Publications by authors named "Abdeslam Chagraoui"

29 Publications

  • Page 1 of 1

Serotonin modulation of hippocampal functions: From anatomy to neurotherapeutics.

Prog Brain Res 2021 10;261:83-158. Epub 2021 Mar 10.

Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, United Kingdom.

The hippocampal region receives a dense serotoninergic innervation originating from both medial and dorsal raphe nuclei. This innervation regulates hippocampal activity through the activation of distinct receptor families that are expressed in excitatory and inhibitory neurons, terminals of several afferent neurotransmitter systems, and glial cells. Preclinical and clinical studies indicate that hippocampal dysfunctions are involved in learning and memory deficits, dementia, Alzheimer's disease, epilepsy and mood disorders such as anxiety, depression and post-traumatic syndrome disorder, whereas the hippocampus participates also in the therapeutic mechanisms of numerous medicines. Not surprisingly, several drugs acting via 5-HT mechanisms are efficacious to some extent in some diseases and the link between 5-HT and the hippocampus although clear remains difficult to untangle. For this reason, we review reported data concerning the distribution and the functional roles of the 5-HT receptors in the hippocampal region in health and disease. The impact of the 5-HT systems on the hippocampal function is such that the research of new 5-HT mechanisms and drugs is still very active. It concerns notably drugs acting at the 5-HT,,, receptor subtypes, in addition to the already existing drugs including the selective serotonin reuptake inhibitors.
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http://dx.doi.org/10.1016/bs.pbr.2021.01.031DOI Listing
March 2021

Multiple facets of serotonergic modulation.

Prog Brain Res 2021 12;261:3-39. Epub 2021 Mar 12.

Centre National de La Recherche Scientifique, Institut des Neurosciences Intégratives et Cognitives d'Aquitaine, UMR 5287, Bordeaux, France.

The serotonergic system of the central nervous system (CNS) has been implicated in a broad range of physiological functions and behaviors, such as cognition, mood, social interaction, sexual behavior, feeding behavior, sleep-wake cycle and thermoregulation. Serotonin (5-hydroxytryptamine, 5-HT) establishes a plethora of interactions with neurochemical systems in the CNS via its numerous 5-HT receptors and autoreceptors. The facets of this control are multiple if we consider the molecular actors playing a role in the autoregulation of 5-HT neuron activity including the 5-HT, 5-HT, 5-HT, 5-HT, 5-HT receptors as well as the serotonin transporter. Moreover, extrinsic loops involving other neurotransmitters giving the other 5-HT receptors the possibility to impact 5-HT neuron activity. Grasping the complexity of these interactions is essential for the development of a variety of therapeutic strategies for cognitive defects and mood disorders. Presently we can illustrate the plurality of the mechanisms and only conceive that these 5-HT controls are likely not uniform in terms of regional and neuronal distribution. Our understanding of the specific expression patterns of these receptors on specific circuits and neuronal populations are progressing and will expand our comprehension of the function and interaction of these receptors with other chemical systems. Thus, the development of new approaches profiling the expression of 5-HT receptors and autoreceptors should reveal additional facets of the 5-HT controls of neurochemical systems in the CNS.
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http://dx.doi.org/10.1016/bs.pbr.2021.02.002DOI Listing
March 2021

Serotonin/dopamine interaction: Electrophysiological and neurochemical evidence.

Prog Brain Res 2021 12;261:161-264. Epub 2021 Mar 12.

Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, Msida, Malta; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, United Kingdom. Electronic address:

The interaction between serotonin (5-HT) and dopamine (DA) in the central nervous system (CNS) plays an important role in the adaptive properties of living animals to their environment. These are two modulatory, divergent systems shaping and regulating in a widespread manner the activity of neurobiological networks and their interaction. The concept of one interaction linking these two systems is rather elusive when looking at the mechanisms triggered by these two systems across the CNS. The great variety of their interacting mechanisms is in part due to the diversity of their neuronal origin, the density of their fibers in a given CNS region, the distinct expression of their numerous receptors in the CNS, the heterogeneity of their intracellular signaling pathway that depend on the cellular type expressing their receptors, and the state of activity of neurobiological networks, conditioning the outcome of their mutual influences. Thus, originally conceptualized as inhibition of 5-HT on DA neuron activity and DA neurotransmission, this interaction is nowadays considered as a multifaceted, mutual influence of these two systems in the regulation of CNS functions. These new ways of understanding this interaction are of utmost importance to envision the consequences of their dysfunctions underlined in several CNS diseases. It is also essential to conceive the mechanism of action of psychotropic drugs directly acting on their function including antipsychotic, antidepressant, antiparkinsonian, and drug of abuse together with the development of therapeutic strategies of Alzheimer's diseases, epilepsy, obsessional compulsive disorders. The 5-HT/DA interaction has a long history from the serendipitous discovery of antidepressants and antipsychotics to the future, rationalized treatments of CNS disorders.
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http://dx.doi.org/10.1016/bs.pbr.2021.02.001DOI Listing
March 2021

Cell-penetrating, antioxidant SELENOT mimetic protects dopaminergic neurons and ameliorates motor dysfunction in Parkinson's disease animal models.

Redox Biol 2021 Apr 28;40:101839. Epub 2020 Dec 28.

