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Peter H Silverstone - One of the best experts on this subject based on the ideXlab platform.
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valproate attenuates Dextroamphetamine induced subjective changes more than lithium
European Neuropsychopharmacology, 2005Co-Authors: Morgan C Willson, Emily C Bell, Sanjay Dave, Sheila J Asghar, Brent M Mcgrath, Peter H SilverstoneAbstract:Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on Dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of Dextroamphetamine, and at two time points after administration. Differences in the response to Dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated Dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of Dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on Dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.
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lithium and valproate attenuate Dextroamphetamine induced changes in brain activation
Human Psychopharmacology-clinical and Experimental, 2005Co-Authors: Emily C Bell, Morgan C Willson, Sanjay Dave, Sheila J Asghar, Alan H Wilman, Peter H SilverstoneAbstract:Background Previous studies have suggested that both lithium and valproate may decrease phosphoinositol second messenger system (PI-cycle) activity. There is also evidence that Dextroamphetamine may increase PI cycle activity. It was previously demonstrated that Dextroamphetamine administration in volunteers causes a region and task dependent decrease in brain activation in healthy volunteers. The current study assessed the effect of 14 days pretreatment with lithium and valproate on these Dextroamphetamine-induced changes in regional brain activity in healthy volunteers. Methods This was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9) or placebo (n = 12). Functional images were acquired using functional magnetic resonance imaging (fMRI) while subjects performed three cognitive tasks, a word generation paradigm, a spatial attention task and a working memory task. fMRI was carried out both before and after administration of Dextroamphetamine (25 mg). Changes in the number of activated pixels and changes in the magnitude of the blood-oxygen-level-dependent (BOLD) signal after Dextroamphetamine administration were then determined. Results In keeping with previous findings Dextroamphetamine administration decreased regional brain activation in all three tasks. Pretreatment with lithium attenuated changes in the word generation paradigm and the spatial attention task, while pretreatment with valproate attenuated the changes in the working memory task. Conclusions These results suggest that both lithium and valproate can significantly attenuate Dextroamphetamine-induced changes in brain activity in a task dependent and region specific manner. This is the first human evidence to suggest that both lithium and valproate may have a similar effect on regional brain activation, conceivably via similar effects on PI-cycle activity. Copyright © 2005 John Wiley & Sons, Ltd.
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Dextroamphetamine causes a change in regional brain activity in vivo during cognitive tasks a functional magnetic resonance imaging study of blood oxygen level dependent response
Biological Psychiatry, 2004Co-Authors: Morgan C Willson, Emily C Bell, Sheila J Asghar, Alan H Wilman, Peter H SilverstoneAbstract:Background Dextroamphetamine is known to have profound effects on both subjective and physiologic measurements, but it is unclear to what extent these behavioral changes are a direct result of altered regional brain activation. One method to measure this is to use functional magnetic resonance imaging (fMRI). Methods In the present study, fMRI was used to measure both the spatial extent of changes (the number of pixels activated) and the magnitude of the blood oxygen level–dependent (BOLD) response. We examined the effects of motor, verbal, memory, and spatial attention task during fMRI in 18 healthy volunteers. Functional MRI measurements were obtained at baseline and again 75 min after an oral dose of 25 mg Dextroamphetamine. Results Dextroamphetamine caused a decrease in the number of activated pixels and the magnitude of the BOLD response during the three cognitive tasks tested but not during the motor task. These changes were region and task specific. Conclusions This is the first study to examine the effect of Dextroamphetamine on the number of activated pixels and the BOLD response during the performance of a range of cognitive and motor tasks. Our results suggest that Dextroamphetamine causes measurable decreases in brain activity in a variety of regions during cognitive tasks. These changes might be linked to behavioral changes observed after Dextroamphetamine administration and could possibly be mediated by alterations in dopaminergic activation.
