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Emmanuel Hermans - One of the best experts on this subject based on the ideXlab platform.
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Involvement of the sigma 1 receptor in the modulation of Dopaminergic Transmission by amantadine.
The European journal of neuroscience, 2004Co-Authors: Magali Peeters, Jean-marie Maloteaux, Pascal Romieu, Tangui Maurice, Emmanuel HermansAbstract:Pharmacological effects of amantadine on Dopaminergic Transmission are proposed to result from an uncompetitive antagonism at glutamate N-methyl-D-aspartate (NMDA) receptors. However, our previous studies examining amantadine-mediated dopamine receptor regulation in the rat striatum revealed a discrepancy from a direct interference with glutamate Transmission. Preliminary in vitro binding data from the literature suggested the interaction of amantadine with the sigma1 receptor. Therefore, we have now further characterized the pharmacological properties of amantadine and memantine at this receptor and investigated its involvement in the modulation of striatal Dopaminergic Transmission. Our binding studies using [3H]-(+)SKF-10,047 indicated that amantadine and memantine behave as ligands of the sigma(1) receptor in rat forebrain homogenates (Ki values of 7.44 +/- 0.82 and 2.60 +/- 0.62 microm, respectively). In NG108-15 neuroblastoma cells, both drugs (amantadine (100 microm) and memantine (10 microm)) potentiated the bradykinin-induced mobilization of intracellular Ca2+, mimicking the effect of the sigma1 receptor agonist PRE-084 (1 microm). Finally, we previously showed that in striatal membranes from amantadine-treated rats, the functional coupling of dopamine receptors with G-proteins was enhanced. Similarly, PRE-084 dose-dependently increased the [35S]GTPgammaS binding induced by dopamine (Emax 28 and 26% of basal, 0.3 and 1 mg/kg PRE-084, respectively). By contrast, BD1047, which is without effect on its own, antagonized the effects of amantadine and PRE-084. Together, these data demonstrate that aminoadamantanes behave as sigma1 receptor agonists, and confirm an involvement of this receptor in modulating dopamine receptors exerted by therapeutically relevant concentrations of amantadine.
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Distinct effects of amantadine and memantine on Dopaminergic Transmission in the rat striatum.
Neuroscience letters, 2003Co-Authors: Magali Peeters, Jean-marie Maloteaux, Emmanuel HermansAbstract:Striatal glutamatergic inputs are known to participate in the modulation of Dopaminergic Transmission. Accordingly, the non-competitive N-methyl-D-aspartate receptor antagonists memantine and amantadine increase striatal dopamine levels, the latter being widely used in Parkinson's disease therapy. Based on our previous work revealing increased function of dopamine receptors and dopamine transporter after amantadine treatment, we studied the effects of repeated memantine administration on Dopaminergic neuroTransmission. On rat striatal membranes, dopamine-stimulated [(35)S]GTPgammaS binding was significantly reduced (20%) after 2 days injection with memantine (20 mg/kg per day, i.p.) but not after longer treatments (4 or 7 days). Evaluation of [(3)H]SCH 23390 and [(3)H]spiperone specific bindings only revealed a significant increase in D1 receptor density after 4 or 7 days treatment. Finally, none of these treatments were found to change the activity of the neuronal dopamine transporter in striatal synaptosomes. This shows that amantadine and memantine differentially affect striatal Dopaminergic Transmission, which could indicate that these two related aminoadamantanes display distinct pharmacodynamic properties.
Pier Vincenzo Piazza - One of the best experts on this subject based on the ideXlab platform.
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Influence of glucocorticoids on Dopaminergic Transmission in the rat dorsolateral striatum.
