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https://www.readbyqxmd.com/read/27858407/preclinical-imaging-anesthesia-in-rodents
#1
Giancarlo Vesce, Fabiana Micieli, Ludovica Chiavaccini
Despite the outstanding progress achieved by preclinical imaging science, laboratory animal anesthesia remains quite stationary. Ninety percent of preclinical imaging studies are carried on small rodents (mice and rats) anesthetized by outdated injectable and/or inhalation agents. A need for imaging awake (conscious) animals is questionably registered mainly for brain research, for phMRI and for accomplishing pain and analgesia studies. A need for improving current rodent anesthesia protocols and for enforcing the 3Rs paradigm is sought...
November 18, 2016: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27725212/tak-063-a-phosphodiesterase-10a-inhibitor-modulates-neuronal-activity-in-various-brain-regions-in-phmri-and-eeg-studies-with-and-without-ketamine-challenge
#2
Yoshiro Tomimatsu, Diana Cash, Motohisa Suzuki, Kazunori Suzuki, Michel Bernanos, Camilla Simmons, Steven C R Williams, Haruhide Kimura
TAK-063 is a selective phosphodiesterase 10A (PDE10A) inhibitor that produces potent antipsychotic-like and pro-cognitive effects at 0.3mg/kg (26% PDE10A occupancy in rats) or higher in rodents through the balanced activation of the direct and indirect pathways of striatal medium spiny neurons (MSNs). In this study, we evaluated the specific binding of TAK-063 using in vitro autoradiography (ARG) and the modulation of brain activity using pharmacological magnetic resonance imaging (phMRI) and electroencephalography (EEG)...
December 17, 2016: Neuroscience
https://www.readbyqxmd.com/read/27133029/comparing-the-actions-of-lanicemine-and-ketamine-in-depression-key-role-of-the-anterior-cingulate
#3
Darragh Downey, Arpan Dutta, Shane McKie, Gerard R Dawson, Colin T Dourish, Kevin Craig, Mark A Smith, Dennis J McCarthy, Catherine J Harmer, Guy M Goodwin, Steve Williams, J F William Deakin
Intravenous infusion of lanicemine (formerly AZD6765), a low trapping non-selective N-methyl-D-aspartate (NMDA) receptor antagonist, induces antidepressant effects with a similar time course to ketamine. We investigated whether a single dose lanicemine infusion would reproduce the previously reported decrease in subgenual anterior cingulate cortex (sgACC) activity evoked by ketamine, a potential mechanism of antidepressant efficacy. Sixty un-medicated adults meeting the criteria for major depressive disorder were randomly assigned to receive constant intravenous infusions of ketamine, lanicemine or saline during a 60min pharmacological magnetic resonance imaging (phMRI) scan...
June 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27014046/random-forest-segregation-of-drug-responses-may-define-regions-of-biological-significance
#4
Qasim Bukhari, David Borsook, Markus Rudin, Lino Becerra
The ability to assess brain responses in unsupervised manner based on fMRI measure has remained a challenge. Here we have applied the Random Forest (RF) method to detect differences in the pharmacological MRI (phMRI) response in rats to treatment with an analgesic drug (buprenorphine) as compared to control (saline). Three groups of animals were studied: two groups treated with different doses of the opioid buprenorphine, low (LD), and high dose (HD), and one receiving saline. PhMRI responses were evaluated in 45 brain regions and RF analysis was applied to allocate rats to the individual treatment groups...
2016: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/26796682/comparison-of-seven-different-anesthesia-protocols-for-nicotine-pharmacologic-magnetic-resonance-imaging-in-rat
#5
Jaakko Paasonen, Raimo A Salo, Artem Shatillo, Markus M Forsberg, Johanna Närväinen, Joanna K Huttunen, Olli Gröhn
Pharmacologic MRI (phMRI) is a non-invasive in vivo imaging method, which can evaluate the drug effects on the brain and provide complementary information to ex vivo techniques. The preclinical phMRI studies usually require anesthesia to reduce the motion and stress of the animals. The anesthesia, however, is a crucial part of the experimental design, as it may modulate the neural drug-induced (de)activation and hemodynamic coupling. Therefore, the aim of the present study was to address this methodologic question by performing phMRI experiments with five anesthetics (α-chloralose, isoflurane, medetomidine, thiobutabarbital, and urethane) and seven anesthesia protocols...