UNIROUEN, Inserm U1239, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Rouen Normandie University, 76821, Mont-Saint-Aignan, France; Institute for Research and Innovation in Biomedicine, 76000, Rouen, France. Electronic address:

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor dysfunction for which there is an unmet need for better treatment options. Although oxidative stress is a common feature of neurodegenerative diseases, notably PD, there is currently no efficient therapeutic strategy able to tackle this multi-target pathophysiological process. Based on our previous observations of the potent antioxidant and neuroprotective activity of SELENOT, a vital thioredoxin-like selenoprotein, we designed the small peptide PSELT from its redox active site to evaluate its antioxidant properties in vivo, and its potential polyfunctional activity in PD models. PSELT protects neurotoxin-treated dopaminergic neurons against oxidative stress and cell death, and their fibers against neurotoxic degeneration. PSELT is cell-permeable and acts in multiple subcellular compartments of dopaminergic neurons that are vulnerable to oxidative stress. In rodent models of PD, this protective activity prevented neurodegeneration, restored phosphorylated tyrosine hydroxylase levels, and led to improved motor skills. Transcriptomic analysis revealed that gene regulation by PSELT after MPP treatment negatively correlates with that occurring in PD, and positively correlates with that occurring after resveratrol treatment. Mechanistically, a major impact of PSELT is via nuclear stimulation of the transcription factor EZH2, leading to neuroprotection. Overall, these findings demonstrate the potential of PSELT as a therapeutic candidate for treatment of PD, targeting oxidative stress at multiple intracellular levels.
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http://dx.doi.org/10.1016/j.redox.2020.101839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7823055PMC
April 2021

Editorial: Contemporary Perspective on 5-HT Receptor Function and Its Pharmacological Targeting.

Front Pharmacol 2020 23;11:606414. Epub 2020 Nov 23.

Center for Addiction Research and Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.

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http://dx.doi.org/10.3389/fphar.2020.606414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7724505PMC
November 2020

A Subset of Purposeless Oral Movements Triggered by Dopaminergic Agonists Is Modulated by 5-HT Receptors in Rats: Implication of the Subthalamic Nucleus.

Int J Mol Sci 2020 Nov 12;21(22). Epub 2020 Nov 12.

Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), 146 Rue Léo Saignat, 33076 Bordeaux CEDEX, France.

Dopaminergic medication for Parkinson's disease is associated with troubling dystonia and dyskinesia and, in rodents, dopaminergic agonists likewise induce a variety of orofacial motor responses, certain of which are mimicked by serotonin2C (5-HT) receptor agonists. However, the neural substrates underlying these communalities and their interrelationship remain unclear. In Sprague-Dawley rats, the dopaminergic agonist, apomorphine (0.03-0.3 mg/kg) and the preferential D2/3 receptor agonist quinpirole (0.2-0.5 mg/kg), induced purposeless oral movements (chewing, jaw tremor, tongue darting). The 5-HT receptor antagonist 5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxyl]-5-pyridyl]carbamoyl]-6-trifluoromethylindone (SB 243213) (1 mg/kg) reduced the oral responses elicited by specific doses of both agonists (0.1 mg/kg apomorphine; 0.5 mg/kg quinpirole). After having confirmed that the oral bouts induced by quinpirole 0.5 mg/kg were blocked by another 5-HT antagonist (6-chloro-5-methyl-1-[6-(2-methylpiridin-3-yloxy)pyridine-3-yl carbamoyl] indoline (SB 242084), 1 mg/kg), we mapped the changes in neuronal activity in numerous sub-territories of the basal ganglia using c-Fos expression. We found a marked increase of c-Fos expression in the subthalamic nucleus (STN) in combining quinpirole (0.5 mg/kg) with either SB 243213 or SB 242084. In a parallel set of electrophysiological experiments, the same combination of SB 243213/quinpirole produced an irregular pattern of discharge and an increase in the firing rate of STN neurons. Finally, it was shown that upon the electrical stimulation of the anterior cingulate cortex, quinpirole (0.5 mg/kg) increased the response of substantia nigra pars reticulata neurons corresponding to activation of the "hyperdirect" (cortico-subthalamonigral) pathway. This effect of quinpirole was abolished by the two 5-HT antagonists. Collectively, these results suggest that induction of orofacial motor responses by D2/3 receptor stimulation involves 5-HT receptor-mediated activation of the STN by recruitment of the hyperdirect (cortico-subthalamonigral) pathway.
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http://dx.doi.org/10.3390/ijms21228509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698107PMC
November 2020

Chronic Administration of Fipronil Heterogeneously Alters the Neurochemistry of Monoaminergic Systems in the Rat Brain.

Int J Mol Sci 2020 Aug 9;21(16). Epub 2020 Aug 9.

Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), 146 rue Léo Saignat, B.P.281, F-33000 Bordeaux CEDEX, France.

Fipronil (FPN), a widely used pesticide for agricultural and non-agricultural pest control, is possibly neurotoxic for mammals. Brain monoaminergic systems, involved in virtually all brain functions, have been shown to be sensitive to numerous pesticides. Here, we addressed the hypothesis that chronic exposure to FPN could modify brain monoamine neurochemistry. FPN (10 mg/kg) was chronically administered for 21 days through oral gavage in rats. Thereafter, the tissue concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid; serotonin (5-HT) and its metabolite, 5-hydroxyindoleacetic acid (5-HIAA); and noradrenaline (NA) were measured in 30 distinct brain regions. FPN significantly decreased DA and its metabolite levels in most striatal territories, including the nucleus accumbens and the substantia nigra (SN). FPN also diminished 5-HT levels in some striatal regions and the SN. The indirect index of the turnovers, DOPAC/DA and 5-HIAA/5-HT ratios, was increased in numerous brain regions. FPN reduced the NA content only in the nucleus accumbens core. Using the Bravais-Pearson test to study the neurochemical organization of monoamines through multiple correlative analyses across the brain, we found fewer correlations for NA, DOPAC/DA, and 5-HIAA/5-HT ratios, and an altered pattern of correlations within and between monoamine systems. We therefore conclude that the chronic administration of FPN in rats induces massive and inhomogeneous changes in the DA and 5-HT systems in the brain.
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http://dx.doi.org/10.3390/ijms21165711DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7461054PMC
August 2020

Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain.

Front Pharmacol 2020 30;11:962. Epub 2020 Jun 30.

Centre National de la Recherche Scientifique, UMR CNRS 5287, Bordeaux, France.