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effects of Dextroamphetamine lithium chloride sodium valproate and carbamazepine on intraplatelet ca2 levels
Journal of Psychiatry & Neuroscience, 2003Co-Authors: Michele Ulrich, Sheila J Asghar, Susan Rotzinger, Paul Jurasz, Veronique A M I Tanay, Susan M J Dunn, Marek W Radomski, Andrew J Greenshaw, Peter H SilverstoneAbstract:Objective: To explore the possible involvement of second-messenger pathways in the pathophysiology of bipolar disorder and the mechanism of action of mood stabilizers, we investigated the effects of Dextroamphetamine (a model for mania) and the most widely used mood stabilizers, lithium chloride, sodium valproate and carbamazepine, on intraplatelet levels of calcium ion ([Ca 2+ ]). Design: In the first part of the study, Dextroamphetamine was administered in vivo in a double-blind, placebo-controlled, crossover design. In the second part of the study, platelets from untreated subjects were incubated in vitro with Dextroamphetamine, lithium chloride, sodium valproate or carbamazepine. Participants: Fifteen healthy men between 18 and 45 years of age. Outcome measures: Basal, thrombin-induced and serotonin- (5HT) induced intraplatelet [Ca 2+ ] determined by means of fura-2 fluorescent intensity. Results: In vivo administration of Dextroamphetamine had no effect on basal or agonist-induced intraplatelet [Ca 2+ ]. However, in vitro basal platelet [Ca 2+ ] was significantly higher in samples incubated with Dextroamphetamine (86.8 nmol/L [standard error of the mean, SEM, 3.9], p < 0.001), lithium chloride (76.4 nmol/L [SEM 3.1], p < 0.002), sodium valproate (82.7 nmol/L [SEM 3.7], p < 0.001) and carbamazepine (84.8 nmol/L [SEM 3.3], p < 0.001) than in the controls (58.2 nmol/L [SEM 2.3]). Thrombin-induced and 5-HT-induced peak cytosolic [Ca 2+ ] were significantly greater than control levels in samples incubated with carbamazepine (277.1 nmol/L [SEM 19.9] v. 195.8 nmol/L [SEM 12.2], p < 0.002; and 153.0 nmol/L [SEM 8.2] v. 115.4 nmol/L [SEM 5.7], p < 0.003, respectively). Conclusions: This study does not support the involvement of intraplatelet [Ca 2+ ] in the Dextroamphetamine model of mania; however, the modulation of intraplatelet [Ca 2+ ] by the mood stabilizers lithium chloride, sodium valproate and carbamazepine implicates intracellular [Ca 2+ ] in the therapeutic mechanisms of these drugs and the pathophysiological basis of mania.
Ken Solt - One of the best experts on this subject based on the ideXlab platform.
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RESEARCH ARTICLE Dextroamphetamine (but Not Atomoxetine) Induces Reanimation from General Anesthesia: Implications for the Roles of Dopamine and Norepinephrine in Active Emergence
2016Co-Authors: Jonathan D. Kenny, Norman E. Taylor, Emery N. Brown, Ken SoltAbstract:Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and nor-epinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of Dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, dextroamphet-amine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was adminis-tered prior to Dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg IV), the mean emergence times for rats that received normal saline (vehicle) and Dextroamphetamine (1 mg/kg IV) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although ato
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Dextroamphetamine but not atomoxetine induces reanimation from general anesthesia implications for the roles of dopamine and norepinephrine in active emergence
PLOS ONE, 2015Co-Authors: Jonathan D. Kenny, Norman E. Taylor, Emery N. Brown, Ken SoltAbstract:Methylphenidate induces reanimation (active emergence) from general anesthesia in rodents, and recent evidence suggests that dopaminergic neurotransmission is important in producing this effect. Dextroamphetamine causes the direct release of dopamine and norepinephrine, whereas atomoxetine is a selective reuptake inhibitor for norepinephrine. Like methylphenidate, both drugs are prescribed to treat Attention Deficit Hyperactivity Disorder. In this study, we tested the efficacy of Dextroamphetamine and atomoxetine for inducing reanimation from general anesthesia