Shitij Kapur

Summary

Affiliation: Centre for Addiction and Mental Health
Country: Canada

Publications

  1. ncbi request reprint From dopamine to salience to psychosis--linking biology, pharmacology and phenomenology of psychosis
    Shitij Kapur
    Centre for Addiction and Mental Health, Toronto, Canada
    Schizophr Res 79:59-68. 2005
  2. ncbi request reprint Evidence for onset of antipsychotic effects within the first 24 hours of treatment
    Shitij Kapur
    Centre for Addiction and Mental Health, 250 College St, Toronto, Ont, Canada M5R 1T8
    Am J Psychiatry 162:939-46. 2005
  3. pmc How antipsychotics work-from receptors to reality
    Shitij Kapur
    Centre for Addiction and Mental Health, Toronto, Canada M5S 1A1 University of Toronto, Toronto, Canada
    NeuroRx 3:10-21. 2006
  4. ncbi request reprint Direct activation of the ventral striatum in anticipation of aversive stimuli
    Jimmy Jensen
    PET Centre, Centre for Addiction and Mental Health, Baycrest Geriatric Centre, Toronto, Ontario, Canada
    Neuron 40:1251-7. 2003
  5. ncbi request reprint Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans
    Ariel Graff-Guerrero
    PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Hum Brain Mapp 29:400-10. 2008
  6. ncbi request reprint Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study
    David Mamo
    Department of Psychiatry, University of Toronto, Toronto, Canada
    Am J Psychiatry 164:1411-7. 2007
  7. doi request reprint Amisulpride the 'atypical' atypical antipsychotic--comparison to haloperidol, risperidone and clozapine
    Sridhar Natesan
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health CAMH, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    Schizophr Res 105:224-35. 2008
  8. ncbi request reprint Evaluation of N-desmethylclozapine as a potential antipsychotic--preclinical studies
    Sridhar Natesan
    1Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:1540-9. 2007
  9. ncbi request reprint Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography
    Nathalie Ginovart
    The Vivian Rakoff Positron Emission Tomography Unit, Center for Addiction and Mental Health, Toronto, Canada
    J Neurochem 97:1089-103. 2006
  10. ncbi request reprint In vivo characterization of the pharmacokinetics and pharmacological properties of [11C]-(+)-PHNO in rats using an intracerebral beta-sensitive system
    Laurent Galineau
    The Vivian Rakoff Positron Emission Tomography Unit, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Synapse 60:172-83. 2006