Lorcaserin is a preferential serotonin2C receptor (5-HTR) agonist effective to treat obesity that has also recently been proposed to treat addiction and epilepsy. Central dopamine (DA) mechanisms are likely involved in the lorcaserin mechanism of action, but other monoamines 5-HT and noradrenaline (NA) contents or their interaction with DA might account for its effects. Here we showed that lorcaserin at 3, but not 0.3 mg/kg enhanced 5-HT content in the insular cortex, the core of the nucleus accumbens, and ventral hypothalamus. Without affecting the metabolite 5-hydroxy indole acetic acid, lorcaserin reduced the indirect index of 5-HT turnover in the hippocampus, substantia nigra, and habenula. Lorcaserin at 3 mg/kg increased NA content in the orbitofrontal cortex, the central amygdala (also at 0.3 mg/kg), the ventral hypothalamus, and the shell of the nucleus accumbens. A correlative analysis of the tissue contents between pairs of brain regions revealed that 0.3 mg/kg lorcaserin enhanced the number of correlations for 5-HT, its metabolism, and NA to a lower extent. The correlation profiles were very different between saline, 0.3 and 3 mg/kg lorcaserin. Lorcaserin enhanced the correlations established between NA or 5-HT at 0.3 and 3 mg/kg and reduced the number of correlations established between the index of the turnover for DA and 5-HT. These results show that lorcaserin modulates the biochemistry of NA and 5-HT systems in a subset of brain regions. Qualitatively, they reveal, oppositely to the DA changes, that lorcaserin at 0.3, but not 3 mg/kg, enhanced the number of correlations of 5-HT content between brain regions.
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http://dx.doi.org/10.3389/fphar.2020.00962DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7344148PMC
June 2020

Epigenetics and Attention-Deficit/Hyperactivity Disorder: New Perspectives?

Front Psychiatry 2020 17;11:579. Epub 2020 Jun 17.

Department of Child and Adolescent Psychiatry, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.

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http://dx.doi.org/10.3389/fpsyt.2020.00579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7311572PMC
June 2020

[Acute hemolysis crisis revealed a Wilson disease].

Ann Biol Clin (Paris) 2020 08;78(4):425-432

Service d'hématologie biologique, Institut de biologie clinique, CHU-Hôpitaux de Rouen, France.

Wilson disease is a rare inherited disorder of copper metabolism that affects liver and brain due to copper tissue accumulation. The mechanism involved is based on mutations of the ATP7B gene. Children have predominant hepatic manifestations while adult are more often diagnosed by neurological and psychiatric symptoms. However, others features are tubulopathy, articular disorders and hemolytic anemia. We report the diagnostic of Wilson disease in a 14 years old girl and her sibling after investigation of hemolytic anemia, hepatic insufficiency, and hypophosphatemia.
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http://dx.doi.org/10.1684/abc.2020.1574DOI Listing
August 2020

Coronaridine congeners potentiate GABA receptors and induce sedative activity in mice in a benzodiazepine-insensitive manner.

Prog Neuropsychopharmacol Biol Psychiatry 2020 07 16;101:109930. Epub 2020 Mar 16.

Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Normandie University, UNIROUEN, INSERM U1239, Institute for Research and Innovation in Biomedicine of Normandy (IRIB) Rouen, France; Department of Medical Biochemistry, Rouen University Hospital, CHU de Rouen, France. Electronic address:

To determine whether (+)-catharanthine induces sedative- or anxiolytic/anxiogenic-like activity in male mice, proper animal paradigms were used. The results showed that (+)-catharanthine induces sedative-like activity in the 63-72 mg/Kg dose range in a flumazenil-insensitive manner, but neither this effect nor anxiolytic/anxiogenic-like activity was observed at lower doses. To determine the underlying molecular mechanism of the sedative-like activity, electrophysiological and radioligand binding experiments were performed with (+)-catharanthine and (±)-18-methoxycoronaridine [(±)-18-MC] on GABA (GABARs) and glycine receptors (GlyRs). Coronaridine congeners both activated and potentiated a variety of human (h) GABARs, except hρ1. (+)-Catharanthine-induced potentiation followed this receptor selectivity (EC's in μM): hα1β2 (4.6 ± 0.8) > hα2β2γ2 (12.6 ± 3.8) ~ hα1β2γ2 (14.4 ± 4.6) indicating that both α1 and α2 are equally important, whereas γ2 is not necessary. (+)-Catharanthine was >2-fold more potent and efficient than (±)-18-MC at hα1β2γ2. (+)-Catharanthine also potentiated, whereas (±)-18-MC inhibited, hα1 GlyRs with very low potency. Additional [H]-flunitrazepam competition binding experiments using rat cerebellum membranes clearly demonstrated that these ligands do not bind to the benzodiazepine site. This is supported by the observed activity at hα1β2 (lacking the BDZ site) and similar effects between α1- and α2-containing GABARs. Our study shows, for the first time, that (+)-catharanthine induced sedative-like effects in mice, and coronaridine congeners potentiated human α1β2γ2, α1β2, and hα2β2γ2, but not ρ1, GABARs, both in a benzodiazepine-insensitive fashion, whereas only (+)-catharanthine slightly potentiated GlyRs.
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http://dx.doi.org/10.1016/j.pnpbp.2020.109930DOI Listing
July 2020

Constitutive activity of 5-HT receptors: Factual analysis.

Neuropharmacology 2020 05 17;168:107967. Epub 2020 Jan 17.

