Sophie Menneson, Yann Serrand, Regis Janvier, Virginie Noirot, Pierre Etienne, Nicolas Coquery, David Val-Laillet
Psychosocial chronic stress is a critical risk factor for the development of mood disorders. However, little is known about the consequences of acute stress in the context of chronic stress, and about the related brain responses. In the present study we examined the physio-behavioural effects of a supplementation with a sensory functional food ingredient (FI) containing Citrus sinensis extract (D11399, Phodé, France) in a pig psychosocial chronic stress model. Female pigs underwent a 5- to 6-week stress protocol while receiving daily the FI (FI, n = 10) or a placebo (Sham, n = 10)...
2020: PloS One
Caterina Montani, Carola Canella, Adam J Schwarz, Jennifer Li, Gary Gilmour, Alberto Galbusera, Keith Wafford, Daniel Gutierrez-Barragan, Andrew McCarthy, David Shaw, Karen Knitowski, David McKinzie, Alessandro Gozzi, Christian Felder
Cholinergic drugs acting at M1/M4 muscarinic receptors hold promise for the treatment of symptoms associated with brain disorders characterized by cognitive impairment, mood disturbances, or psychosis, such as Alzheimer's disease or schizophrenia. However, the brain-wide functional substrates engaged by muscarinic agonists remain poorly understood. Here we used a combination of pharmacological fMRI (phMRI), resting-state fMRI (rsfMRI), and resting-state quantitative EEG (qEEG) to investigate the effects of a behaviorally active dose of the M1/M4-preferring muscarinic agonist xanomeline on brain functional activity in the rodent brain...
December 20, 2020: Neuropsychopharmacology
Yukiko Masaki, Yuto Kashiwagi, Takemi Rokugawa, Miwa Ito, Hitoshi Iimori, Kohji Abe
Pharmacological magnetic resonance imaging (phMRI) allows the visualization of brain pharmacological effects of drugs using functional MRI (fMRI). phMRI can help us facilitate central nervous system (CNS) drug development. However, there have been few studies demonstrating the dose-relationship of the fMRI response induced by CNS drugs to underlying target-engagement or behavioral efficacy. To clarify these relationships, we examined receptor occupancy measurements using positron emission tomography (PET) (n = 3~5), fMRI (n = 5~8) and a cataleptic behavior (n = 6) with raclopride, a dopamine D2 receptor antagonist (8, 20, and 200 μg/kg) on Wistar rats...
July 9, 2020: Synapse
Julie Iven, Jessica R Biesiekierski, Dongxing Zhao, Jan Tack, Lukas Van Oudenhove
Background: Interoceptive properties of food may influence emotional state and its neural basis, as shown for fatty acids but remains unstudied for carbohydrates. Objectives: To study the effects of fructose and its interaction with sad emotion on brain activity in homeostatic and hedonic regions and investigate whether gut hormone responses can explain effects. Design: In 15 healthy subjects, brain activity for 40min after intragastric infusion of fructose (25g) or water was recorded using a cross-over pharmacological magnetic resonance imaging (phMRI) paradigm...
June 19, 2020: Nutritional Neuroscience
Kevin J Black, Haley K Acevedo, Jonathan M Koller
We propose a novel pharmacological fMRI (phMRI) method for objectively quantifying disease severity in Parkinson disease (PD). It is based on the clinical observation that the benefit from a dose of levodopa wears off more quickly as PD progresses. Biologically this has been thought to represent decreased buffering capacity for dopamine as nigrostriatal cells die. Buffering capacity has been modeled based on clinical effects, but clinical measurements are influenced by confounding factors. The new method proposes to measure the effect objectively based on the timing of the known response of several brain regions to exogenous levodopa...
2020: Frontiers in Neurology
Mia Haaranen, Giulia Scuppa, Stefano Tambalo, Vilja Järvi, Sine M Bertozzi, Andrea Armirotti, Wolfgang H Sommer, Angelo Bifone, Petri Hyytiä
The anterior insular cortex plays a key role in the representation of interoceptive effects of drug and natural rewards and their integration with attention, executive function, and emotions, making it a potential target region for intervention to control appetitive behaviors. Here, we investigated the effects of chemogenetic stimulation or inhibition of the anterior insula on alcohol and sucrose consumption. Excitatory or inhibitory designer receptors (DREADDs) were expressed in the anterior insula of alcohol-preferring rats by means of adenovirus-mediated gene transfer...
May 18, 2020: Translational Psychiatry
Maurizio Oggiano, Francesca Zoratto, Gianmauro Palombelli, Fabiana Festucci, Giovanni Laviola, Giuseppe Curcio, Rossella Canese, Walter Adriani
The Naples High Excitability (NHE) is a validated rat strain to model for a mesocortical variant of Attention Deficit Hyperactivity Disorder (ADHD). NHE rats' brains have a tuned-down cortical and a potentiated limbic loop (Zoratto et al. 2017). ADHD and comorbid pathological gambling (PG) involve similar deficits of prefrontal-striatal dialogue. This work aimed to understand if NHE rats (compared to normal random-bred rats, NRB) can be a useful model for gambling vulnerability in ADHD. Experiment 1 evaluated gambling proneness in NHE rats, namely attraction/avoidance in nose-poking for a "Large & Luck-Linked" (LLL) reward (versus a "Small & Sure" one, SS), when the probability of LLL delivery was progressively reduced...
