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Toshio Matsuda - One of the best experts on this subject based on the ideXlab platform.
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atomoxetine induced increases in Monoamine Release in the prefrontal cortex are similar in spontaneously hypertensive rats and wistar kyoto rats
Neurochemical Research, 2014Co-Authors: Yukio Ago, Masato Umehara, Kazumi Fujita, Kazuhiro Takuma, Toshio Matsuda, Kosuke Higashino, Shigeru HasebeAbstract:Spontaneously hypertensive rats (SHRs) are used as a model for attention-deficit/hyperactivity disorder (ADHD), since SHRs are hyperactive and show defective sustained attention in behavioral tasks. The psychostimulants amphetamine and methylphenidate and the selective norepinephrine reuptake inhibitor atomoxetine are used as ADHD medications. The effects of high K+ stimulation or psychostimulants on brain norepinephrine or dopamine Release in SHRs have been previously studied both in vitro and in vivo, but the effects of atomoxetine on these neurotransmitters have not. The present study examined the effects of administration of atomoxetine on extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex of juvenile SHRs and Wistar-Kyoto (WKY) rats. Baseline levels of prefrontal norepinephrine, dopamine, and serotonin were similar in SHRs and WKY rats. Systemic administration of atomoxetine (3 mg/kg) induced similar increases in prefrontal norepinephrine and dopamine, but not serotonin, levels in both strains. Furthermore, there was no difference in high K+-induced increases in extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex between SHRs and WKY rats. These findings indicate that Monoamine systems in the prefrontal cortex are similar between SHRs and WKY rats.
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effects of serotonin norepinephrine reuptake inhibitors on locomotion and prefrontal Monoamine Release in spontaneously hypertensive rats
European Journal of Pharmacology, 2013Co-Authors: Masato Umehara, Kazumi Fujita, Naoki Hiramatsu, Kazuhiro Takuma, Toshio MatsudaAbstract:Abstract Catecholamine neurotransmission in the prefrontal cortex plays a key role in the therapeutic actions of drugs for attention-deficit/hyperactivity disorder (ADHD). Recent clinical studies show that several serotonin–norepinephrine reuptake inhibitors have potential for treating ADHD. In this study, we examined the effects of acute treatment with serotonin–norepinephrine reuptake inhibitors on locomotion and the extracellular levels of Monoamines in the prefrontal cortex in spontaneously hypertensive rats (SHR), an animal model of ADHD. Adolescent male SHR exhibited greater horizontal locomotion in an open-field test than male WKY control rats. Psychostimulant methylphenidate (0.3 and 1 mg/kg), the selective norepinephrine reuptake inhibitor atomoxetine (1 and 3 mg/kg), and serotonin–norepinephrine reuptake inhibitors duloxetine (10 mg/kg), venlafaxine (10 and 30 mg/kg) and milnacipran (30 mg/kg) reduced the horizontal activity in SHR, but did not affect in WKY rats. The selective norepinephrine reuptake inhibitor reboxetine (10 mg/kg) and the tricyclic antidepressant desipramine (10 and 30 mg/kg) also reduced the horizontal activity in SHR, whereas the selective serotonin reuptake inhibitor citalopram (30 mg/kg) did not. Microdialysis studies showed that atomoxetine, methylphenidate, duloxetine, venlafaxine, milnacipran, and reboxetine increased the extracellular levels of norepinephrine and dopamine in the prefrontal cortex in SHR. Citalopram did not affect norepinephrine and dopamine levels in the prefrontal cortex, although it increased the serotonin levels. Neither duloxetine nor venlafaxine increased the dopamine levels in the striatum. These findings suggest that serotonin–norepinephrine reuptake inhibitors, similar to methylphenidate and atomoxetine, have potential for ameliorating motor abnormality in the SHR model.