in rats. Emergence from general anesthesia was defined by return of righting. During continuous sevoflurane anesthesia, Dextroamphetamine dose-dependently induced behavioral arousal and restored righting, but atomoxetine did not (n = 6 each). When the D1 dopamine receptor antagonist SCH-23390 was administered prior to Dextroamphetamine under the same conditions, righting was not restored (n = 6). After a single dose of propofol (8 mg/kg IV), the mean emergence times for rats that received normal saline (vehicle) and Dextroamphetamine (1 mg/kg IV) were 641 sec and 404 sec, respectively (n = 8 each). The difference was statistically significant. Although atomoxetine reduced mean emergence time to 566 sec (n = 8), this decrease was not statistically significant. Spectral analysis of electroencephalogram recordings revealed that Dextroamphetamine and atomoxetine both induced a shift in peak power from δ (0.1–4 Hz) to θ (4–8 Hz) during continuous sevoflurane general anesthesia, which was not observed when animals were pre-treated with SCH-23390. In summary, Dextroamphetamine induces reanimation from general anesthesia in rodents, but atomoxetine does not induce an arousal response under the same experimental conditions. This supports the hypothesis that dopaminergic stimulation during general anesthesia produces a robust behavioral arousal response. In contrast, selective noradrenergic stimulation causes significant neurophysiological changes, but does not promote behavioral arousal during general anesthesia. We hypothesize that Dextroamphetamine is more likely than atomoxetine to be clinically useful for restoring consciousness in anesthetized patients, mainly due to its stimulation of dopaminergic neurotransmission.
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Dextroamphetamine administration induces significant EEG changes during continuous sevoflurane anesthesia.
2015Co-Authors: Jonathan D. Kenny, Norman E. Taylor, Emery N. Brown, Ken SoltAbstract:(A) Representative 60-second time-domain EEG recording from an individual rat during continuous sevoflurane anesthesia, with time zero indicating the administration of Dextroamphetamine (1 mg/kg IV). The EEG pattern rapidly changes to a low amplitude, high frequency rhythm after the administration of Dextroamphetamine. (B) Representative time-frequency domain spectrogram computed from 15 minutes of EEG data. Warm colors indicate high power at a given frequency, while cool colors indicate low power. A prompt shift in peak power from δ to θ is observed after the administration of Dextroamphetamine. (C) Group power spectral density from all rats (n = 3), with shaded areas indicating 95% confidence intervals. Before Dextroamphetamine administration (blue), δ power was dominant during continuous sevoflurane anesthesia. After Dextroamphetamine administration (red), statistically significant reductions in power occurred at most frequencies below 15 Hz, and peak power was shifted to θ.
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SCH-23390 inhibits the EEG changes induced by Dextroamphetamine during continuous sevoflurane anesthesia.
2015Co-Authors: Jonathan D. Kenny, Norman E. Taylor, Emery N. Brown, Ken SoltAbstract:(A) Representative 60-second time-domain EEG recording from an individual rat during continuous sevoflurane anesthesia after pre-treatment with SCH-23390 (0.5 mg/kg IV), with time zero indicating the administration of Dextroamphetamine (1 mg/kg IV). The EEG pattern remains essentially unchanged after Dextroamphetamine administration. (B) Representative time-frequency domain spectrogram computed from 15 minutes of EEG data. After the administration of SCH-23390, Dextroamphetamine does not induce a shift in peak power from δ to θ. (C) Group power spectral density from all rats (n = 3), with shaded areas indicating 95% confidence intervals. After the administration of SCH-23390 during continuous sevoflurane anesthesia (blue), Dextroamphetamine administration (red) only induced small changes in power that were statistically significant.
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Dextroamphetamine significantly decreases time to emergence from propofol anesthesia, but atomoxetine does not.
