 5- Ht2a And 2c Receptor Mrna Expression In The Rat Brain, Xu-Feng Huang, Qing Wang, Yean Yeow Tan

Xu-Feng Huang

No abstract provided.

Chronic Treatment With Simvastatin Upregulates Muscarinic M1/4 Receptor Binding In The Rat Brain, Kelly Newell, P Wong, Xu-Feng Huang, Qing Wang, Wilfred Yeo, P Wang, Weihai Ying, Midori Yenari, Ayse Zengin

Xu-Feng Huang

Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [3H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [3H]pirenzepine binding, predominantly in the prefrontal cortex (171%, P<0.001), primary motor cortex (153%, P=0.001), cingulate cortex (109%, P<0.001), hippocampus (138%, P …

Effects Of Chronic Treatment Of Olanzapine And Haloperidol On Peptide Yy Binding Densities In The Rat Brain, Xu-Feng Huang, Qing Wang

Xu-Feng Huang

This study examined regional changes of peptide YY (PYY) binding densities in the rat brain after chronic administration of olanzapine (1.2 mg/kg/day and haloperidol (2.0 mg/kg/day)for 36 days. PYY binding densities and distributions were detected by [125I] binding autoradiography after ratswere sacrificed either 2 h or 48 h after the last drug administration to examine both immediate and delayed effects following the drugwithdrawal. Following 2 h of drug administration, it showed that olanzapine administration significantly decreased PYY binding densities, predominantly in the posterodorsal part of medial amygdaloid nucleus (52 percent, pb0.05), dorsal part of medial geniculate nucleus (56 percent, pb0.05), …

Effects Of Antipsychotic Medication On Muscarinic M1 Receptor Mrna Expression In The Rat Brain, Kelly Newell, Xu-Feng Huang, Katerina Zavitsanou, Chao Deng, Mei Han

Xu-Feng Huang

Alterations in muscarinic M1 receptor protein and mRNA expression have been revealed in post-mortem brains of schizophrenia patients. Most patients had been treated with antipsychotics, so medication effects cannot be excluded as a possible explanation for these results. With in situ hybridization, this study investigated M1 receptor mRNA expression in rats treated with the typical antipsychotic haloperidol (0.3 mg/kg/day) and the atypical antipsychotics olanzapine (1.5 mg/kg/day) and aripiprazole (2.25 mg/kg/day) for 1 or 12 weeks. Compared with the control group, haloperidol significantly increased (13-21%, P < 0.05) M1 mRNA expression in the CA1, CA2, and CA3 regions of the hippocampus after both 1 and 12 weeks of treatment, and it also increased (17%, P < 0.01) M1 mRNA expression in the substantia nigra compacta after 1 week of treatment. Olanzapine significantly increased (14-22%, P < 0.05) M1 mRNA expression in the hippocampus (CA1, CA2, and CA3) and substantia nigra compacta after 12 weeks of treatment, but not after 1 week. Aripiprazole significantly increased (17%, P < 0.01) M1 mRNA expression in the hippocampus (CA1) after both 1 and 12 week treatments and increased (12%, P < 0.05) M1 mRNA expression in the nucleus accumbens after 1 week of treatment. Despite their different affinities for muscarinic M1 receptors, all three antipsychotic medications induced a similar trend of change in M1 mRNA expression in selected brain regions. These data suggest that the decreased M1 receptor protein and mRNA expression observed in schizophrenia patients is unlikely to be a consequence of drug treatments and implicates muscarinic M1 receptors in the pharmacotherapy of the disease. © 2007 Wiley-Liss, Inc.

Fatty Acids Differentially Affect 5-Ht2 Receptor And Transporter Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois

Xu-Feng Huang

No abstract provided.

High Dose Of Simvastatin Induces Hyperlocomotive And Anxiolytic-Like Activities: The Association With The Up-Regulation Of Nmda Receptor Binding In The Rat Brain, Kelly Newell, Xu-Feng Huang, Chao Deng, Qing Wang, Einar Wilder-Smith, Yun Li, Ying Lu, Ayse Zengin, Guo-Yuan Yang, Heng Zhao

Xu-Feng Huang

Statins are widely being used for the treatment of a variety of conditions beyond their original indication for lowering cholesterol. We have previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate locomotor and anxiety effects along with the regional changes of N-methyl-d-aspartate (NMDA) receptors in the rat brain after 4-week administration of simvastatin. Hyperlocomotive and anxiolytic-like activities in the rat were observed after chronic administration of high dose simvastatin (10 mg/kg/day). Distributions and alterations of NMDA receptors in the post-mortem rat brain were detected by [3H] MK-801 binding autoradiography. Simvastatin increased [3H] …

Olanzapine Differentially Affects 5-Ht2a And 2c Receptor Mrna Expression In The Rat Brain, Xinyi Huang, Xu-Feng Huang, Katerina Zavitsanou, Chao Deng, Mei Han

Xu-Feng Huang

No abstract provided.