Laboratory of Neurophysiology, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta, MSD 2080, Msida, Malta; Neuroscience Division, School of Biosciences, Cardiff University, Cardiff, CF10 3AT, UK. Electronic address:

The constitutive activity of different serotonin receptors (5-HTRs) toward intracellular signaling pathways has been proposed to have physiological and pathological importance. Inverse agonists block the constitutive activity and can be used to probe and silence such a spontaneous activity. The constitutive activity of 5-HTRs can be observed in various heterologous systems of expression in vitro (very high for 5-HTR; very low for 5-HTR). The demonstration of the existence of this activity in native tissues and ultimately in integrative neurobiology and behavior is a real pharmacological challenge. Irrespective of the existence of mutants or polymorphisms that could alter the constitutive activity of 5-HTRs, evidence suggests that spontaneous activity of 5-HTR could impact the activity of neurobiological networks and that of 5-HTR and 5-HTR the developmental morphogenesis. Some findings exist for 5-HTR and 5-HTR in diverse though rare conditions. The existence of a constitutive activity for 5-HTR, 5-HTR, and 5-HTR is still poorly supported. When identified, the constitutive activity may differ according to brain location, state of activity (phasic in nature), and intracellular signaling pathways. A very few studies have reported aberrant constitutive activity of 5-HTRs in animal models of human diseases and patients. The purpose of this review is a critical examination of the available neuropharmacological data on the constitutive activity of 5-HTRs to determine whether this activity is an essential component of the serotonergic system transmission and it may be a possible target for CNS drug development.
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http://dx.doi.org/10.1016/j.neuropharm.2020.107967DOI Listing
May 2020

L-DOPA in Parkinson's Disease: Looking at the "False" Neurotransmitters and Their Meaning.

Int J Mol Sci 2019 Dec 31;21(1). Epub 2019 Dec 31.

Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), 33076 Bordeaux CEDEX, France.

-3,4-dihydroxyphenylalanine (L-DOPA) has been successfully used in the treatment of Parkinson's disease (PD) for more than 50 years. It fulfilled the criteria to cross the blood-brain barrier and counteract the biochemical defect of dopamine (DA). It remarkably worked after some adjustments in line with the initial hypothesis, leaving a poor place to the plethora of mechanisms involving other neurotransmitters or mechanisms of action beyond newly synthesized DA itself. Yet, its mechanism of action is far from clear. It involves numerous distinct cell populations and does not mimic the mechanism of action of dopaminergic agonists. L-DOPA-derived DA is mainly released by serotonergic neurons as a false neurotransmitter, and serotonergic neurons are involved in L-DOPA-induced dyskinesia. The brain pattern and magnitude of DA extracellular levels together with this status of false neurotransmitters suggest that the striatal effects of DA via this mechanism would be minimal. Other metabolic products coming from newly formed DA or through the metabolism of L-DOPA itself could be involved. These compounds can be trace amines and derivatives. They could accumulate within the terminals of the remaining monoaminergic neurons. These "false neurotransmitters," also known for some of them as inducing an "amphetamine-like" mechanism, could reduce the content of biogenic amines in terminals of monoaminergic neurons, thereby impairing the exocytotic process of monoamines including L-DOPA-induced DA extracellular outflow. The aim of this review is to present the mechanism of action of L-DOPA with a specific attention to "false neurotransmission."
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http://dx.doi.org/10.3390/ijms21010294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981630PMC
December 2019

Lorcaserin bidirectionally regulates dopaminergic function site-dependently and disrupts dopamine brain area correlations in rats.

Neuropharmacology 2020 04 17;166:107915. Epub 2019 Dec 17.

Neurophysiology Laboratory, Department of Physiology and Biochemistry, Faculty of Medicine and Surgery, University of Malta - Msida, Malta; School of Biosciences, Cardiff University, Cardiff, UK. Electronic address:

Lorcaserin, which is a selective agonist of serotonin2C receptors (5-HTRs), is a new FDA-approved anti-obesity drug that has also shown therapeutic promise in other brain disorders, such as addiction and epilepsy. The modulation of dopaminergic function might be critical in the therapeutic effect of lorcaserin, but its exact effect is unknown. Here, we studied the effect of the peripheral administration of lorcaserin on the ventral tegmental area (VTA), the substantia nigra pars compacta (SNc) dopaminergic neural activity, dopamine (DA) dialysis levels in the nucleus accumbens and striatum and on DA tissue levels in 29 different rat brain regions. Lorcaserin (5-640 μg/kg, i.v.) moderately inhibited only a subpopulation of VTA DA neurons, but had no effect on the SNc neurons. Lorcaserin (0.3, 3 mg/kg, i.p.) did not change VTA and SNc DA population neural activity but slightly decreased the firing rate and burst firing of the spontaneously active VTA neurons, without altering DA extracellular dialysate levels in both the nucleus accumbens and the striatum. Quantitative analysis of DA and metabolites tissue contents of the 29 areas studied revealed that lorcaserin (0.3 or 3 mg/kg, i.p.) only affected a few brain regions, i.e., increased DA in the central amygdala, ventral hypothalamus and nucleus accumbens core and decreased it in the ventromedial striatum. On the other hand, lorcaserin dramatically changed the direction and reduced the number of correlations of DA tissue content among several brain areas. These effects on DA terminal networks might be significant in the therapeutic mechanism of lorcaserin. This article is part of the special issue entitled 'Serotonin Research: Crossing Scales and Boundaries'.
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http://dx.doi.org/10.1016/j.neuropharm.2019.107915DOI Listing
April 2020

Effect of the 5-HT Receptor Agonist WAY-163909 on Serotonin and Dopamine Metabolism across the Rat Brain: A Quantitative and Qualitative Neurochemical Study.

Int J Mol Sci 2019 06 14;20(12). Epub 2019 Jun 14.

Normandie Univ, UNIROUEN, INSERM, U1239, CHU Rouen, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Institute for Research and Innovation in Biomedicine of Normandy (IRIB), 76000 Rouen, France.