March 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/26689424/a-method-for-accurate-ph-mapping-with-chemical-exchange-saturation-transfer-cest-mri
#6
Phillip Zhe Sun, Gang Xiao, Iris Yuwen Zhou, Yingkun Guo, Renhua Wu
Chemical exchange saturation transfer (CEST) MRI holds enormous promise for imaging pH. Whereas the routine CEST-weighted MRI contrast is complex and susceptible to confounding factors such as labile proton ratio, chemical shift, bulk water relaxation and RF saturation, ratiometric CEST imaging simplifies pH determination. However, the conventional ratiometric CEST (RCEST) MRI approach is limited to CEST agents with multiple exchangeable groups. To address this limitation, RF power-based ratiometric CEST (PRCEST) imaging has been proposed that ratios CEST effects obtained under different RF power levels...
May 2016: Contrast Media & Molecular Imaging
https://www.readbyqxmd.com/read/26539115/the-power-of-using-functional-fmri-on-small-rodents-to-study-brain-pharmacology-and-disease
#7
REVIEW
Elisabeth Jonckers, Disha Shah, Julie Hamaide, Marleen Verhoye, Annemie Van der Linden
Functional magnetic resonance imaging (fMRI) is an excellent tool to study the effect of pharmacological modulations on brain function in a non-invasive and longitudinal manner. We introduce several blood oxygenation level dependent (BOLD) fMRI techniques, including resting state (rsfMRI), stimulus-evoked (st-fMRI), and pharmacological MRI (phMRI). Respectively, these techniques permit the assessment of functional connectivity during rest as well as brain activation triggered by sensory stimulation and/or a pharmacological challenge...
2015: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/26329611/pharmacological-mri-phmri-of-the-human-central-nervous-system
#8
REVIEW
H Lanfermann, C Schindler, J Jordan, N Krug, P Raab
Pharmacological magnetic resonance imaging (phMRI) of the central nervous system (CNS) addresses the increasing demands in the biopharma industry for new methods that can accurately predict, as early as possible, whether novel CNS agents will be effective and safe. Imaging of physiological and molecular-level function can provide a more direct measure of a drug mechanism of action, enabling more predictive measures of drug activity. The availability of phMRI of the nervous system within the professional infrastructure of the Clinical Research Center (CRC) Hannover as proof of concept center ensures that advances in basic science progress swiftly into benefits for patients...
October 2015: Clinical Neuroradiology
https://www.readbyqxmd.com/read/26192543/neurovascular-and-neuroimaging-effects-of-the-hallucinogenic-serotonin-receptor-agonist-psilocin-in-the-rat-brain
#9
Aisling Spain, Clare Howarth, Alexandre A Khrapitchev, Trevor Sharp, Nicola R Sibson, Chris Martin
The development of pharmacological magnetic resonance imaging (phMRI) has presented the opportunity for investigation of the neurophysiological effects of drugs in vivo. Psilocin, a hallucinogen metabolised from psilocybin, was recently reported to evoke brain region-specific, phMRI signal changes in humans. The present study investigated the effects of psilocin in a rat model using phMRI and then probed the relationship between neuronal and haemodynamic responses using a multimodal measurement preparation...
December 2015: Neuropharmacology
https://www.readbyqxmd.com/read/25999812/phmri-methodological-considerations-for-mitigating-potential-confounding-factors
#10
REVIEW
Julius H Bourke, Matthew B Wall
Pharmacological Magnetic Resonance Imaging (phMRI) is a variant of conventional MRI that adds pharmacological manipulations in order to study the effects of drugs, or uses pharmacological probes to investigate basic or applied (e.g., clinical) neuroscience questions. Issues that may confound the interpretation of results from various types of phMRI studies are briefly discussed, and a set of methodological strategies that can mitigate these problems are described. These include strategies that can be employed at every stage of investigation, from study design to interpretation of resulting data, and additional techniques suited for use with clinical populations are also featured...