A High N-6 Polyunsaturated Fatty Acid Diet Reduces Muscarinic M2/M4 Receptor Binding In The Rat Brain, Xu-Feng Huang, Chao Deng, Warren Bell, Teresa Du Bois

Xu-Feng Huang

No abstract provided.

Effects Of Typical And Atypical Antipsychotic Drugs On Rat Brain Muscarinic Receptors, Van Nguyen, Xu-Feng Huang, Katerina Zavitsanou, Mei Han

Xu-Feng Huang

No abstract provided.

Parametric Studies Of Antipsychotic-Induced Sensitization In The Conditioned Avoidance Response Model: Roles Of Number Of Drug Exposure, Drug Dose, And Test–Retest Interval, Natashia Swalve, Ming Li

Department of Psychology: Faculty Publications

Repeated haloperidol and olanzapine treatment produces an enhanced disruption of avoidance responding, a validated measure of antipsychotic activity. Experimental parameters affecting this sensitization-like effect have not been thoroughly examined. The present study investigated the role of three parameters (number of injections, dose, and interval between initial exposure and challenge) in antipsychotic sensitization in the conditioned avoidance response paradigm. Well-trained Sprague–Dawley rats received different numbers of drug treatment (1–5 days) or different doses of haloperidol (0.025–0.10 mg/kg, subcutaneously) or olanzapine (0.5–2.0 mg/kg, subcutaneously). After certain time intervals (4, 10 or 17 days), they were tested for the expression of haloperidol or …

Differential Effects Of Acute Amphetamine And Phencyclidine Treatment And Withdrawal From Repeated Amphetamine Or Phencyclidine Treatment On Social Interaction And Social Memory In Rats, Ming Li, Wei He, Rebecca Munro

Department of Psychology: Faculty Publications

Although animal models based on amphetamine (AMPH) or phencyclidine (PCP) treatment have been used extensively to study the neurobiological and behavioral characteristics of schizophrenia, there are conflicting reports regarding their validity in modeling the negative symptoms and cognitive deficits of schizophrenia. The present study examined how acute AMPH or PCP treatment (Experiment 1) and withdrawal from repeated AMPH treatment (Experiment 2) or PCP treatment (Experiment 3) affects social behavior and social recognition memory in male Sprague-Dawley rats. Each subject was tested on two consecutive days. On the first day, the rats were tested four times (5 min/each) at 10-min intervals …

Dietary Fish Oil Reduces Skeletal Muscle Oxygen Consumption, Provides Fatigue Resistance And Improves Contractile Recovery In The Rat In Vivo Hindlimb, Gregory E. Peoples, Peter L. Mclennan

Faculty of Health and Behavioural Sciences - Papers (Archive)

Dietary fish oil modulates skeletal muscle membrane fatty acid composition. Similar changes in heart membrane composition modulate myocardial oxygen consumption and enhance mechanical performance. The rat in vivo autologous perfused hindlimb was used to investigate the influence of membrane composition on skeletal muscle function. Male Wistar rats were fed either saturated fat (SF), n-6 PUFA (linoleic acid rich) or n-3 PUFA (fish oil) diets for 8 weeks. Hindlimb skeletal muscle perfused using the animal’s own blood was stimulated via the sciatic nerve (1 Hz, 6-12 V, 0·05 ms) to contract in repeated 10 min bouts. The n-3 PUFA diet markedly …

Effects Of Simvastatin And 6-Hydroxydopamine Lesion On Histaminergic H1 Receptor Binding In Rat Brains, C H. Hu, C Deng, Xu-Feng Huang, J Chen, Q Wang

Faculty of Health and Behavioural Sciences - Papers (Archive)

No abstract provided.

Effects Of Dexamethasone On Posterior Capsule Opacification-Like Changes In A Rat Lens Explant Model, Kylie Mansfield, Anna Cerra, Coral Chamberlain

Faculty of Science, Medicine and Health - Papers: part A

Purpose: Many patients whose sight is initially restored by cataract surgery eventually suffer secondary loss of vision because of posterior capsule opacification (PCO; after-cataract), a condition in which lens epithelial cells left behind at surgery become aberrant and migrate into the light path. The aim of this study was to determine whether dexamethasone (DEX), an anti-inflammatory agent widely used before and after cataract surgery, influences the behavior of lens cells under conditions relevant to PCO development.

Methods: An established rat PCO model was used in which explanted epithelial cells attached to the lens capsule are exposed sequentially to TGFβ2 and …