2015Co-Authors: Jonathan D. Kenny, Norman E. Taylor, Emery N. Brown, Ken SoltAbstract:(A) Rats received a bolus of propofol (8 mg/kg IV), followed by normal saline (vehicle), atomoxetine (1 mg/kg IV) or Dextroamphetamine (1 mg/kg IV). Time to emergence was defined as the time from administration of propofol to return of righting. (B) Scatter plot of time to emergence for rats that received normal saline, Dextroamphetamine, and atomoxetine after propofol. The lines represent mean values. Dextroamphetamine caused a statistically significant decrease in time to emergence compared to normal saline, whereas atomoxetine did not.
Thomas J Balkin - One of the best experts on this subject based on the ideXlab platform.
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effects of Dextroamphetamine caffeine and modafinil on psychomotor vigilance test performance after 44 h of continuous wakefulness
Journal of Sleep Research, 2008Co-Authors: William D S Killgore, Tracy L Rupp, Nancy L Grugle, Rebecca M Reichardt, Erica L Lipizzi, Thomas J BalkinAbstract:Prolonged sleep loss impairs alertness, vigilance and some higher-order cognitive and affective capacities. Some deficits can be temporarily reversed by stimulant medications including caffeine, Dextroamphetamine, and modafinil. To date, only one study has directly compared the effectiveness of these three compounds and specified the doses at which all were equally effective in restoring alertness and vigilance following 64 h of wakefulness. The present study compared the effectiveness of these same three stimulants/doses following a less extreme period of sleep loss (i.e., 44 h). Fifty-three healthy adults received a single dose of modafinil 400 mg (n = 11), Dextroamphetamine 20 mg (n = 16), caffeine 600 mg (n = 12), or placebo (n = 14) after 44 h of continuous wakefulness. After 61 h of being awake, participants obtained 12 h of recovery sleep. Psychomotor vigilance was assessed bi-hourly during waking and following recovery sleep. Relative to placebo, all three stimulants were equally effective in restoring psychomotor vigilance test speed and reducing lapses, although the duration of action was shortest for caffeine and longest for Dextroamphetamine. At these doses, caffeine was associated with the highest percentage of subjectively reported side-effects while modafinil did not differ significantly from placebo. Subsequent recovery sleep was adversely affected in the Dextroamphetamine group, but none of the stimulants had deleterious effects on postrecovery performance. Decisions regarding stimulant selection should be made with consideration of how factors such as duration of action, potential side-effects, and subsequent disruption of recovery sleep may interact with the demands of a particular operational environment.
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restoration of risk propensity during sleep deprivation caffeine Dextroamphetamine and modafinil
Aviation Space and Environmental Medicine, 2008Co-Authors: William D S Killgore, Nancy L Grugle, Desiree B Killgore, Brian P Leavitt, George I Watlington, Shanelle Mcnair, Thomas J BalkinAbstract:INTRODUCTION: Sleep deprivation alters risk-related judgments, decision-making, and behavioral control. Stimulant medications are used to restore cognitive performance, but their effects on risk-taking and judgment in sleep-deprived subjects have not been explored. METHODS: There were 54 healthy adults (29 men, 25 women; age range 18 to 36) who completed a test of cognitive ability and daily measures of risk-taking propensity, including the Brief Sensation Seeking Scale (BSSS), Evaluation of Risks (EVAR) scale, and the Balloon Analog RiskTask (BART). Following 44 h of continuous wakefulness, participants ingested caffeine 600 mg (N = 12), Dextroamphetamine 20 mg (N = 16), modafinil 400 mg (N = 12), or a placebo (N = 14) in a double blind manner, and completed risk-taking measures 2 h later (i.e., 0535). RESULTS: Relative to rested baseline, the placebo group showed a decline in risk-taking as measured by the BSSS (16% decline), EVAR Danger Seeking (32% decline) and Energy (22% decline), and BART (32% decline), consistent with previous reports of the effects of sleep deprivation. Comparisons among drug conditions showed that Dextroamphetamine restored risk-taking propensity and risky behavior to baseline levels, an effect that was significantly greater than placebo or caffeine for several indices of risk-taking, but which did not differ from modafinil. Cognitive ability was significantly correlated with changes on some risk-taking indices following stimulant administration. CONCLUSIONS: Stimulant medications, particularly Dextroamphetamine, sustained risk-related attitudes and behavior during continuous wakefulness. The extent to which stimulants restore other aspects of judgment during sleep loss remains to be determined.