February 8, 2020: Progress in Neuro-psychopharmacology & Biological Psychiatry
Rebecca McMillan, Rachael Sumner, Anna Forsyth, Doug Campbell, Gemma Malpas, Elizabeth Maxwell, Carolyn Deng, John Hay, Rhys Ponton, Frederick Sundram, Suresh Muthukumaraswamy
A single subanaesthetic dose of ketamine rapidly alleviates the symptoms of major depressive disorder (MDD). However, few studies have investigated the acute effects of ketamine on the BOLD pharmacological magnetic resonance imaging (phMRI) response and EEG spectra. In a randomised, double-blind, active placebo-controlled crossover trial, resting-state simultaneous EEG/fMRI was collected during infusion of ketamine or active placebo (remifentanil) in 30 participants with MDD. Montgomery-Asberg depression rating scale scores showed a significant antidepressant effect of ketamine compared to placebo (69% response rate)...
April 20, 2020: Progress in Neuro-psychopharmacology & Biological Psychiatry
Benjamin Vidal, Radu Bolbos, Jérôme Redouté, Jean-Baptiste Langlois, Nicolas Costes, Adrian Newman-Tancredi, Luc Zimmer
The emerging concept of "biased agonism" denotes the phenomenon whereby agonists can preferentially direct receptor signalling to specific intracellular responses among the different transduction pathways, thus potentially avoiding side effects and improving therapeutic effects. The aim of this study was to investigate biased agonism by using pharmacological magnetic resonance imaging (phMRI). The cerebral blood oxygen level dependent (BOLD) signal changes induced by increasing doses of two serotonin 5-HT1A receptor biased agonists, NLX-112 and NLX-101, were mapped in anaesthetized rats...
November 26, 2019: Neuropharmacology
Andrea Edit Edes, Shane McKie, Edina Szabo, Gyongyi Kokonyei, Dorottya Pap, Terezia Zsombok, Mate Magyar, Eva Csepany, Gabor Hullam, Adam Gyorgy Szabo, Lajos Rudolf Kozak, Gyorgy Bagdy, Gabriella Juhasz
BACKGROUND: The anterior cingulate cortex (ACC) is a key structure of the pain processing network. Several structural and functional alterations of this brain area have been found in migraine. In addition, altered serotonergic neurotransmission has been repeatedly implicated in the pathophysiology of migraine, although the exact mechanism is not known. Thus, our aim was to investigate the relationship between acute increase of brain serotonin (5-HT) level and the activation changes of the ACC using pharmacological challenge MRI (phMRI) in migraine patients and healthy controls...
October 15, 2019: BMC Neurology
Andrea Edit Edes, Shane McKie, Edina Szabo, Gyongyi Kokonyei, Dorottya Pap, Terezia Zsombok, Gabor Hullam, Xenia Gonda, Lajos R Kozak, Martyn McFarquhar, Ian M Anderson, J F William Deakin, Gyorgy Bagdy, Gabriella Juhasz
BACKGROUND: The initial effects of selective serotonin reuptake inhibitors (SSRIs) in the human living brain are poorly understood. We carried out a 3T resting state fMRI study with pharmacological challenge to determine the brain activation changes over time following different dosages of citalopram. METHODS: During the study, 7.5 mg i.v. citalopram was administered to 32 healthy subjects. In addition, 11.25 mg citalopram was administered to a subset of 9 subjects to investigate the dose-response...
October 5, 2019: Neuropharmacology
Anouk Schrantee, Michelle M Solleveld, Hilde Schwantje, Willem B Bruin, Henk-Jan Mm Mutsaerts, Sofie M Adriaanse, Paul Lucassen, Jan Booij, Liesbeth Reneman
BACKGROUND: Serotonin transporter blockers, like citalopram, dose-dependently bind to the serotonin transporter. Pharmacological magnetic resonance imaging (phMRI) can be used to non-invasively monitor effects of serotonergic medication. Although previous studies showed that phMRI can measure the effect of a single dose of serotoninergic medication, it is currently unclear whether it can also detect dose-dependent effects. AIMS: To investigate the dose-dependent phMRI response to citalopram and compared this with serotonin transporter occupancy, measured with single photon emission computed tomography (SPECT)...
March 19, 2019: Journal of Psychopharmacology
J E Quintero, Yi Ai, A H Andersen, P Hardy, R Grondin, Z Guduru, D M Gash, G A Gerhardt, Z Zhang
Identification of Parkinson's disease at the earliest possible stage of the disease may provide the best opportunity for the use of disease modifying treatments. However, diagnosing the disease during the pre-symptomatic period remains an unmet goal. To that end, we used pharmacological MRI (phMRI) to assess the function of the cortico-basal ganglia circuit in a non-human primate model of dopamine deficiency to determine the possible relationships between phMRI signals with behavioral, neurochemical, and histological measurements...