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lithium attenuates methamphetamine induced hyperlocomotion and behavioral sensitization via modulation of prefrontal Monoamine Release
Neuropharmacology, 2012Co-Authors: Yukio Ago, Kazuhiro Takuma, Toshio Matsuda, Tatsunori Tanaka, Yuki Kita, Hokuto TokumotoAbstract:Lithium attenuates psychostimulant-induced hyperactivity and behavioral sensitization, but the exact mechanisms are not known. Previous studies show that lithium has neuromodulatory effects on Monoamine systems. The present study was aimed to clarify whether prefrontal Monoaminergic neurotransmission is involved in the effect of lithium on methamphetamine (METH)-induced behaviors in mice. Lithium attenuated METH-induced hyperactivity and METH-induced increase in extracellular dopamine (DA), but not serotonin (5-HT), levels in the prefrontal cortex. Chronic METH caused behavioral sensitization and enhancement of METH-induced increase in prefrontal 5-HT Release (neurochemical sensitization). Co-administration of lithium with METH attenuated behavioral sensitization and neurochemical sensitization. Chronic METH also reduced the 5-HT(1A) receptor agonist osemozotan-induced decrease in prefrontal 5-HT Release (desensitization of presynaptic 5-HT(1A) autoreceptor), and this effect was reversed by co-administration of lithium. These results suggest that lithium attenuates acute METH-induced hyperactivity and chronic METH-induced behavioral sensitization via modulation of prefrontal Release of DA and 5-HT, respectively. The present study also suggests that a 5-HT(1A) receptor-mediated mechanism is involved in the effect of lithium on chronic METH-induced behavioral sensitization.
Damiaan Denys - One of the best experts on this subject based on the ideXlab platform.
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the 5 ht1a 1b receptor agonist eltoprazine increases both catecholamine Release in the prefrontal cortex and dopamine Release in the nucleus accumbens and decreases motivation for reward and waiting impulsivity but increases stopping impulsivity
European Journal of Pharmacology, 2017Co-Authors: Jolanda Prins, Koen G C Westphal, Gerdien A H Kortebouws, Berend Olivier, Mechiel S Korte, Filip S Van Den Bergh, Ronald S Oosting, Rudy Dupree, Damiaan DenysAbstract:The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects Monoamine Release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the Monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE Release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT Release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT1A/1B-receptor activation decreases impulsive choice, but increases impulsive action.
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unilateral deep brain stimulation in the nucleus accumbens core does not affect local Monoamine Release
Journal of Neuroscience Methods, 2011Co-Authors: Addy Van Dijk, Oliver Mason, Andre A Klompmakers, M G P Feenstra, Damiaan DenysAbstract:Abstract Recent publications have shown promising results of deep brain stimulation (DBS) in the nucleus accumbens for patients with obsessive compulsive disorder and major depressive disorder. Despite its increasing application in the clinical setting, the neurobiological mechanism of action of DBS is still uncertain. One of the possible effects of DBS might be phasic or tonic changes in Monoamine Release either locally in the target area or in a distant, connected region. In the present study we investigate whether unilateral DBS of the Nucleus Accumbens Core (NAc core) has a local effect on in vivo Monoamine Release. Freely moving animals were unilaterally stimulated with 300 μA or 400 μA (120 Hz, pulse width 80 μs) in the NAc core for 5 h. 1 h before and during stimulation we measured dopamine, serotonin, their metabolites and noradrenaline using in vivo microdialysis. We found no significant effect of stimulation on extracellular concentrations of Monoaminergic neurotransmitters or their metabolites in the NAc core during stimulation. Our results suggest that the rapid effects of DBS in the NAc are not a result of changes in local Monoamine Release in the NAc core. For future directions it is interesting to note that several microdialysis and electrophysiology studies have shown effects of DBS in areas distant from the stimulation target.
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the putative antidepressant dov 216 303 a triple reuptake inhibitor increases Monoamine Release in the prefrontal cortex of olfactory bulbectomized rats
European Journal of Pharmacology, 2010Co-Authors: Jolanda Prins, Damiaan Denys, Koen G C Westphal, Gerdien A H Kortebouws, Maria S Quinton, R Schreiber, Lucianne Groenink, Berend Olivier, Mechiel S KorteAbstract:Abstract The first line of antidepressant treatment nowadays are selective serotonin reuptake inhibitors. Although they are relatively safe to use, selective serotonin reuptake inhibitors (SSRIs) can induce severe side effects. New promising antidepressants may be the triple Monoamine reuptake inhibitors, which not only enhance serotonin and norepinephrine neurotransmission, but also increase brain dopamine levels. Recently it has been shown that one of the triple reuptake inhibitors, DOV 216,303 has antidepressant-like effects in the olfactory bulbectomy (OBX) model of depression, but the alterations in Monoaminergic neurotransmission in these animals are still unknown. In the present study we investigated not only the effect of acute, but also chronic treatment of DOV 216,303 in OBX rats on Monoamine and metabolite levels. The main results are decreased baseline dopamine levels in the prefrontal cortex one day after OBX, while 38 days after OBX no difference could be observed in Monoamine levels after vehicle treatment. Treatment with DOV 216,303 leads to increased extracellular levels of serotonin and norepinephrine neurotransmission, but also increased dopamine levels in OBX animals as well as their controls. This increase could be observed after one single administration, but also after chronic treatment. However, a DOV 216,303 challenge in chronically treated animals resulted in lower Monoamine concentrations than the same challenge in untreated animals. More research is needed to investigate this seemingly hyporesponsivity to chronic DOV 216,303 treatment.