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performance and alertness effects of caffeine Dextroamphetamine and modafinil during sleep deprivation
Journal of Sleep Research, 2005Co-Authors: Nancy J Wesensten, William D S Killgore, Thomas J BalkinAbstract:Stimulants may provide short-term performance and alertness enhancement during sleep loss. Caffeine 600 mg, d-amphetamine 20 mg, and modafinil 400 mg were compared during 85 h of total sleep deprivation to determine the extent to which the three agents restored performance on simple psychomotor tasks, objective alertness and tasks of executive functions. Forty-eight healthy young adults remained awake for 85 h. Performance and alertness tests were administered bi-hourly from 8:00 hours day 2 to 19:00 hours day 5. At 23:50 hours on day 4 (after 64 h awake), subjects ingested placebo, caffeine 600 mg, Dextroamphetamine 20 mg, or modafinil 400 mg (n=12 per group). Performance and alertness testing continued, and probe tasks of executive function were administered intermittently until the recovery sleep period (20:00 hours day 5 to 8:00 hours day 5). Bi-hourly postrecovery sleep testing occurred from 10:00 hours to 16:00 hours day 6. All three agents improved psychomotor vigilance speed and objectively measured alertness relative to placebo. Drugs did not affect recovery sleep, and postrecovery sleep performance for all drug groups was at presleep deprivation levels. Effects on executive function tasks were mixed, with improvement on some tasks with caffeine and modafinil, and apparent decrements with Dextroamphetamine on others. At the doses tested, caffeine, Dextroamphetamine, and modafinil are equally effective for approximately 2-4 h in restoring simple psychomotor performance and objective alertness. The duration of these benefits vary in accordance with the different elimination rates of the drugs. Whether caffeine, Dextroamphetamine, and modafinil differentially restore executive functions during sleep deprivation remains unclear. Language: en
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performance and alertness effects of caffeine Dextroamphetamine and modafinil during sleep deprivation
Journal of Sleep Research, 2005Co-Authors: Nancy J Wesensten, William D S Killgore, Thomas J BalkinAbstract:Stimulants may provide short-term performance and alertness enhancement during sleep loss. Caffeine 600 mg, d-amphetamine 20 mg, and modafinil 400 mg were compared during 85 h of total sleep deprivation to determine the extent to which the three agents restored performance on simple psychomotor tasks, objective alertness and tasks of executive functions. Forty-eight healthy young adults remained awake for 85 h. Performance and alertness tests were administered bi-hourly from 8:00 hours day 2 to 19:00 hours day 5. At 23:50 hours on day 4 (after 64 h awake), subjects ingested placebo, caffeine 600 mg, Dextroamphetamine 20 mg, or modafinil 400 mg (n=12 per group). Performance and alertness testing continued, and probe tasks of executive function were administered intermittently until the recovery sleep period (20:00 hours day 5 to 8:00 hours day 5). Bi-hourly postrecovery sleep testing occurred from 10:00 hours to 16:00 hours day 6. All three agents improved psychomotor vigilance speed and objectively measured alertness relative to placebo. Drugs did not affect recovery sleep, and postrecovery sleep performance for all drug groups was at presleep deprivation levels. Effects on executive function tasks were mixed, with improvement on some tasks with caffeine and modafinil, and apparent decrements with Dextroamphetamine on others. At the doses tested, caffeine, Dextroamphetamine, and modafinil are equally effective for approximately 2-4 h in restoring simple psychomotor performance and objective alertness. The duration of these benefits vary in accordance with the different elimination rates of the drugs. Whether caffeine, Dextroamphetamine, and modafinil differentially restore executive functions during sleep deprivation remains unclear.