February 18, 2019: NeuroImage: Clinical
Stephan Missault, Cynthia Anckaerts, Soumaya Ahmadoun, Ines Blockx, Michaël Barbier, Kenny Bielen, Disha Shah, Samir Kumar-Singh, Winnok H De Vos, Annemie Van der Linden, Stefanie Dedeurwaerdere, Marleen Verhoye
BACKGROUND: Immune activation during pregnancy is an important risk factor for schizophrenia. Brain dysconnectivity and NMDA receptor (NMDAR) hypofunction have been postulated to be central to schizophrenia pathophysiology. The aim of this study was to investigate resting-state functional connectivity (resting-state functional MRI-rsfMRI), microstructure (diffusion tension imaging-DTI) and response to NMDAR antagonist (pharmacological fMRI-phMRI) using multimodal MRI in offspring of pregnant dams exposed to immune challenge (maternal immune activation-MIA model), and determine whether these neuroimaging readouts correlate with schizophrenia-related behaviour...
February 23, 2019: Behavioural Brain Research
Daniel Zaldivar, Alexander Rauch, Nikos K Logothetis, Jozien Goense
Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic resonance imaging (fMRI). Here, we investigated the effects of local injection of ACh on fMRI and neural signals in the primary visual cortex (V1) of anesthetized macaques by combining pharmaco-based MRI (phMRI) with electrophysiological recordings, using single electrodes and electrode arrays...
December 3, 2018: Proceedings of the National Academy of Sciences of the United States of America
A Bifone, A Gozzi, A Cippitelli, A Matzeu, E Domi, H Li, G Scuppa, N Cannella, M Ubaldi, F Weiss, R Ciccocioppo
Alcoholism is often associated with other forms of drug abuse, suggesting that innate predisposing factors may confer vulnerability to addiction to diverse substances. However, the neurobiological bases of these factors remain unknown. Here, we have used a combination of imaging, neurochemistry and behavioral techniques to investigate responses to the psychostimulant amphetamine in Marchigian Sardinian (msP) alcohol-preferring rats, a model of vulnerability to alcoholism. Specifically, we employed pharmacological magnetic resonance imaging to investigate the neural circuits engaged by amphetamine challenge, and to relate functional reactivity to neurochemical and behavioral responses...
October 17, 2018: Addiction Biology
Mitul A Mehta, Anne Schmechtig, Vasileia Kotoula, Juliet McColm, Kimberley Jackson, Claire Brittain, Sitra Tauscher-Wisniewski, Bruce J Kinon, Paul D Morrison, Thomas Pollak, Timothy Mant, Steven C R Williams, Adam J Schwarz
BACKGROUND: Aberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-D-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system...
July 2018: Psychopharmacology
Robert K McNamara, Jennifer D Schurdak, Ruth H Asch, Diana M Lindquist
Although attention deficit hyperactivity disorder is associated with deficits in docosahexaenoic acid (DHA), an omega-3 fatty acid implicated in dopamine and glutamate synaptic plasticity, its role in neuroplastic brain changes that occur following repeated amphetamine (AMPH) treatment are not known. This study used pharmacological magnetic resonance imaging to investigate the impact of repeated AMPH exposure and alterations in brain DHA levels on AMPH-induced brain activation patterns. Male rats were fed a diet with no n-3 fatty acids (Deficient, DEF, n = 20), a diet fortified with preformed DHA (fish oil, FO, n = 20), or a control diet fortified with alpha-linolenic acid (n = 20) from P21 to P90...
December 29, 2017: Nutritional Neuroscience
Rui Zhang, Anders H Andersen, Peter A Hardy, Eric Forman, April Evans, Yi Ai, Jin Yue, Guihua Yue, Don M Gash, Richard Grondin, Zhiming Zhang
Acupuncture has increasingly been used as an alternative therapy for treatment of Parkinson's disease (PD). However, the efficacy of acupunture for PD still remains unclear. The present study was designed to objectively and safely monitor anti-parkinsonian effects of electroacupuncture (EA) and brain activity in nonhuman primates modeling human PD. Six middle-aged rhesus monkeys were extensively studied by a computerized behavioral testing battery and by pharmacological MRI (phMRI) scans with specific dopaminergic drug stimulations...
January 1, 2018: Brain Research
Oliver G Bosch, Fabrizio Esposito, Michael M Havranek, Dario Dornbierer, Robin von Rotz, Philipp Staempfli, Boris B Quednow, Erich Seifritz
Gamma-hydroxybutyrate (GHB) is a GHB-/GABA-B receptor agonist inducing a broad spectrum of subjective effects including euphoria, disinhibition, and enhanced vitality. It is used as treatment for neuropsychiatric disorders including narcolepsy and alcohol withdrawal, but is also a drug of abuse. Non-medical users report enhancement of body and emotion awareness during intoxication. However, the neuronal underpinnings of such awareness alterations under GHB are unknown so far. The assessment of regional cerebral blood flow (rCBF) by pharmacological magnetic resonance imaging (phMRI) enables the elucidation of drug-induced functional brain alterations...
October 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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