The European journal of neuroscience, 2001Co-Authors: Michel Barrot, Djoher Nora Abrous, Michela Marinelli, Françoise Rougé-pont, Michel Le Moal, Pier Vincenzo PiazzaAbstract:Glucocorticoid hormones exert strong influences on central neurotransmitter systems. In the present work, we examined the functional consequences of corticosterone suppression on the Dopaminergic Transmission in the dorsolateral striatum by studying the expression of Fos-like proteins and extracellular dopamine levels. Glucocorticoid hormones were suppressed by adrenalectomy, and the specificity of the effects assessed by restoring physiological plasmatic corticosterone concentrations. We show that, in the dorsolateral striatum, glucocorticoids modify postsynaptic Dopaminergic Transmission. Suppression of glucocorticoids decreased the induction of Fos proteins in response to a direct agonist of dopamine D1 receptors (SKF 82958, 1.5 mg/kg, i.p.), but not the release of dopamine induced by morphine (2 mg/kg, s.c.) or the density of the limiting enzyme of dopamine synthesis, tyrosine hydroxylase. In contrast to the Dopaminergic response to morphine, the response to cocaine (15 mg/kg, i.p.) was modified by the suppression of corticosterone. In this case, adrenalectomy increased cocaine-induced changes in extracellular dopamine but did not modify the expression of Fos-like proteins. This absence of changes in cocaine-induced Fos-like proteins might result from a compensatory mechanism between the increase in the Dopaminergic response and the decrease in the functional activity of dopamine D1 receptors. The increased Dopaminergic response to cocaine also contrasts with the decreased response previously observed in the shell of the nucleus accumbens [Barrot et al. (2000) Eur. J. Neurosci., 12, 973–979]. The present data highlight the profound heterogeneous influence of glucocorticoids within Dopaminergic projections.
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Suppression of glucocorticoid secretion and antipsychotic drugs have similar effects on the mesolimbic Dopaminergic Transmission
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Pier Vincenzo Piazza, Michel Barrot, Djoher Nora Abrous, Michela Marinelli, Françoise Rougé-pont, H Simon, Stefania Maccari, Michel Le MoalAbstract:Specific antagonists of central Dopaminergic receptors constitute the major class of antipsychotic drugs (APD). Two principal effects of APD are used as criteria for the pre-clinical screening of their antipsychotic action: ( i ) inhibition of basal and depolarization-induced activity of mesolimbic Dopaminergic neurons; ( ii ) antagonism of the locomotor effects of Dopaminergic agonists. Given that glucocorticoid hormones in animals increase dopamine release and dopamine-mediated behaviors and that high levels of glucocorticoids can induce psychotic symptoms in humans, these experiments examined whether inhibition of endogenous glucocorticoids might have APD-like effects on mesolimbic Dopaminergic Transmission in rats. It is shown that suppression of glucocorticoid secretion by adrenalectomy profoundly decreased (by greater than 50%): ( i ) basal Dopaminergic release and the release of dopamine induced by a depolarizing stimulus such as morphine (2 mg/kg, s.c.), as measured in the nucleus accumbens of freely moving animals by microdialysis; ( ii ) the locomotor activity induced by the direct Dopaminergic agonist apomorphine. The effects of adrenalectomy were glucocorticoid specific given that they were reversed by the administration of glucocorticoids at doses within the physiological range. Despite its profound diminution of Dopaminergic neuroTransmission, adrenalectomy neither modified the number of mesencephalic Dopaminergic neurons nor induced gliosis in the mesencephalon or in the nucleus accumbens, as shown by tyrosine hydroxylase and glial fibrillary acidic protein immunostaining. In conclusion, these findings suggest that blockade of central effects of glucocorticoids might open new therapeutic strategies of behavioral disturbances.
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Glucocorticoids have state-dependent stimulant effects on the mesencephalic Dopaminergic Transmission.
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Pier Vincenzo Piazza, Françoise Rougé-pont, H Simon, Véronique Deroche, Stefania Maccari, M. Le MoalAbstract:Abstract An increase in the activity of mesencephalic Dopaminergic neurons has been implicated in the appearance of pathological behaviors such as psychosis and drug abuse. Several observations suggest that glucocorticoids might contribute to such an increase in Dopaminergic activity. The present experiments therefore analyzed the effects of corticosterone, the major glucocorticoid in the rat, both on dopamine release in the nucleus accumbens of freely moving animals by means of microdialysis, and on locomotor activity, a behavior dependent on accumbens dopamine. Given that glucocorticoids have certain state-dependent neuronal effects, their action on dopamine was studied in situations differing in Dopaminergic tonus, including during the light and dark phases of the circadian cycle, during eating, and in groups of animals differing in their locomotor reactivity to novelty. Dopaminergic activity is increased in the dark period, further increased during food-intake, and is higher in rats defined as high responders to novelty than in low responders. Corticosterone, peripherally administered in a dose that approximates stress-induced plasma concentrations, increased extracellular concentrations of dopamine, and this increase was augmented in the dark phase, during eating, and in high responder rats. Corticosterone had little or no effects in the light phase and in low responder rats. Corticosterone also stimulated locomotor activity, an effect that paralleled the release of dopamine and was abolished by neurochemical (6-hydroxydopamine) depletion of accumbens dopamine. In conclusion, glucocorticoids have state-dependent stimulant effects on mesencephalic Dopaminergic Transmission, and an interaction between these two factors might be involved in the appearance of behavioral disturbances.