Sheila J Asghar - One of the best experts on this subject based on the ideXlab platform.
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valproate attenuates Dextroamphetamine induced subjective changes more than lithium
European Neuropsychopharmacology, 2005Co-Authors: Morgan C Willson, Emily C Bell, Sanjay Dave, Sheila J Asghar, Brent M Mcgrath, Peter H SilverstoneAbstract:Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on Dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of Dextroamphetamine, and at two time points after administration. Differences in the response to Dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated Dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of Dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on Dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.
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lithium and valproate attenuate Dextroamphetamine induced changes in brain activation
Human Psychopharmacology-clinical and Experimental, 2005Co-Authors: Emily C Bell, Morgan C Willson, Sanjay Dave, Sheila J Asghar, Alan H Wilman, Peter H SilverstoneAbstract:Background Previous studies have suggested that both lithium and valproate may decrease phosphoinositol second messenger system (PI-cycle) activity. There is also evidence that Dextroamphetamine may increase PI cycle activity. It was previously demonstrated that Dextroamphetamine administration in volunteers causes a region and task dependent decrease in brain activation in healthy volunteers. The current study assessed the effect of 14 days pretreatment with lithium and valproate on these Dextroamphetamine-induced changes in regional brain activity in healthy volunteers. Methods This was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9) or placebo (n = 12). Functional images were acquired using functional magnetic resonance imaging (fMRI) while subjects performed three cognitive tasks, a word generation paradigm, a spatial attention task and a working memory task. fMRI was carried out both before and after administration of Dextroamphetamine (25 mg). Changes in the number of activated pixels and changes in the magnitude of the blood-oxygen-level-dependent (BOLD) signal after Dextroamphetamine administration were then determined. Results In keeping with previous findings Dextroamphetamine administration decreased regional brain activation in all three tasks. Pretreatment with lithium attenuated changes in the word generation paradigm and the spatial attention task, while pretreatment with valproate attenuated the changes in the working memory task. Conclusions These results suggest that both lithium and valproate can significantly attenuate Dextroamphetamine-induced changes in brain activity in a task dependent and region specific manner. This is the first human evidence to suggest that both lithium and valproate may have a similar effect on regional brain activation, conceivably via similar effects on PI-cycle activity. Copyright © 2005 John Wiley & Sons, Ltd.
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Dextroamphetamine causes a change in regional brain activity in vivo during cognitive tasks a functional magnetic resonance imaging study of blood oxygen level dependent response
Biological Psychiatry, 2004Co-Authors: Morgan C Willson, Emily C Bell, Sheila J Asghar, Alan H Wilman, Peter H SilverstoneAbstract:Background Dextroamphetamine is known to have profound effects on both subjective and physiologic measurements, but it is unclear to what extent these behavioral changes are a direct result of altered regional brain activation. One method to measure this is to use functional magnetic resonance imaging (fMRI). Methods In the present study, fMRI was used to measure both the spatial extent of changes (the number of pixels activated) and the magnitude of the blood oxygen level–dependent (BOLD) response. We examined the effects of motor, verbal, memory, and spatial attention task during fMRI in 18 healthy volunteers. Functional MRI measurements were obtained at baseline and again 75 min after an oral dose of 25 mg Dextroamphetamine. Results Dextroamphetamine caused a decrease in the number of activated pixels and the magnitude of the BOLD response during the three cognitive tasks tested but not during the motor task. These changes were region and task specific. Conclusions This is the first study to examine the effect of Dextroamphetamine on the number of activated pixels and the BOLD response during the performance of a range of cognitive and motor tasks. Our results suggest that Dextroamphetamine causes measurable decreases in brain activity in a variety of regions during cognitive tasks. These changes might be linked to behavioral changes observed after Dextroamphetamine administration and could possibly be mediated by alterations in dopaminergic activation.
