The Experts below are selected from a list of 246 Experts worldwide ranked by ideXlab platform
Tarik Dahoun - One of the best experts on this subject based on the ideXlab platform.
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The relationship between childhood trauma, dopamine release and Dexamphetamine-induced positive psychotic symptoms: a [^11C]-(+)-PHNO PET study
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [^11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D_2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants ( n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative ( p = 0.280) or general PANSS symptoms ( p = 0.061), and there was no relationship between ventral striatal baseline D_2/3R availability and positive symptoms ( p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
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the relationship between childhood trauma dopamine release and Dexamphetamine induced positive psychotic symptoms a 11c phno pet study
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
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The relationship between childhood trauma, dopamine release and Dexamphetamine-induced positive psychotic symptoms: a [11C]-(+)-PHNO PET study.
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
Jean Costentin - One of the best experts on this subject based on the ideXlab platform.
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comparisons between bupropion and Dexamphetamine in a range of in vivo tests exploring dopaminergic transmission
British Journal of Pharmacology, 2007Co-Authors: Pierre Bredeloux, I Dubuc, Jean CostentinAbstract:Background and purpose: In the present study we investigated, in a range of in vivo tests whether the antidepressant bupropion, and its metabolites shared the dopamine releasing effect of the chemically related Dexamphetamine. Experimental approach: We compared bupropion and Dexamphetamine in different neurochemical (microdialysis, DOPAC and HVA contents) and behavioural tests, assessing their effects in animals pretreated with a variety of agents (reserpine, sodium hydroxy-4-butyrate or haloperidol) known to modify dopaminergic transmission. Key results: In mice, Dexamphetamine, like bupropion, increased at low doses and reduced at high doses, locomotor activity. Dexamphetamine restored the locomotor activity in mice made akinetic by either sodium hydroxy-4-butyrate or reserpine, whereas bupropion did not. Moreover, bupropion prevented the Dexamphetamine-induced reversal of akinetic effects of reserpine. Haloperidol abolished the locomotor-stimulant effects of Dexamphetamine but did not suppress stimulation by bupropion. In microdialysis experiments, in chloral hydrate anesthetized rats, low doses of Dexamphetamine (1 mg kg−1) markedly increased the extracellular dopamine concentration in striatum (340%), while bupropion (100 mg kg−1) produced only a moderate increase (150%). Finally, in rat striatum, as well as in the nucleus accumbens, bupropion increased the effect of haloperidol on DOPAC and HVA concentrations, whereas Dexamphetamine reduced these haloperidol effects. Conclusions and implications: Considering only dopaminergic transmission, our results demonstrated that bupropion and metabolites displayed in vivo, as did bupropion in vitro, an inhibition of dopamine uptake and, contrast to Dexamphetamine, were devoid of dopamine releasing effects. British Journal of Pharmacology (2007) 150, 711–719. doi:10.1038/sj.bjp.0707151
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Behavioural and neurochemical evidence that the antimicrobial agent oxolinic acid is a dopamine uptake inhibitor
European Neuropsychopharmacology, 1998Co-Authors: J. Garcia De Mateos-verchere, J.-m. Vaugeois, B. Naudin, Jean CostentinAbstract:Abstract The antimicrobial agent oxolinic acid, injected i.p. in mice, induced a dose dependent increase in locomotor activity. This stimulation culminated at the 32 mg/kg dose and became smaller for higher doses (64–128 mg/kg). When opposed to increasing doses (50–100–200 μg/kg i.p.) of haloperidol (D2 dopamine receptor antagonist), the stimulant locomotor effect of 32 mg/kg oxolinic acid was not significantly reversed. On the contrary increasing doses (7.5–15–30 μg/kg s.c.) of SCH 23390 (D1 dopamine receptor antagonist) inhibited the stimulant locomotor effect. In mice made completely akinetic by a pretreatment with reserpine (4 mg/kg s.c., 18 h before testing), Dexamphetamine (2 mg/kg s.c.) reversed this akinesia and even displayed a stimulant activity, similar to that observed in mice not treated by reserpine. On the contrary, oxolinic acid (32 mg/kg) did not reverse the reserpine induced akinesia and even opposed the reversion induced by Dexamphetamine. In a synaptosomal fraction prepared from striatum of rats, oxolinic acid inhibited the 3 H dopamine uptake with an IC50=4.3±0.6×10−6 M. Finally, in mice injected i.v. with a tracer dose of 3 H WIN 35428 (1 μCi) (a dopamine uptake blocker), 32 mg/kg oxolinic acid, i.p. administered, reduced by about 50% the specific binding of the radioligand to striatal dopamine carriers. It is concluded that the stimulant locomotor effect of oxolinic acid depends on the blockade of the neuronal dopamine uptake complex.