2015: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/25980482/ketamine-induces-a-robust-whole-brain-connectivity-pattern-that-can-be-differentially-modulated-by-drugs-of-different-mechanism-and-clinical-profile
#11
R Joules, O M Doyle, A J Schwarz, O G O'Daly, M Brammer, S C Williams, M A Mehta
Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release...
November 2015: Psychopharmacology
https://www.readbyqxmd.com/read/25724758/-domain-gauges-a-reference-system-for-multivariate-profiling-of-brain-fmri-activation-patterns-induced-by-psychoactive-drugs-in-rats
#12
Andreas Bruns, Thomas Mueggler, Basil Künnecke, Céline Risterucci, Eric P Prinssen, Joseph G Wettstein, Markus von Kienlin
Pharmacological magnetic resonance imaging (phMRI) of the brain has become a widely used tool in both preclinical and clinical drug research. One of its challenges is to condense the observed complex drug-induced brain-activation patterns into semantically meaningful metrics that can then serve as a basis for informed decision making. To aid interpretation of spatially distributed activation patterns, we propose here a set of multivariate metrics termed "domain gauges", which have been calibrated based on different classes of marketed or validated reference drugs...
May 15, 2015: NeuroImage
https://www.readbyqxmd.com/read/25612063/pharmacological-mri-response-to-a-selective-dopamine-transporter-inhibitor-gbr12909-in-awake-and-anesthetized-rats
#13
Yuto Kashiwagi, Takemi Rokugawa, Tomomi Yamada, Atsushi Obata, Hiroshi Watabe, Yoshichika Yoshioka, Kohji Abe
Pharmacological magnetic resonance imaging (phMRI) is a powerful tool for imaging the effects of drugs on brain activity. In preclinical phMRI studies, general anesthesia used for minimizing head movements is thought to influence the phMRI responses to drugs. In this study we investigated the phMRI responses to a selective dopamine transporter (DAT) inhibitor, GBR12909, and a dopamine (DA) releaser, d-amphetamine (AMPH), in the isoflurane anesthetized and awake rats using a relative cerebral blood volume (rCBV) method...
April 2015: Synapse
https://www.readbyqxmd.com/read/25585682/a-systematic-review-of-physiological-methods-in-rodent-pharmacological-mri-studies
#14
REVIEW
Jennifer X Haensel, Aisling Spain, Chris Martin
RATIONALE: Pharmacological magnetic resonance imaging (phMRI) provides an approach to study effects of drug challenges on brain processes. Elucidating mechanisms of drug action helps us to better understand the workings of neurotransmitter systems, map brain function or facilitate drug development. phMRI is increasingly used in preclinical research employing rodent models; however, data interpretation and integration are complicated by the use of different experimental approaches between laboratories...
February 2015: Psychopharmacology
https://www.readbyqxmd.com/read/25443764/pharmacologic-mri-phmri-as-a-tool-to-differentiate-parkinson-s-disease-related-from-age-related-changes-in-basal-ganglia-function
#15
Anders H Andersen, Peter A Hardy, Eric Forman, Greg A Gerhardt, Don M Gash, Richard C Grondin, Zhiming Zhang
The prevalence of both parkinsonian signs and Parkinson's disease (PD) per se increases with age. Although the pathophysiology of PD has been studied extensively, less is known about the functional changes taking place in the basal ganglia circuitry with age. To specifically address this issue, 3 groups of rhesus macaques were studied: normal middle-aged animals (used as controls), middle-aged animals with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism, and aged animals (>20 years old) with declines in motor function...