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Glucocorticoids havestate-dependent stimulant effects onthe mesencephalic Dopaminergic Transmission
1996Co-Authors: Pier Vincenzo Piazza, Véronique Deroche, Stefania Maccari, Hervei SimonAbstract:Anincrease intheactivity ofmesencephalic Dopaminergic neurons hasbeenimplicated intheappearance ofpathological behaviors suchaspsychosis anddrugabuse. Several observations suggest thatglucocorticoids mightcon- tribute tosuchanincrease inDopaminergic activity. The present experiments therefore analyzed theeffects ofcortico- sterone, themajorglucocorticoid intherat, bothondopamine release inthenucleus accumbens offreely moving animals by meansofmicrodialysis, andonlocomotor activity, abehavior dependent onaccumbens dopamine. Giventhatglucocorti- coidshavecertain state-dependent neuronal effects, their action ondopamine wasstudied insituations differing in Dopaminergic tonus, including during thelight anddark phases ofthecircadian cycle, during eating, andingroups of animals differing intheir locomotor reactivity tonovelty. Dopaminergic activity isincreased inthedarkperiod, further increased during food-intake, andishigher inratsdefined as highresponders tonovelty thaninlowresponders. Cortico- sterone, peripherally administered inadosethatapproxi- matesstress-induced plasma concentrations, increased extra- cellular concentrations ofdopamine, andthisincrease was augmented inthedarkphase, during eating, andinhigh responder rats. Corticosterone hadlittle ornoeffects inthe light phaseandinlowresponder rats. Corticosterone also stimulated locomotor activity, aneffect thatparalleled the release ofdopamine andwasabolished byneurochemical (6-hydroxydopamine) depletion ofaccumbens dopamine. In conclusion, glucocorticoids havestate-dependent stimulant effects onmesencephalic Dopaminergic Transmission, andan interaction between these twofactors might beinvolved inthe appearance ofbehavioral disturbances. Itisgenerally admitted that anincrease intheactivity ofthe mesencephalic Dopaminergic (DA)neurons isrelated tothe appearance ofpathological behaviors. Themajor antipsychotic drugs areantagonists ofDA receptors (1)andprolonged use ofpsychotropic compounds knowntoincrease DA activity can induce psychotic symptoms (2). Furthermore, anenhanced DA activity inthenucleus accumbens isassociated withan increased vulnerability todevelop drugself-administration in laboratory rats(3). Indirect observations suggest that glucocorticoids, thefinal product oftheactivation ofthehypothalamus-pituitary- adrenal axis bystress, might beonefactor capable ofincreasing theactivity ofmesencephalic DA neurons. DA neurons ex- presscorticosteroid receptors (4)anddopamine-mediated behaviors areprofoundly facilitated byglucocorticoids (5). Furthermore, increased glucocorticoid levels caninduce be- havioral changes similar tothose attributed toenhanced DA activity. Inhumans, high levels ofglucocorticoids caninduce
Hans Rommelspacher - One of the best experts on this subject based on the ideXlab platform.
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Influence of Dopaminergic Transmission on severity of withdrawal syndrome in alcoholism.
Journal of Studies on Alcohol and Drugs, 1996Co-Authors: Andreas Heinz, S. Sällström Baum, P. Dufeu, Lutz G. Schmidt, Katrin Schmidt, S Kuhn, Hans RommelspacherAbstract:Objective: Dysfunction of Dopaminergic Transmission has been suggested as influencing withdrawal syndrome in alcohol-dependent patients. Therefore, dopamine levels and sensitivity of dopamine receptors were correlated with the severity of withdrawal syndrome in 40 alcoholics. Method: Dopamine blood plasma levels and apomorphine-induced Growth Hormone (GH) release were measured on the first day of detoxification (Day 1) and after 8 days of abstinence (Day 8). Severity of withdrawal syndrome was assessed daily by the Clinical Institute Withdrawal Assessment (CIWA) score. In the 22 patients (out of the 40) treated by chlormethiazole, severity of withdrawal was measured by the required chlormethiazole dose. Results: A positive correlation was found between dopamine levels on Day 1 and the total CIWA score and necessary chlormethiazole dose, respectively. Correlation with the CIWA score was even stronger when the sensitivity of post-synaptic dopamine receptors was taken into account. No significant correlation...
Laurent Seugnet - One of the best experts on this subject based on the ideXlab platform.