The effects triggered by serotonin2C (5-hydroxytryptamin, 5-HT) receptor agonists in the brain are often subtle, and methodologies highlighting their widespread actions to account for their multiple modulatory influences on behaviors are still lacking. We report an extended analysis of a neurochemical database on monoamines obtained after the intraperitoneal administration of the preferential 5-HT receptor agonist WAY-163909 (0.3 and 3 mg/kg) in 29 distinct rat brain regions. We focused on the metabolite of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA), the metabolites of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), and the index of the turnovers 5-HIAA/5-HT and DOPAC/DA. WAY-163909 increased and decreased 5-HIAA tissue levels in the amygdala and dorsolateral orbitofrontal cortex, respectively, and decreased the 5-HT turnover in the infralimbic cortex. It enhanced HVA levels in the medial orbitofrontal cortex and DOPAC levels in the amygdala. WAY-163909 increased and decreased DA turnover in the medial orbitofrontal cortex and the anterior insular cortex, respectively. The correlative analysis of the turnovers between pairs of brain regions revealed low levels of correlations across the brain but presented a distinct pattern of correlations after WAY-163909 was compared to saline-treated rats. WAY-163909, notably at 0.3 mg/kg, favored cortico-cortical and cortico-subcortical correlations of both turnovers separately, and frontal DOPAC/DA ratio with cortical and subcortical 5-HIAA/5-HT ratios at 3 mg/kg. In conclusion, the qualitative, but not the quantitative analysis shows that WAY-163909 alters the pattern of correlations across the brain, which could account for its multiple behavioral influences.
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http://dx.doi.org/10.3390/ijms20122925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627111PMC
June 2019

Early neurochemical modifications of monoaminergic systems in the R6/1 mouse model of Huntington's disease.

Neurochem Int 2019 09 2;128:186-195. Epub 2019 May 2.

Centre National de La Recherche Scientifique-Unité Mixte de Recherche 5287, 33076, Bordeaux Cedex, France. Electronic address:

Huntington's disease (HD) is a rare, autosomal neurodegenerative disease characterized by motor and cognitive impairments appearing in adults. The R6/1 mouse model of the disease recapitulates the adult onset of motor symptoms preceded by cognitive and affective deficits. The monoaminergic systems participate in the establishment of motor and cognitive loops and we postulated that their organization and interaction could be precociously altered. Using tissue measurement of dopamine (DA), serotonin (5-HT), noradrenaline, and some metabolites, we observed that DA and/or its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), but not 5-HT or noradrenaline tissue content was reduced in an age-dependent manner (from two to six months) in the striatum, substantia nigra and globus pallidus of R6/1 mice. The metabolite of 5-HT was also lower in R6/1 mice, mainly in the substantia nigra and hippocampus. We then addressed early disorganization of monoaminergic systems in 18 brain regions encompassing several neurobiological networks in 35 day-old animals. DA tissue content was not altered in the striatum or substantia nigra but was decreased in the nucleus accumbens and increased in the globus pallidus. The correlations of monoaminergic index in-between the 18 selected brain regions revealed distinct organizations of monoamines in R6/1 mice, notably marked by a loss of the number of correlations of the DOPAC/DA ratio. The neurochemical analyses show that each monoaminergic system is distinctly altered in the R6/1 mouse model. The early abnormal organization of these systems likely points out altered maturation of neurobiological networks at early stages of HD.
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http://dx.doi.org/10.1016/j.neuint.2019.05.001DOI Listing
September 2019

Neurochemical impact of the 5-HT receptor agonist WAY-163909 on monoamine tissue content in the rat brain.

Neurochem Int 2019 03 24;124:245-255. Epub 2019 Jan 24.

Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5287, 33076, Bordeaux Cedex, France. Electronic address:

Serotonin2C receptor (5-HT) agonists are promising drugs for the treatment of neuropsychiatric diseases. However, their effect is not completely understood in part because they possibly affect several neurobiological networks simultaneously. We studied the effect of the 5-HT receptor agonist WAY-163909 (0.3 and 3 mg/kg; i.p.) on the tissue concentration of dopamine (DA), 5-HT and noradrenaline (NA) in 29 rat brain regions related to motor, cognitive, mood and vegetative networks. We found that WAY-163909, without altering the tissue concentration of NA, increased 5-HT concentrations in the medial orbitofrontal cortex and the motor cortex M2 at 3 mg/kg and decreased it in the dorsolateral orbitofrontal cortex at 0.3 mg/kg. WAY-163909 enhanced DA concentrations in the central nucleus of the amygdala at 0.3 mg/kg and reduced it in the dorsal hypothalamus at 3 mg/kg. Using correlative analysis of the tissue content of monoamines, WAY-163909 dramatically changed the profile and the pattern of the correlations within and between monoaminergic systems without drastically changing the total number of these correlations. The profile of these changes in correlations was dose-dependent as it was very different between the two doses within and among monoaminergic systems. In conclusion, the data indicated that the 5-HT receptor agonist WAY-163909 quantitatively alters monoamine content in very few regions but promotes multiple changes of monoaminergic connectivity in the brain.
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http://dx.doi.org/10.1016/j.neuint.2019.01.019DOI Listing
March 2019

WFSBP and IAWMH Guidelines for the treatment of alcohol use disorders in pregnant women.

World J Biol Psychiatry 2019 01 11;20(1):17-50. Epub 2019 Jan 11.

k Center for Wellbeing of Women and Mothers, Psychiatry, of Epidemiology (Chronic Diseases) and of Obstetrics, Gynecology, and Reproductive Sciences , Yale University , New Haven , CT , USA.

Objectives: These practice guidelines for the treatment of alcohol use disorders during pregnancy were developed by members of the International Task Force of the World Federation of Societies of Biological Psychiatry and the International Association for Women's Mental Health.

Methods: We performed a systematic review of all available publications and extracted data from national and international guidelines. The Task Force evaluated the data with respect to the strength of evidence for the efficacy and safety of each medication.