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effects of Dextroamphetamine lithium chloride sodium valproate and carbamazepine on intraplatelet ca2 levels
Journal of Psychiatry & Neuroscience, 2003Co-Authors: Michele Ulrich, Sheila J Asghar, Susan Rotzinger, Paul Jurasz, Veronique A M I Tanay, Susan M J Dunn, Marek W Radomski, Andrew J Greenshaw, Peter H SilverstoneAbstract:Objective: To explore the possible involvement of second-messenger pathways in the pathophysiology of bipolar disorder and the mechanism of action of mood stabilizers, we investigated the effects of Dextroamphetamine (a model for mania) and the most widely used mood stabilizers, lithium chloride, sodium valproate and carbamazepine, on intraplatelet levels of calcium ion ([Ca 2+ ]). Design: In the first part of the study, Dextroamphetamine was administered in vivo in a double-blind, placebo-controlled, crossover design. In the second part of the study, platelets from untreated subjects were incubated in vitro with Dextroamphetamine, lithium chloride, sodium valproate or carbamazepine. Participants: Fifteen healthy men between 18 and 45 years of age. Outcome measures: Basal, thrombin-induced and serotonin- (5HT) induced intraplatelet [Ca 2+ ] determined by means of fura-2 fluorescent intensity. Results: In vivo administration of Dextroamphetamine had no effect on basal or agonist-induced intraplatelet [Ca 2+ ]. However, in vitro basal platelet [Ca 2+ ] was significantly higher in samples incubated with Dextroamphetamine (86.8 nmol/L [standard error of the mean, SEM, 3.9], p < 0.001), lithium chloride (76.4 nmol/L [SEM 3.1], p < 0.002), sodium valproate (82.7 nmol/L [SEM 3.7], p < 0.001) and carbamazepine (84.8 nmol/L [SEM 3.3], p < 0.001) than in the controls (58.2 nmol/L [SEM 2.3]). Thrombin-induced and 5-HT-induced peak cytosolic [Ca 2+ ] were significantly greater than control levels in samples incubated with carbamazepine (277.1 nmol/L [SEM 19.9] v. 195.8 nmol/L [SEM 12.2], p < 0.002; and 153.0 nmol/L [SEM 8.2] v. 115.4 nmol/L [SEM 5.7], p < 0.003, respectively). Conclusions: This study does not support the involvement of intraplatelet [Ca 2+ ] in the Dextroamphetamine model of mania; however, the modulation of intraplatelet [Ca 2+ ] by the mood stabilizers lithium chloride, sodium valproate and carbamazepine implicates intracellular [Ca 2+ ] in the therapeutic mechanisms of these drugs and the pathophysiological basis of mania.
Morgan C Willson - One of the best experts on this subject based on the ideXlab platform.
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valproate attenuates Dextroamphetamine induced subjective changes more than lithium
European Neuropsychopharmacology, 2005Co-Authors: Morgan C Willson, Emily C Bell, Sanjay Dave, Sheila J Asghar, Brent M Mcgrath, Peter H SilverstoneAbstract:Dextroamphetamine administration in healthy controls produces a range of subjective and physiological effects, which have been likened to those occurring during mania. However, it is uncertain if these can be attenuated by lithium since conflicting results have been reported. To date there have been no previous studies examining the effects of valproate on Dextroamphetamine-induced mood and physiological changes. The current study was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n=12), 900 mg lithium (n=9), or placebo (n=12) pre-treatment for 14 days. Subjective and physiological measures were then obtained prior to administration of a 25 mg dose of Dextroamphetamine, and at two time points after administration. Differences in the response to Dextroamphetamine were assessed between the three treatment groups. The results of this study show that pre-treatment with lithium only significantly attenuated Dextroamphetamine-induced change in happiness, while valproate pre-treatment significantly attenuated the effects of Dextroamphetamine on happiness, energy, alertness and on the diastolic blood pressure. These results suggest that lithium and valproate do not have the same mechanism of action on Dextroamphetamine-induced changes, and this finding may relate to differences in their mechanism of action in mood disorders.