Matthias E Liechti - One of the best experts on this subject based on the ideXlab platform.
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pharmacological profile of mephedrone analogs and related new psychoactive substances
Neuropharmacology, 2017Co-Authors: Dino Luethi, Karolina E Kolaczynska, Luca Docci, Stephan Krahenbuhl, Marius C. Hoener, Matthias E LiechtiAbstract:Abstract Background Mephedrone is a synthetic cathinone and one of the most popular recreationally used new psychoactive substances. The aim of the present study was to characterize the in vitro pharmacology of novel analogs of mephedrone and related newly emerged designer stimulants. Methods We determined norepinephrine, dopamine, and serotonin transporter inhibition potencies and Monoamine Release in transporter-transfected human embryonic kidney 293 cells. We also assessed Monoamine receptor and transporter binding affinities. Results Mephedrone analogs potently inhibited the norepinephrine transporter and, with the exception of 3-methylmethcathinone (3-MMC), inhibited the serotonin transporter more potently than the dopamine transporter. Similar to classic amphetamines, mephedrone analogs were substrate-type Monoamine Releasers. 5-(2-Aminopropyl)indole (5-IT) was a highly potent Monoamine transporter inhibitor and a Releaser of dopamine and serotonin. 4-Methylamphetamine (4-MA) mediated efflux of all three Monoamines and inhibited the serotonin transporter more potently than the dopamine transporter, unlike amphetamine. N-methyl-2-aminoindane (N-methyl-2-AI) was a selective norepinephrine transporter inhibitor and norepinephrine Releaser, whereas 5-methoxy-6-methyl-2-aminoindane (MMAI) was a selective serotonin transporter inhibitor and serotonin Releaser. All of the drugs interacted with Monoamine receptors. Conclusion The predominant actions on serotonin vs. dopamine transporters suggest that dimethylmethcathinones, 4-MA, and MMAI cause entactogenic effects similar to 3,4-methylenedioxymethamphetamine, whereas 3-MMC, 5-IT, and N-methyl-2-AI have more stimulant-type properties like amphetamine. Because of pharmacological and structural similarity to mephedrone, similar health risks can be expected for these analogs. This article is part of the Special Issue entitled ‘Designer Drugs and Legal Highs.’
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Monoamine transporter and receptor interaction profiles of a new series of designer cathinones.
Neuropharmacology, 2013Co-Authors: Linda D. Simmler, Anna Rickli, Marius C. Hoener, Matthias E LiechtiAbstract:Abstract Psychoactive β-keto amphetamines (cathinones) are sold as “bath salts” or “legal highs” and recreationally abused. We characterized the pharmacology of a new series of cathinones, including methedrone, 4-methylethcathinone (4-MEC), 3-fluoromethcathinone (3-FMC), pentylone, ethcathinone, buphedrone, pentedrone, and N,N-dimethylcathinone. We investigated norepinephrine (NE), dopamine (DA), and serotonin (5-HT) uptake inhibition using human embryonic kidney 293 (HEK 293) cells that express the respective human Monoamine transporter, the drug-induced efflux of NE, DA, and 5-HT from Monoamine-preloaded cells, and binding affinity to Monoamine transporters and receptors. All of the cathinones were potent NE uptake inhibitors but differed in their DA vs. 5-HT transporter inhibition profiles and Monoamine Release effects. Methedrone was a more potent 5-HT than DA transporter inhibitor and Released NE and 5-HT similar to para-methoxymethamphetamine (PMMA), para-methoxyamphetamine (PMA), 4-methylthioamphetamine (4-MTA), and 3,4-methylenedioxymethamphetamine (MDMA). 4-MEC and pentylone equipotently inhibited all of the Monoamine transporters and Released 5-HT. Ethcathinone and 3-FMC inhibited NE and DA uptake and Released NE, and 3-FMC also Released DA similar to N-ethylamphetamine and methamphetamine. Pentedrone and N,N-dimethylcathinone were non-releasing NE and DA uptake inhibitors as previously shown for pyrovalerone cathinones. Buphedrone preferentially inhibited NE and DA uptake and also Released NE. None of the cathinones bound to rodent trace amine-associated receptor 1, in contrast to the non-β-keto-amphetamines. None of the cathinones exhibited relevant binding to other Monoamine receptors. In summary, we found considerable differences in the Monoamine transporter interaction profiles among different cathinones and compared with related amphetamines.