Results And Discussion: There is no safe level of alcohol use during pregnancy. Abstinence is recommended. Ideally, women should stop alcohol use when pregnancy is planned and, in any case, as soon as pregnancy is known. Detecting patterns of alcohol maternal drinking should be systematically conducted at first antenatal visit and throughout pregnancy. Brief interventions are recommended in the case of low or moderate risk of alcohol use. Low doses of benzodiazepines, for the shortest duration, may be used to prevent alcohol withdrawal symptoms when high and chronic alcohol intake is stopped and hospitalisation is recommended. Due to the low level of evidence and/or to low benefit/risk ratio, pharmacological treatment for maintenance of abstinence should not be used during pregnancy. At birth, foetal alcohol spectrum disorders must be searched for, and alcohol metabolites should be measured in meconium of neonates in any doubt of foetal alcohol exposure.
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http://dx.doi.org/10.1080/15622975.2018.1510185DOI Listing
January 2019

Reciprocal interaction between monoaminergic systems and the pedunculopontine nucleus: Implication in the mechanism of L-DOPA.

Neurobiol Dis 2019 08 24;128:9-18. Epub 2018 Aug 24.

Centre National de la Recherche Scientifique (Unité Mixte de Recherche 5287), 146 rue Léo Saignat, B.P.281, F-33000 Bordeaux Cedex, France. Electronic address:

The pedunculopontine nucleus (PPN) is part of the mesencephalic locomotor region (MLR) and has been involved in the control of gait, posture, locomotion, sleep, and arousal. It likely participates in some motor and non-motor symptoms of Parkinson's disease and is regularly proposed as a surgical target to ameliorate gait, posture and sleep disorders in Parkinsonian patients. The PPN overlaps with the monoaminergic systems including dopamine, serotonin and noradrenaline in the modulation of the above-mentioned functions. All these systems are involved in Parkinson's disease and the mechanism of the anti-Parkinsonian agents, mostly L-DOPA. This suggests that PPN interacts with monoaminergic neurons and vice versa. Some evidence indicates that the PPN sends cholinergic, glutamatergic and even gabaergic inputs to mesencephalic dopaminergic cells, with the data regarding serotonergic or noradrenergic cells being less well known. Similarly, the control exerted by the PPN on dopaminergic neurons, is multiple and complex, and more extensively explored than the other monoaminergic systems. The data on the influence of monoaminergic systems on PPN neuron activity are rather scarce. While there is evidence that the PPN influences the therapeutic response of L-DOPA, it is still difficult to discerne the reciprocal action of the PPN and monoaminergic systems in this action. Additional data are required to better understand the functional organization of monoaminergic inputs to the MLR including the PPN to get a clearer picture of their interaction.
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http://dx.doi.org/10.1016/j.nbd.2018.08.014DOI Listing
August 2019

Dipotassium ethylenediaminetetraacetic acid is better than tripotassium salt for electrochemiluminescence insulin measurement.

Clin Chim Acta 2016 Dec 29;463:45-46. Epub 2016 Sep 29.

Medical Biochemistry, Rouen University Hospital, Rouen, France, 1 rue de Germont, 76031 Rouen, France. Electronic address:

Previous studies reported that stability of insulin was better on ethylenediaminetetraacetic acid (EDTA) plasma sample than serum sample. However, those studies used tripotassium EDTA (K3-EDTA) tubes, rather than dipotassium EDTA (K2-EDTA) tubes which are more commonly used in laboratories. We investigated the impact of preservative type of EDTA (K2 or K3) on the stability of C-peptide and insulin at 4°C and at room temperature room. Our study has identified that K2-EDTA achieves longer stability of insulin but does not improve the stability of C-peptide. Insulin and C-peptide are stable 24h on the same K2-EDTA sample at room temperature.
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http://dx.doi.org/10.1016/j.cca.2016.09.014DOI Listing
December 2016

Haemoglobin J-Baltimore can be detected by HbA1c electropherogram but with underestimated HbA1c value.

Biochem Med (Zagreb) 2016 ;26(2):240-2

Department of Medical Biochemistry, Rouen University Hospital, Rouen, France; Department of Pharmacology, Rouen University Hospital, Rouen, France.

Glycated haemoglobin (HbA(1c)) is considered the gold standard for assessing diabetes compensation and treatment. In addition, fortuitous detection of haemoglobin variants during HbA1c measurement is not rare. Recently, two publications reported different conclusions on accuracy of HbA(1c) value using capillary electrophoresis method in presence of haemoglobin J-Baltimore (HbJ).
Here we describe the fortuitous detection of unknown HbJ using capillary electrophoresis for measurement of HbA(1c). A patient followed for gestational diabetes in our laboratory presented unknown haemoglobin on Capillarys 2 Flex Piercing analyser which was identified as HbJ. HbJ is not associated with haematological abnormalities. High Performance Liquid Chromatography methods are known to possibly underestimate HbA(1c) value in the presence of this variant. This variant and its glycated form are clearly distinguished on electropherogram but HbJ was responsible for underestimating the true area of HbA(1c).
 Capillary electrophoresis is a good method for detecting HbJ but does not seem suitable for evaluation of HbA(1C) value in patients in presence of HbJ variant.
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http://dx.doi.org/10.11613/BM.2016.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4910267PMC
August 2016

Selenoprotein T Exerts an Essential Oxidoreductase Activity That Protects Dopaminergic Neurons in Mouse Models of Parkinson's Disease.

Antioxid Redox Signal 2016 Apr 16;24(11):557-74. Epub 2016 Mar 16.

1 Inserm U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication , Mont-Saint-Aignan, France .

Aims: Oxidative stress is central to the pathogenesis of Parkinson's disease (PD), but the mechanisms involved in the control of this stress in dopaminergic cells are not fully understood. There is increasing evidence that selenoproteins play a central role in the control of redox homeostasis and cell defense, but the precise contribution of members of this family of proteins during the course of neurodegenerative diseases is still elusive.