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the stimulant effect of modafinil on wakefulness is not associated with an increase in anxiety in mice a comparison with Dexamphetamine
Psychopharmacology, 1994Co-Authors: Ph Simon, Ch Panissaud, Jean CostentinAbstract:Modafinil is a new drug used in the treatment of narcolepsy. Its administration in mice induced a dose-dependent increase in locomotor activity. The effects of modafinil were compared with those of Dexamphetamine on three tests that assessed the anxiety level (drugs were used at doses which induced a roughly similar stimulation of locomotor activity). Dexamphetamine increased the latency of exploration of a white compartment, increased thigmotaxis in an open-field and decreased the time spent in the open arms of an elevated plus-maze. None of these responses was significantly modified by modafinil. We conclude that modafinil does not share the anxiogenic effects of Dexamphetamine.
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relationship between the effects of Dexamphetamine on locomotion and on striatal 3h gbr 12783 binding in vivo
European Journal of Pharmacology, 1990Co-Authors: J.-m. Vaugeois, J J Bonnet, Jean CostentinAbstract:Abstract In mice, low doses (1-2-4 mg/kg s.c.) of Dexamphetamine stimulated locomotor activity in a dose-dependent manner. Over the same range of doses the drug dose dependently inhibited the in vivo striatal binding of the dopamine uptake inhibitor, [ 3 H]GBR 12783. At 3 mg/kg Dexamphetamine, the stimulant effect and the inhibition of the striatal binding of [ 3 H]GBR 12783 displayed a similar time course. Pretreatments that either increased (L-DOPA 200 mg/kg, benserazide 50 mg/kg i.p.) or decreased (reserpine 5 mg/kg s.c., α-methyl-p-tyrosine 200 mg/kg) striatal dopamine levels did not modify the inhibition by Dexamphetamine of [ 3 H]GBR 12783 binding in vivo. This suggests that the inhibition is due to a direct effect of Dexamphetamine, not mediated by endogenous dopamine, and further that a unique site is responsible for the neuronal uptake of Dexamphetamine and for the binding of pure dopamine uptake inhibitors.
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comparison of the effects of three indirect dopamine agonists gk 13 gbr 12783 and Dexamphetamine on behavioural tests involving central catecholaminergic transmissions
Psychopharmacology, 1990Co-Authors: D Duterteboucher, J M Kamenka, Jean CostentinAbstract:GK 13 (N-[1-(2-benzo (b) thiophenyl)-cyclohexyl] piperidine), GBR 12783 (1-[2-(diphenylmethoxy)ethyl] 4-(3-phenyl propenyl)-piperazine and Dexamphetamine are three indirect catecholaminergic agonists, acting via different neurochemical mechanisms. We have compared their effects in rodents, in several behavioral tests. All three drugs increased locomotion. The stimulant locomotor effect of Dexamphetamine was more easily antagonized by haloperidol than that of GBR 12783 and GK 13. Only Dexamphetamine reversed reserpine-induced akinesia. This reversal was prevented by pretreatment with either GK 13 or GBR 12783. The three drugs reduced pentobarbital sleeping time in mice. They induced rotation ipsilateral to a unilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway. The stereotypies induced by GK 13 and GBR 12783 were essentially limited to sniffing. Haloperidol-induced catalepsy was apparently more easily antagonized by Dexamphetamine than by GK 13 or GBR 12783. GK 13 and GBR 12783 had no significant effects on body temperature. The three drugs displayed an anti-immobility effect in the “despair test”. Dexamphetamine and GK 13 reversed the hypothermia induced by apomorphine (16 mg/kg), as well as reserpine-induced hypothermia and reserpine-induced ptosis. Dexamphetamine induced a dose-dependent anorectic effect, whereas GK 13 and GBR 12783 induced only a brief and partial anorexia. Similar observations were made on water intake. Pretreatment with either GBR 12783 or GK 13 did not affect the Dexamphetamine-induced anorexia. Effects of the three drugs are discussed by reference to their known neurochemical properties on catecholaminergic transmission.