Mechiel S Korte - One of the best experts on this subject based on the ideXlab platform.
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the 5 ht1a 1b receptor agonist eltoprazine increases both catecholamine Release in the prefrontal cortex and dopamine Release in the nucleus accumbens and decreases motivation for reward and waiting impulsivity but increases stopping impulsivity
European Journal of Pharmacology, 2017Co-Authors: Jolanda Prins, Koen G C Westphal, Gerdien A H Kortebouws, Berend Olivier, Mechiel S Korte, Filip S Van Den Bergh, Ronald S Oosting, Rudy Dupree, Damiaan DenysAbstract:The 5-HT1A/1B-receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects Monoamine Release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the Monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE Release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT Release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT1A/1B-receptor activation decreases impulsive choice, but increases impulsive action.
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the putative antidepressant dov 216 303 a triple reuptake inhibitor increases Monoamine Release in the prefrontal cortex of olfactory bulbectomized rats
European Journal of Pharmacology, 2010Co-Authors: Jolanda Prins, Damiaan Denys, Koen G C Westphal, Gerdien A H Kortebouws, Maria S Quinton, R Schreiber, Lucianne Groenink, Berend Olivier, Mechiel S KorteAbstract:Abstract The first line of antidepressant treatment nowadays are selective serotonin reuptake inhibitors. Although they are relatively safe to use, selective serotonin reuptake inhibitors (SSRIs) can induce severe side effects. New promising antidepressants may be the triple Monoamine reuptake inhibitors, which not only enhance serotonin and norepinephrine neurotransmission, but also increase brain dopamine levels. Recently it has been shown that one of the triple reuptake inhibitors, DOV 216,303 has antidepressant-like effects in the olfactory bulbectomy (OBX) model of depression, but the alterations in Monoaminergic neurotransmission in these animals are still unknown. In the present study we investigated not only the effect of acute, but also chronic treatment of DOV 216,303 in OBX rats on Monoamine and metabolite levels. The main results are decreased baseline dopamine levels in the prefrontal cortex one day after OBX, while 38 days after OBX no difference could be observed in Monoamine levels after vehicle treatment. Treatment with DOV 216,303 leads to increased extracellular levels of serotonin and norepinephrine neurotransmission, but also increased dopamine levels in OBX animals as well as their controls. This increase could be observed after one single administration, but also after chronic treatment. However, a DOV 216,303 challenge in chronically treated animals resulted in lower Monoamine concentrations than the same challenge in untreated animals. More research is needed to investigate this seemingly hyporesponsivity to chronic DOV 216,303 treatment.
Kazuhiro Takuma - One of the best experts on this subject based on the ideXlab platform.
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atomoxetine induced increases in Monoamine Release in the prefrontal cortex are similar in spontaneously hypertensive rats and wistar kyoto rats
Neurochemical Research, 2014Co-Authors: Yukio Ago, Masato Umehara, Kazumi Fujita, Kazuhiro Takuma, Toshio Matsuda, Kosuke Higashino, Shigeru HasebeAbstract:Spontaneously hypertensive rats (SHRs) are used as a model for attention-deficit/hyperactivity disorder (ADHD), since SHRs are hyperactive and show defective sustained attention in behavioral tasks. The psychostimulants amphetamine and methylphenidate and the selective norepinephrine reuptake inhibitor atomoxetine are used as ADHD medications. The effects of high K+ stimulation or psychostimulants on brain norepinephrine or dopamine Release in SHRs have been previously studied both in vitro and in vivo, but the effects of atomoxetine on these neurotransmitters have not. The present study examined the effects of administration of atomoxetine on extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex of juvenile SHRs and Wistar-Kyoto (WKY) rats. Baseline levels of prefrontal norepinephrine, dopamine, and serotonin were similar in SHRs and WKY rats. Systemic administration of atomoxetine (3 mg/kg) induced similar increases in prefrontal norepinephrine and dopamine, but not serotonin, levels in both strains. Furthermore, there was no difference in high K+-induced increases in extracellular norepinephrine, dopamine, and serotonin levels in the prefrontal cortex between SHRs and WKY rats. These findings indicate that Monoamine systems in the prefrontal cortex are similar between SHRs and WKY rats.