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lithium and valproate attenuate Dextroamphetamine induced changes in brain activation
Human Psychopharmacology-clinical and Experimental, 2005Co-Authors: Emily C Bell, Morgan C Willson, Sanjay Dave, Sheila J Asghar, Alan H Wilman, Peter H SilverstoneAbstract:Background Previous studies have suggested that both lithium and valproate may decrease phosphoinositol second messenger system (PI-cycle) activity. There is also evidence that Dextroamphetamine may increase PI cycle activity. It was previously demonstrated that Dextroamphetamine administration in volunteers causes a region and task dependent decrease in brain activation in healthy volunteers. The current study assessed the effect of 14 days pretreatment with lithium and valproate on these Dextroamphetamine-induced changes in regional brain activity in healthy volunteers. Methods This was a double-blind, placebo-controlled, study in which volunteers received either 1000 mg sodium valproate (n = 12), 900 mg lithium (n = 9) or placebo (n = 12). Functional images were acquired using functional magnetic resonance imaging (fMRI) while subjects performed three cognitive tasks, a word generation paradigm, a spatial attention task and a working memory task. fMRI was carried out both before and after administration of Dextroamphetamine (25 mg). Changes in the number of activated pixels and changes in the magnitude of the blood-oxygen-level-dependent (BOLD) signal after Dextroamphetamine administration were then determined. Results In keeping with previous findings Dextroamphetamine administration decreased regional brain activation in all three tasks. Pretreatment with lithium attenuated changes in the word generation paradigm and the spatial attention task, while pretreatment with valproate attenuated the changes in the working memory task. Conclusions These results suggest that both lithium and valproate can significantly attenuate Dextroamphetamine-induced changes in brain activity in a task dependent and region specific manner. This is the first human evidence to suggest that both lithium and valproate may have a similar effect on regional brain activation, conceivably via similar effects on PI-cycle activity. Copyright © 2005 John Wiley & Sons, Ltd.
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Dextroamphetamine causes a change in regional brain activity in vivo during cognitive tasks a functional magnetic resonance imaging study of blood oxygen level dependent response
Biological Psychiatry, 2004Co-Authors: Morgan C Willson, Emily C Bell, Sheila J Asghar, Alan H Wilman, Peter H SilverstoneAbstract:Background Dextroamphetamine is known to have profound effects on both subjective and physiologic measurements, but it is unclear to what extent these behavioral changes are a direct result of altered regional brain activation. One method to measure this is to use functional magnetic resonance imaging (fMRI). Methods In the present study, fMRI was used to measure both the spatial extent of changes (the number of pixels activated) and the magnitude of the blood oxygen level–dependent (BOLD) response. We examined the effects of motor, verbal, memory, and spatial attention task during fMRI in 18 healthy volunteers. Functional MRI measurements were obtained at baseline and again 75 min after an oral dose of 25 mg Dextroamphetamine. Results Dextroamphetamine caused a decrease in the number of activated pixels and the magnitude of the BOLD response during the three cognitive tasks tested but not during the motor task. These changes were region and task specific. Conclusions This is the first study to examine the effect of Dextroamphetamine on the number of activated pixels and the BOLD response during the performance of a range of cognitive and motor tasks. Our results suggest that Dextroamphetamine causes measurable decreases in brain activity in a variety of regions during cognitive tasks. These changes might be linked to behavioral changes observed after Dextroamphetamine administration and could possibly be mediated by alterations in dopaminergic activation.