Oliver D Howes - One of the best experts on this subject based on the ideXlab platform.
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The relationship between childhood trauma, dopamine release and Dexamphetamine-induced positive psychotic symptoms: a [^11C]-(+)-PHNO PET study
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [^11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D_2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants ( n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative ( p = 0.280) or general PANSS symptoms ( p = 0.061), and there was no relationship between ventral striatal baseline D_2/3R availability and positive symptoms ( p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
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the relationship between childhood trauma dopamine release and Dexamphetamine induced positive psychotic symptoms a 11c phno pet study
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
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The relationship between childhood trauma, dopamine release and Dexamphetamine-induced positive psychotic symptoms: a [11C]-(+)-PHNO PET study.
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
Robert A. Mccutcheon - One of the best experts on this subject based on the ideXlab platform.
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The relationship between childhood trauma, dopamine release and Dexamphetamine-induced positive psychotic symptoms: a [^11C]-(+)-PHNO PET study
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [^11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D_2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants ( n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative ( p = 0.280) or general PANSS symptoms ( p = 0.061), and there was no relationship between ventral striatal baseline D_2/3R availability and positive symptoms ( p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
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the relationship between childhood trauma dopamine release and Dexamphetamine induced positive psychotic symptoms a 11c phno pet study
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
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The relationship between childhood trauma, dopamine release and Dexamphetamine-induced positive psychotic symptoms: a [11C]-(+)-PHNO PET study.
Translational Psychiatry, 2019Co-Authors: Tarik Dahoun, Robert A. Mccutcheon, Michael A. P. Bloomfield, M M Nour, Rick A Adams, Oliver D HowesAbstract:Childhood trauma is a risk factor for psychosis. Amphetamine increases synaptic striatal dopamine levels and can induce positive psychotic symptoms in healthy individuals and patients with schizophrenia. Socio-developmental hypotheses of psychosis propose that childhood trauma and other environmental risk factors sensitize the dopamine system to increase the risk of psychotic symptoms, but this remains to be tested in humans. We used [11C]-(+)-PHNO positron emission tomography to measure striatal dopamine-2/3 receptor (D2/3R) availability and ventral striatal Dexamphetamine-induced dopamine release in healthy participants (n = 24). The relationships between Dexamphetamine-induced dopamine release, Dexamphetamine-induced positive psychotic symptoms using the Positive and Negative Syndrome Scale (PANSS), and childhood trauma using the Childhood Trauma Questionnaire (CTQ) were assessed using linear regression and mediation analyses, with childhood trauma as the independent variable, Dexamphetamine-induced dopamine release as the mediator variable, and Dexamphetamine-induced symptoms as the dependent variable. There was a significant interaction between childhood trauma and ventral striatal dopamine release in predicting Dexamphetamine-induced positive psychotic symptoms (standardized β = 1.83, p = 0.003), but a mediation analysis was not significant (standardized β = −0.18, p = 0.158). There were no significant effects of dopamine release and childhood trauma on change in negative (p = 0.280) or general PANSS symptoms (p = 0.061), and there was no relationship between ventral striatal baseline D2/3R availability and positive symptoms (p = 0.368). This indicates childhood trauma and dopamine release interact to influence the induction of positive psychotic symptoms. This is not consistent with a simple sensitization hypothesis, but suggests that childhood trauma moderates the cognitive response to dopamine release to make psychotic experiences more likely.
Bruce R. Russell - One of the best experts on this subject based on the ideXlab platform.