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effects of serotonin norepinephrine reuptake inhibitors on locomotion and prefrontal Monoamine Release in spontaneously hypertensive rats
European Journal of Pharmacology, 2013Co-Authors: Masato Umehara, Kazumi Fujita, Naoki Hiramatsu, Kazuhiro Takuma, Toshio MatsudaAbstract:Abstract Catecholamine neurotransmission in the prefrontal cortex plays a key role in the therapeutic actions of drugs for attention-deficit/hyperactivity disorder (ADHD). Recent clinical studies show that several serotonin–norepinephrine reuptake inhibitors have potential for treating ADHD. In this study, we examined the effects of acute treatment with serotonin–norepinephrine reuptake inhibitors on locomotion and the extracellular levels of Monoamines in the prefrontal cortex in spontaneously hypertensive rats (SHR), an animal model of ADHD. Adolescent male SHR exhibited greater horizontal locomotion in an open-field test than male WKY control rats. Psychostimulant methylphenidate (0.3 and 1 mg/kg), the selective norepinephrine reuptake inhibitor atomoxetine (1 and 3 mg/kg), and serotonin–norepinephrine reuptake inhibitors duloxetine (10 mg/kg), venlafaxine (10 and 30 mg/kg) and milnacipran (30 mg/kg) reduced the horizontal activity in SHR, but did not affect in WKY rats. The selective norepinephrine reuptake inhibitor reboxetine (10 mg/kg) and the tricyclic antidepressant desipramine (10 and 30 mg/kg) also reduced the horizontal activity in SHR, whereas the selective serotonin reuptake inhibitor citalopram (30 mg/kg) did not. Microdialysis studies showed that atomoxetine, methylphenidate, duloxetine, venlafaxine, milnacipran, and reboxetine increased the extracellular levels of norepinephrine and dopamine in the prefrontal cortex in SHR. Citalopram did not affect norepinephrine and dopamine levels in the prefrontal cortex, although it increased the serotonin levels. Neither duloxetine nor venlafaxine increased the dopamine levels in the striatum. These findings suggest that serotonin–norepinephrine reuptake inhibitors, similar to methylphenidate and atomoxetine, have potential for ameliorating motor abnormality in the SHR model.
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lithium attenuates methamphetamine induced hyperlocomotion and behavioral sensitization via modulation of prefrontal Monoamine Release
Neuropharmacology, 2012Co-Authors: Yukio Ago, Kazuhiro Takuma, Toshio Matsuda, Tatsunori Tanaka, Yuki Kita, Hokuto TokumotoAbstract:Lithium attenuates psychostimulant-induced hyperactivity and behavioral sensitization, but the exact mechanisms are not known. Previous studies show that lithium has neuromodulatory effects on Monoamine systems. The present study was aimed to clarify whether prefrontal Monoaminergic neurotransmission is involved in the effect of lithium on methamphetamine (METH)-induced behaviors in mice. Lithium attenuated METH-induced hyperactivity and METH-induced increase in extracellular dopamine (DA), but not serotonin (5-HT), levels in the prefrontal cortex. Chronic METH caused behavioral sensitization and enhancement of METH-induced increase in prefrontal 5-HT Release (neurochemical sensitization). Co-administration of lithium with METH attenuated behavioral sensitization and neurochemical sensitization. Chronic METH also reduced the 5-HT(1A) receptor agonist osemozotan-induced decrease in prefrontal 5-HT Release (desensitization of presynaptic 5-HT(1A) autoreceptor), and this effect was reversed by co-administration of lithium. These results suggest that lithium attenuates acute METH-induced hyperactivity and chronic METH-induced behavioral sensitization via modulation of prefrontal Release of DA and 5-HT, respectively. The present study also suggests that a 5-HT(1A) receptor-mediated mechanism is involved in the effect of lithium on chronic METH-induced behavioral sensitization.