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LAT1-like transporters regulate Dopaminergic Transmission and sleep in Drosophila
SLEEP, 2018Co-Authors: Sami Aboudhiaf, Georges Alves, Sandrine Parrot, Mohamed Amri, Mégane M. Simonnet, Yael Grosjean, Gérard Manière, Laurent SeugnetAbstract:Amino-acid transporters are involved in functions reportedly linked to the sleep/wake cycle: neurotransmitter synthesis and recycling, the regulation of synaptic strength, protein synthesis and energy metabolism. In addition, the existence of bidirectional relationships between extracellular content, transport systems and sleep/wake states is receiving emerging support. Nevertheless, the connection between amino-acid transport and sleep/wake regulation remains elusive. To address this question, we used Drosophilamelanogaster and investigated the role of LAT1 (Large neutral Amino-acid Transporter 1) transporters. We show that the two Drosophila LAT1-like transporters: JhI-21 and minidiscs (Mnd) are required in Dopaminergic neurons for sleep/wake regulation. Down-regulating either gene in Dopaminergic neurons resulted in higher daily sleep and longer sleep bout duration during the night, suggesting a defect in Dopaminergic Transmission. Since LAT1 transporters can mediate in mammals the uptake of L-DOPA, a precursor of dopamine, we assessed amino-acid transport efficiency by L-DOPA feeding. We find that downregulation of JhI-21, but not Mnd, reduced the sensitivity to L-DOPA as measured by sleep loss. JhI-21 downregulation also attenuated the sleep loss induced by continuous activation of Dopaminergic neurons. Since LAT1 transporters are known to regulate TOR (Target Of Rapamycin) signaling, we investigated the role of this amino-acid sensing pathway in Dopaminergic neurons. Consistently, we report that TOR activity in Dopaminergic neurons modulates sleep/wake states. Altogether, this study provides evidence that LAT1 mediated amino-acid transport in Dopaminergic neurons, is playing a significant role in sleep/wake regulation, and is providing several entry points to elucidate the role of nutrients such as amino-acids in sleep/wake regulation.
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LAT1-like transporters regulate Dopaminergic Transmission and sleep in Drosophila
Sleep, 2018Co-Authors: Sami Aboudhiaf, Georges Alves, Sandrine Parrot, Mohamed Amri, Mégane M. Simonnet, Yael Grosjean, Gérard Manière, Laurent SeugnetAbstract:Amino acid transporters are involved in functions reportedly linked to the sleep/wake cycle: neurotransmitter synthesis and recycling, the regulation of synaptic strength, protein synthesis, and energy metabolism. In addition, the existence of bidirectional relationships among extracellular content, transport systems, and sleep/wake states is receiving emerging support. Nevertheless, the connection between amino acid transport and sleep/wake regulation remains elusive. To address this question, we used Drosophila melanogaster and investigated the role of LAT1 (large neutral amino acid transporter 1) transporters. We show that the two Drosophila LAT1-like transporters: Juvenile hormone Inducible-21 and minidiscs (Mnd) are required in Dopaminergic neurons for sleep/wake regulation. Down-regulating either gene in Dopaminergic neurons resulted in higher daily sleep and longer sleep bout duration during the night, suggesting a defect in Dopaminergic Transmission. Since LAT1 transporters can mediate in mammals the uptake of L-DOPA, a precursor of dopamine, we assessed amino acid transport efficiency by L-DOPA feeding. We find that downregulation of JhI-21, but not Mnd, reduced the sensitivity to L-DOPA as measured by sleep loss. JhI-21 downregulation also attenuated the sleep loss induced by continuous activation of Dopaminergic neurons. Since LAT1 transporters are known to regulate target of rapamycin (TOR) signaling, we investigated the role of this amino acid sensing pathway in Dopaminergic neurons. Consistently, we report that TOR activity in Dopaminergic neurons modulates sleep/wake states. Altogether, this study provides evidence that LAT1-mediated amino acid transport in Dopaminergic neurons is playing a significant role in sleep/wake regulation and is providing several entry points to elucidate the role of nutrients such as amino acids in sleep/wake regulation.
Michela Marinelli - One of the best experts on this subject based on the ideXlab platform.