Results: We demonstrated first that selenoprotein T (SelT) whose gene disruption is lethal during embryogenesis, exerts a potent oxidoreductase activity. In the SH-SY5Y cell model of dopaminergic neurons, both silencing and overexpression of SelT affected oxidative stress and cell survival. Treatment with PD-inducing neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone triggered SelT expression in the nigrostriatal pathway of wild-type mice, but provoked rapid and severe parkinsonian-like motor defects in conditional brain SelT-deficient mice. This motor impairment was associated with marked oxidative stress and neurodegeneration and decreased tyrosine hydroxylase activity and dopamine levels in the nigrostriatal system. Finally, in PD patients, we report that SelT is tremendously increased in the caudate putamen tissue.

Innovation: These results reveal the activity of a novel selenoprotein enzyme that protects dopaminergic neurons against oxidative stress and prevents early and severe movement impairment in animal models of PD.

Conclusions: Our findings indicate that selenoproteins such as SelT play a crucial role in the protection of dopaminergic neurons against oxidative stress and cell death, providing insight into the molecular underpinnings of this stress in PD.
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http://dx.doi.org/10.1089/ars.2015.6478DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4840926PMC
April 2016

Fortuitous detection of a case of unknown haemoglobin Athens-Georgia from atypical HbA1c electropherogram.

Clin Chim Acta 2015 Feb 5;440:6-7. Epub 2014 Nov 5.

Clinical Biology Institute, Rouen University Hospital-Charles Nicolle, Rouen, France. Electronic address:

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http://dx.doi.org/10.1016/j.cca.2014.10.032DOI Listing
February 2015

The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes.

Endocrinology 2011 Nov 6;152(11):4322-35. Epub 2011 Sep 6.

INSERM, U982, Neuronal and Neuroendocrine Differentiation and Communication Laboratory, Sciences Faculty, University of Rouen, Place Emile Blondel, F-76821 Mont-Saint-Aignan, France.

Selenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues.
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http://dx.doi.org/10.1210/en.2011-1246DOI Listing
November 2011

Structure-affinity relationships of halogenated predicentrine and glaucine derivatives at D1 and D2 dopaminergic receptors: halogenation and D1 receptor selectivity.

Bioorg Med Chem 2005 Jun;13(11):3699-704

Department of Chemistry and Millennium Institute for Advanced Studies in Cell Biology and Biotechnology (CBB), Faculty of Sciences, University of Chile, Casilla 653, Santiago, Chile.

Halogenation of the aporphine alkaloid boldine at the 3-position leads to increased affinity for rat brain D(1)-like dopaminergic receptors with some selectivity over D(2)-like receptors. A series of 3-halogenated and 3,8-dihalogenated (halogen=Cl, Br or I) derivatives of predicentrine (9-O-methylboldine) and glaucine (2,9-di-O-methylboldine) were prepared and assayed for binding at D(1) and D(2) sites. Halogenation of predicentrine led to strong increases in affinity for D(1)-like receptors, while the affinities for D(2)-like receptors were either practically unchanged or reduced three- to fourfold. Halogenated glaucine derivatives did not show any clear trend towards enhanced selectivity, and the affinities were poor and similar to or worse than the values previously recorded for glaucine itself. Together with earlier work on boldine derivatives, these results suggest that the 2-hydroxy group on the aporphine skeleton may determine a binding mode favoring D(1)-like over D(2)-like receptors, with enhanced affinity when the C-3 position is halogenated.
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http://dx.doi.org/10.1016/j.bmc.2005.03.022DOI Listing
June 2005

Long-term heart rate reduction induced by the selective I(f) current inhibitor ivabradine improves left ventricular function and intrinsic myocardial structure in congestive heart failure.

Circulation 2004 Apr 23;109(13):1674-9. Epub 2004 Feb 23.

INSERM U644, UFR de Médecine et de Pharmacie, Rouen, France.

Background: Heart rate reduction (HRR) improves left ventricular (LV) filling, increases myocardial O2 supply, and reduces myocardial O2 consumption, which are all beneficial in congestive heart failure (CHF). However, the long-term effects of HRR on cardiac function and remodeling are unknown.

Methods And Results: We assessed, in rats with CHF, the effects of long-term HRR induced by the selective I(f) current inhibitor ivabradine (as food admix for 90 days starting 7 days after coronary artery ligation). To assess intrinsic modifications of LV tissue induced by long-term HRR, all parameters were reassessed 3 days after interruption of treatment. Ivabradine decreased heart rate over the 90-day treatment period (-18% versus untreated at 10 mg x kg(-1) x d(-1)), without modifying blood pressure, LV end-diastolic pressure, or dP/dt(max/min). Ivabradine significantly reduced LV end-systolic but not end-diastolic diameter, which resulted in preserved cardiac output due to increased stroke volume. In the Langendorff preparation, ivabradine shifted LV systolic but not end-diastolic pressure-volume relations to the left. Ivabradine decreased LV collagen density and increased LV capillary density without modifying LV weight. Three days after interruption of treatment, the effects of ivabradine on LV geometry, shortening, and stroke volume persisted despite normalization of heart rate.

Conclusions: In rats with CHF, long-term HRR induced by the selective I(f) inhibitor ivabradine improves LV function and increases stroke volume, preserving cardiac output despite the HRR. The improvement of cardiac function is related not only to the HRR per se but also to modifications in the extracellular matrix and/or function of myocytes as a consequence of long-term HRR.
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http://dx.doi.org/10.1161/01.CIR.0000118464.48959.1CDOI Listing
April 2004

Agomelatine(S 20098) antagonizes the penile erections induced by the stimulation of 5-HT2C receptors in Wistar rats.

Psychopharmacology (Berl) 2003 Oct 7;170(1):17-22. Epub 2003 Aug 7.

Laboratoire de Physiologie (VACOMED), U.F.R. de Médecine-Pharmacie, 22 Boulevard Gambetta, 76183, Rouen Cedex 1, France.