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Investigation of the effects of ‘piperazine-containing party pills’ and Dexamphetamine on interhemispheric communication using electroencephalography
Psychopharmacology, 2016Co-Authors: Grace Y Wang, R R Kydd, Louise E Curley, Ian J Kirk, Bruce R. RussellAbstract:Background ‘Piperazine-containing party pills’ were marketed and sold as legal alternatives to methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. The major constituents of these ‘pills’ were benzylphenylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP). Despite their popularity, there is a paucity of knowledge about their central effects in humans. This study investigated their effects on human neural processing using electroencephalographic techniques. Methods A randomised, double-blind, placebo-controlled study investigated the effects of an acute dose of these compounds on the interhemispheric transfer of information (IHTT) using the Poffenberger task. Reaction time data were also collected. Healthy, right-handed males were given an oral dose of either BZP ( n = 13) (200 mg), TFMPP ( n = 15) (60 mg), a combination of BZP + TFMPP ( n = 15) (100 mg/30 mg), Dexamphetamine ( n = 16) (20 mg), or placebo ( n = 23) and tested both before and 120 min after drug administration. Results A mixed factorial repeated measures analysis of variance of absolute N160 latency and contrast analysis revealed that only TFMPP ( F _(1,77) = 17.30, p ≤ 0.001) significantly reduced the absolute N160 latency. Analysis of the IHTT revealed that only TFMPP ( F _(1,77) = 5.266, p ≤ 0.02) significantly reduced the IHTT, while BZP, BZP + TFMPP and Dexamphetamine had no effect. Contrast analysis revealed that both TFMPP ( F _(1,77) = 17.30, p ≤ 0.001) and placebo ( F _(1,77) = 15.08, p ≤ 0.001) preserved the laterality of information transfer from one hemisphere to the other. Reaction time ( p > 0.05) was not significantly affected by any of the drug treatments. Conclusions The usual directional asymmetry (i.e. faster R-to-L transfer relative to L-to-R) observed in healthy control group was absent following the administration of either BZP, BZP + TFMPP or Dexamphetamine. Surprisingly, lateralised hemispheric function was not affected by TFMPP. Our findings highlight how the administration of BZP, TFMPP and BZP + TFMPP leads to changes in the pattern of information transfer.
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Acute effects of BZP, TFMPP and the combination of BZP and TFMPP in comparison to Dexamphetamine on an auditory oddball task using electroencephalography: a single-dose study
Psychopharmacology, 2016Co-Authors: Grace Y Wang, Louise E Curley, R R Kydd, Ian J Kirk, John J. Sollers, Bruce R. RussellAbstract:Rationale Piperazine-based designer drugs such as benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been marketed and sold as legal alternatives to Dexamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. When administered in combination, BZP + TFMPP have been reported to produce drug-drug synergism in rodents by stimulating the release of dopamine and serotonin. Objectives This study was to evaluate the acute event-related potential effects of BZP, TFMPP or the combination of BZP + TFMPP compared with Dexamphetamine in young healthy male adults. Methods A double-blind, randomised, placebo-controlled study investigated the effects of BZP, TFMPP, the combination of BZP + TFMPP, and Dexamphetamine on the event-related potentials during an auditory oddball task. Healthy, right-handed males were given a single oral dose of either BZP (200 mg), TFMPP (60 mg), a combination of BZP + TFMPP (100/30 mg), Dexamphetamine (20 mg) or placebo (lactose) and tested both before and 120 min after drug administration. Results A single dose of either TMFPP ( t = −2.29, p = 0.03) or Dexamphetamine ( t = −2.33, p = 0.02) significantly reduced the P300 amplitude. A similar trend was also found in BZP. In contrast, BZP and TFMPP in combination has no effect. Neither P300 latency nor the mean reaction time was affected by any of the drug treatments. In addition, neither the P100 nor the P200 component was significantly affected following any of the drug treatments. Conclusions A single oral dose of BZP or TFMPP, but not the combination of BZP/TFMPP, affected auditory sensory-evoked P300 potential in a manner similar to Dexamphetamine.
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acute effects of bzp tfmpp and the combination of bzp and tfmpp in comparison to Dexamphetamine on an auditory oddball task using electroencephalography a single dose study
Psychopharmacology, 2016Co-Authors: Grace Y Wang, Louise E Curley, R R Kydd, Ian J Kirk, John J. Sollers, Bruce R. RussellAbstract:Rationale Piperazine-based designer drugs such as benzylpiperazine (BZP) and trifluoromethylphenylpiperazine (TFMPP) have been marketed and sold as legal alternatives to Dexamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) until 2008 in New Zealand. When administered in combination, BZP + TFMPP have been reported to produce drug-drug synergism in rodents by stimulating the release of dopamine and serotonin.
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Determining the subjective and physiological effects of BZP on human females
Psychopharmacology, 2009Co-Authors: Nisha Bangs, R R Kydd, Bruce R. RussellAbstract:Background “Party pills” containing benzylpiperazine (BZP) used to be widely and legally available as recreational drugs in New Zealand. There are only two published trials on human subjects (1973), which suggested that 100 mg of BZP produced subjective and physiological effects similar to 10 mg of Dexamphetamine. The purpose of this study is to further investigate the subjective and physiological responses to BZP in females.