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Dopaminergic Reward Pathways and Effects of Stress
Stress and Addiction, 2007Co-Authors: Michela MarinelliAbstract:Publisher Summary This chapter reviews literature on the dopamine reward system, how it is affected by stress, and its relevance to addiction. It provides a brief definition of stress and an introduction on the dopamine system, including methods used to evaluate its activity. The role of the dopamine system in drug addiction is described and the effects of addictive drugs on different aspects of Dopaminergic Transmission, such as dopamine overflow and action potential output are examined. Furthermore, the chapter discusses the effects of stress on Dopaminergic Transmission and highlights how stress has an inverted-U-shaped effect: Mild/moderate stressors increase Dopaminergic Transmission, whereas intense unpredictable stressors can decrease it. Possible mechanisms underlying the effects of stress on the dopamine system, including the important role of glucocorticoid stress hormones, are also discussed. The review concludes by examining how an interaction between stress and dopamine could play an important role in the development of addiction-associated behaviors.
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Influence of glucocorticoids on Dopaminergic Transmission in the rat dorsolateral striatum.
The European journal of neuroscience, 2001Co-Authors: Michel Barrot, Djoher Nora Abrous, Michela Marinelli, Françoise Rougé-pont, Michel Le Moal, Pier Vincenzo PiazzaAbstract:Glucocorticoid hormones exert strong influences on central neurotransmitter systems. In the present work, we examined the functional consequences of corticosterone suppression on the Dopaminergic Transmission in the dorsolateral striatum by studying the expression of Fos-like proteins and extracellular dopamine levels. Glucocorticoid hormones were suppressed by adrenalectomy, and the specificity of the effects assessed by restoring physiological plasmatic corticosterone concentrations. We show that, in the dorsolateral striatum, glucocorticoids modify postsynaptic Dopaminergic Transmission. Suppression of glucocorticoids decreased the induction of Fos proteins in response to a direct agonist of dopamine D1 receptors (SKF 82958, 1.5 mg/kg, i.p.), but not the release of dopamine induced by morphine (2 mg/kg, s.c.) or the density of the limiting enzyme of dopamine synthesis, tyrosine hydroxylase. In contrast to the Dopaminergic response to morphine, the response to cocaine (15 mg/kg, i.p.) was modified by the suppression of corticosterone. In this case, adrenalectomy increased cocaine-induced changes in extracellular dopamine but did not modify the expression of Fos-like proteins. This absence of changes in cocaine-induced Fos-like proteins might result from a compensatory mechanism between the increase in the Dopaminergic response and the decrease in the functional activity of dopamine D1 receptors. The increased Dopaminergic response to cocaine also contrasts with the decreased response previously observed in the shell of the nucleus accumbens [Barrot et al. (2000) Eur. J. Neurosci., 12, 973–979]. The present data highlight the profound heterogeneous influence of glucocorticoids within Dopaminergic projections.
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Suppression of glucocorticoid secretion and antipsychotic drugs have similar effects on the mesolimbic Dopaminergic Transmission
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Pier Vincenzo Piazza, Michel Barrot, Djoher Nora Abrous, Michela Marinelli, Françoise Rougé-pont, H Simon, Stefania Maccari, Michel Le MoalAbstract:Specific antagonists of central Dopaminergic receptors constitute the major class of antipsychotic drugs (APD). Two principal effects of APD are used as criteria for the pre-clinical screening of their antipsychotic action: ( i ) inhibition of basal and depolarization-induced activity of mesolimbic Dopaminergic neurons; ( ii ) antagonism of the locomotor effects of Dopaminergic agonists. Given that glucocorticoid hormones in animals increase dopamine release and dopamine-mediated behaviors and that high levels of glucocorticoids can induce psychotic symptoms in humans, these experiments examined whether inhibition of endogenous glucocorticoids might have APD-like effects on mesolimbic Dopaminergic Transmission in rats. It is shown that suppression of glucocorticoid secretion by adrenalectomy profoundly decreased (by greater than 50%): ( i ) basal Dopaminergic release and the release of dopamine induced by a depolarizing stimulus such as morphine (2 mg/kg, s.c.), as measured in the nucleus accumbens of freely moving animals by microdialysis; ( ii ) the locomotor activity induced by the direct Dopaminergic agonist apomorphine. The effects of adrenalectomy were glucocorticoid specific given that they were reversed by the administration of glucocorticoids at doses within the physiological range. Despite its profound diminution of Dopaminergic neuroTransmission, adrenalectomy neither modified the number of mesencephalic Dopaminergic neurons nor induced gliosis in the mesencephalon or in the nucleus accumbens, as shown by tyrosine hydroxylase and glial fibrillary acidic protein immunostaining. In conclusion, these findings suggest that blockade of central effects of glucocorticoids might open new therapeutic strategies of behavioral disturbances.