Agomelatine, an antidepressant with melatonin agonist and 5-HT(2C) antagonist properties, as well as two of its main metabolites, S 21517 (N-[2-(7-hydroxy-1-naphtyl)ethyl]acetamide) and S21540 (N-[2-(3-hydroxy-7-methoxynaphtalen-1-yl)ethyl]acetamide), have been assessed in vitro on pig choroid plexus preparations to determine their affinities for 5-HT(2C) receptors and their effects on inositol phosphate production. These compounds were also tested for their ability to inhibit the penile erections induced by the 5-HT(2C) receptor agonists, m-(chlorophenyl)piperazine (mCPP, 0.75 mg/kg, SC) and Ro 60-0175 (2.5 mg/kg, SC) in Wistar rats. These in vivo effects were compared to those of melatonin and the 5-HT antagonists pizotifen and SB 206,553. Agomelatine and S 21517 had moderate affinity for 5-HT(2C) receptors and behaved in vitro as weak antagonists at this receptor subtype. S 21540 had a 10-fold lower affinity. Pizotifen and SB 206,553 antagonized mCPP- and Ro 60-0175-induced penile erections, suggesting that penile erections induced by mCPP or Ro 60-0175 resulted from the stimulation of 5-HT(2C) receptors. Whereas increasing doses (from 1.25 to 40 mg/kg, IP) of melatonin were unable to modify the penile erections induced by mCPP and Ro 60-0175, agomelatine (from 1.25 to 40 mg/kg, IP) dose-dependently decreased mCPP- as well Ro 60-0175-induced penile erections. Furthermore, increasing doses (from 1.25 to 40 mg/kg, IP) of S 21517 and S 21540, the two main metabolites of agomelatine, did not affect the penile erections induced by mCPP and Ro 60-0175. Considering the similar activity of melatonin and agomelatine at melatonin receptors, these data suggested that the reported effects were not due to the stimulation of melatonin receptors and that, contrary to melatonin, agomelatine exerted 5-HT(2C) receptor antagonist properties in addition to its agonist activity at melatonin receptors. Finally, neither S 21517 nor S 21540 seemed to participate to the observed inhibition of penile erections by agomelatine.
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http://dx.doi.org/10.1007/s00213-003-1465-3DOI Listing
October 2003

Effects of some antioxidative aporphine derivatives on striatal dopaminergic transmission and on MPTP-induced striatal dopamine depletion in B6CBA mice.

Eur J Pharm Sci 2003 Feb;18(2):133-40

Toxicology Laboratory, Faculty of Pharmacy, University of Medicine and Pharmacy, 3400 Cluj-Napoca, Romania.

(S)-(+)-boldine, an aporphine alkaloid displaying antioxidative and dopaminergic properties, and six of its derivatives (glaucine, 3-bromoboldine, 3-iodoboldine, 8-aminoboldine, 8-nitrosoboldine and 2,9-O,O'-dipivaloylboldine) were tested for these properties in comparison with their parent compound. All the tested compounds displayed in vitro antioxidative properties equal to or slightly weaker than those of boldine, and equal to or stronger than (+/-)-6-hydroxy-2,5,7,8,-tetramethylchromane-2-carboxylic acid (Trolox), a water-soluble vitamin E analogue, used as a reference compound. All the aporphine compounds tested displaced [3H]SCH 23390 and [3H]raclopride from their specific binding sites in rat striatum. When tested on dopamine (DA) metabolism in the striatum of B6CBA mice, all the compounds, except 8-aminoboldine, increased striatal levels of DOPAC and HVA, and the HVA/DA ratio, indicating that they cross the blood-brain barrier and that they seem to act as dopamine antagonists in vivo. B6CBA mice were sensitive to the neurotoxic action of MPTP on dopaminergic neurons as indicated by the strongly decreased striatal levels of DA, DOPAC and HVA following administration of MPTP (20 mg/kg, i.p.). Among these aporphine derivatives, only 3-bromoboldine was able to reduce the MPTP-induced decrease of striatal levels of DA and DOPAC, whereas (R)-apomorphine (5 mg/kg, s.c.) and acetylsalicylic acid (100 mg/kg, i.p.), used as reference compounds, were very active. These data suggest that potent in vitro antioxidative properties and the ability to cross the blood-brain barrier are not sufficient criteria to predict the inhibition of neuronal degeneration induced by MPTP.
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http://dx.doi.org/10.1016/s0928-0987(02)00253-1DOI Listing
February 2003

Tissue Doppler imaging differentiates physiological from pathological pressure-overload left ventricular hypertrophy in rats.

Circulation 2002 Apr;105(13):1602-8

INSERM E9920, Rouen University, Rouen, France.

Background: The myocardial velocity gradient (MVG) is a recent index of regional myocardial function derived from endocardial and epicardial velocities obtained by tissue Doppler imaging (TDI). This index might be useful for discriminating between physiological and pathological left ventricular hypertrophy (LVH) and for documenting the early transition from compensated LVH to heart failure. We sought to compare MVG measured across the left ventricular posterior wall between normal rats and rats with physiological (exercise) and pathological (pressure-overload) LVH.

Methods And Results: Wistar rats were assigned to one of the following groups: sedentary, exercise (swimming), and 2-month or 9-month abdominal aortic banding. Compared with sedentary rats, exercise and 2-month banding led to similar and significant LVH. After 2-month banding, conventional parameters of systolic function (left ventricular fractional shortening and dP/dt(max)) were not affected. However, systolic and diastolic MVG were similar in exercise and sedentary rats but were significantly lower in rats with aortic banding. Aortic debanding after 2 months led to a full recovery of MVG, whereas MVG remained decreased when debanding was performed after 9 months.

Conclusions: Myocardial contraction and relaxation assessed by TDI were impaired in pressure-overload LVH but not in exercise LVH. Therefore, TDI is more sensitive than conventional echocardiography for assessing myocardial dysfunction in pressure-overload LVH and for predicting early recovery in myocardial function after loading conditions normalization.
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http://dx.doi.org/10.1161/01.cir.0000012943.91101.d7DOI Listing
April 2002