February 2015: Neurobiology of Aging
https://www.readbyqxmd.com/read/25394786/dopaminergic-system-dysfunction-in-recreational-dexamphetamine-users
#16
Anouk Schrantee, Lena Václavů, Dennis F R Heijtel, Matthan W A Caan, Willy Gsell, Paul J Lucassen, Aart J Nederveen, Jan Booij, Liesbeth Reneman
Dexamphetamine (dAMPH) is a stimulant drug that is widely used recreationally as well as for the treatment of attention-deficit hyperactivity disorder (ADHD). Although animal studies have shown neurotoxic effects of dAMPH on the dopaminergic system, little is known about such effects on the human brain. Here, we studied the dopaminergic system at multiple physiological levels in recreational dAMPH users and age, gender, and IQ-matched dAMPH-naïve healthy controls. We assessed baseline D2/3 receptor availability, in addition to changes in dopamine (DA) release using single-photon emission computed tomography and DA functionality using pharmacological magnetic resonance imaging, following a dAMPH challenge...
March 13, 2015: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/25337714/investigation-of-cross-species-translatability-of-pharmacological-mri-in-awake-nonhuman-primate-a-buprenorphine-challenge-study
#17
Stephanie Seah, Abu Bakar Ali Asad, Richard Baumgartner, Dai Feng, Donald S Williams, Elaine Manigbas, John D Beaver, Torsten Reese, Brian Henry, Jeffrey L Evelhoch, Chih-Liang Chin
BACKGROUND: Pharmacological MRI (phMRI) is a neuroimaging technique where drug-induced hemodynamic responses can represent a pharmacodynamic biomarker to delineate underlying biological consequences of drug actions. In most preclinical studies, animals are anesthetized during image acquisition to minimize movement. However, it has been demonstrated anesthesia could attenuate basal neuronal activity, which can confound interpretation of drug-induced brain activation patterns. Significant efforts have been made to establish awake imaging in rodents and nonhuman primates (NHP)...
2014: PloS One
https://www.readbyqxmd.com/read/25266821/neuronal-circuitry-underlying-the-impact-of-d3-receptor-ligands-in-drug-addiction
#18
REVIEW
Bernard Le Foll, Patricia Di Ciano
Since the cloning of the D3 receptor in the early 1990s, there has been a great deal of interest in this receptor as a possible therapeutic target for drug addiction. The development of a D3 ligand suitable for use in humans has remained elusive, so the study of the function of the D3 receptor and its possible therapeutic efficacy has largely been restricted to animals. Pre-clinical studies have established that systemic administration of D3 ligands, particularly antagonists and partial agonists, can alter drug-seeking in animals...
September 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/24978048/-application-of-pharmacologic-functional-magnetic-resonance-imaging-phmri-in-the-research-of-affective-disorders
#19
REVIEW
Andrea Edit Édes, Xénia Gonda, György Bagdy, Gabriella Juhász
Many common psychiatric disorders such as depression and anxiety disorders are associated with dysfunction in the monoamine neurotransmission in the central nervous system. However, the investigation of these pathophysiological processes in the human living brain is difficult. In case of functional magnetic resonance imaging (fMRI), a non-invasive method for the examination of brain activity, the activity-inducing stimulus is generally a cognitive psychological test, while during pharmacological magnetic resonance imaging (phMRI) the activation is triggered by a specific pharmacon...
June 2014: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/24643080/vascular-action-as-the-primary-mechanism-of-cognitive-effects-of-cholinergic-cns-acting-drugs-a-rat-phmri-bold-study
#20
Pál Kocsis, István Gyertyán, János Éles, Judit Laszy, Nikolett Hegedűs, Dávid Gajári, Levente Deli, Zsófia Pozsgay, Szabolcs Dávid, Károly Tihanyi
Concordant results of functional magnetic resonance imaging (fMRI) and behavioral tests prove that some non-blood-brain barrier-penetrating drugs produce robust central nervous system (CNS) effects. The anticholinergic scopolamine interferes with learning when tested in rats, which coincides with a negative blood-oxygen-level-dependent (BOLD) change in the prefrontal cortex (PFC) as demonstrated by fMRI. The peripherally acting butylscopolamine also evokes a learning deficit in a water-labyrinth test and provokes a negative BOLD signal in the PFC...
June 2014: Journal of Cerebral Blood Flow and Metabolism
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