Collaborators

Detail Information

Publications92

  1. ncbi request reprint From dopamine to salience to psychosis--linking biology, pharmacology and phenomenology of psychosis
    Shitij Kapur
    Centre for Addiction and Mental Health, Toronto, Canada
    Schizophr Res 79:59-68. 2005
    ..The article discusses the caveats, limitations as well as the clinical implications of the salience framework...
  2. ncbi request reprint Evidence for onset of antipsychotic effects within the first 24 hours of treatment
    Shitij Kapur
    Centre for Addiction and Mental Health, 250 College St, Toronto, Ont, Canada M5R 1T8
    Am J Psychiatry 162:939-46. 2005
    ..Recent research has shown that antipsychotic action begins within the first week. The authors tested the hypothesis that psychosis improves within the first 24 hours of antipsychotic treatment...
  3. pmc How antipsychotics work-from receptors to reality
    Shitij Kapur
    Centre for Addiction and Mental Health, Toronto, Canada M5S 1A1 University of Toronto, Toronto, Canada
    NeuroRx 3:10-21. 2006
    ..The implications of these findings for clinical care, animal models, future target discovery and drug development are discussed...
  4. ncbi request reprint Direct activation of the ventral striatum in anticipation of aversive stimuli
    Jimmy Jensen
    PET Centre, Centre for Addiction and Mental Health, Baycrest Geriatric Centre, Toronto, Ontario, Canada
    Neuron 40:1251-7. 2003
    ..Our data suggest that the ventral striatum, a crucial element of the brain "reward" system, is directly activated in anticipation of aversive stimuli...
  5. ncbi request reprint Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans
    Ariel Graff-Guerrero
    PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Hum Brain Mapp 29:400-10. 2008
    ..This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease...
  6. ncbi request reprint Differential effects of aripiprazole on D(2), 5-HT(2), and 5-HT(1A) receptor occupancy in patients with schizophrenia: a triple tracer PET study
    David Mamo
    Department of Psychiatry, University of Toronto, Toronto, Canada
    Am J Psychiatry 164:1411-7. 2007
    ..The authors conducted a positron emission tomography (PET) study to characterize the simultaneous effects of aripiprazole at the D(2), 5-HT(2), and 5-HT(1A) receptors in patients with schizophrenia or schizoaffective disorder...
  7. doi request reprint Amisulpride the 'atypical' atypical antipsychotic--comparison to haloperidol, risperidone and clozapine
    Sridhar Natesan
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health CAMH, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    Schizophr Res 105:224-35. 2008
    ....
  8. ncbi request reprint Evaluation of N-desmethylclozapine as a potential antipsychotic--preclinical studies
    Sridhar Natesan
    1Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:1540-9. 2007
    ....
  9. ncbi request reprint Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography
    Nathalie Ginovart
    The Vivian Rakoff Positron Emission Tomography Unit, Center for Addiction and Mental Health, Toronto, Canada
    J Neurochem 97:1089-103. 2006
    ....
  10. ncbi request reprint In vivo characterization of the pharmacokinetics and pharmacological properties of [11C]-(+)-PHNO in rats using an intracerebral beta-sensitive system
    Laurent Galineau
    The Vivian Rakoff Positron Emission Tomography Unit, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Synapse 60:172-83. 2006
    ..These results substantiate the use of [11C]-(+)-PHNO as an agonist radiotracer for D2-imaging. The sensitivity of its binding to competition with endogenous DA suggests an association with the subset of high affinity state D2-receptors...
  11. ncbi request reprint Striatal vs extrastriatal dopamine D2 receptors in antipsychotic response--a double-blind PET study in schizophrenia
    Ofer Agid
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:1209-15. 2007
    ....
  12. ncbi request reprint First human evidence of d-amphetamine induced displacement of a D2/3 agonist radioligand: A [11C]-(+)-PHNO positron emission tomography study
    Matthaus Willeit
    Positron Emission Tomography Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada
    Neuropsychopharmacology 33:279-89. 2008
    ..11)C]-(+)-PHNO PET might be a superior measure for release of endogenous dopamine than PET employing conventional D(2/3) antagonist radioligands...
  13. doi request reprint Sensitivity of older patients to antipsychotic motor side effects: a PET study examining potential mechanisms
    Hiroyuki Uchida
    Schizophrenia Research Group, PET Centre, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada
    Am J Geriatr Psychiatry 17:255-63. 2009
    ..The objective of this study was to examine whether this sensitivity is due to a central pharmacokinetic (i.e., higher occupancy for a given plasma level) or pharmacodynamic (i.e., greater functional effects for a given occupancy) effect...
  14. ncbi request reprint Positron emission tomography quantification of [11C]-(+)-PHNO binding in the human brain
    Nathalie Ginovart
    The Vivian Rakoff Positron Emission Tomography Unit, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    J Cereb Blood Flow Metab 27:857-71. 2007
    ..This study demonstrates that [11C]-(+)-PHNO can be used for the quantitative measurement of D2/3 densities and should enable further studies of potential D2/3 dysregulation in several important psychiatric and neurologic illnesses...
  15. doi request reprint Less is more: antipsychotic drug effects are greater with transient rather than continuous delivery
    Anne Noël Samaha
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Biol Psychiatry 64:145-52. 2008
    ..Based on prior data, we predicted that variations in the within-day kinetics of antipsychotic drug delivery would produce different outcomes, even if we held achieved dose, route, and total duration of treatment constant...
  16. doi request reprint Dopamine-induced changes in neural network patterns supporting aversive conditioning
    Andreea Oliviana Diaconescu
    Rotman Research Institute, Baycrest Centre for Geriatric Care, Toronto, Ontario, Canada
    Brain Res 1313:143-61. 2010
    ..These data provide insight into the distinct effects of DA agents on the functional connectivity between striatal, limbic, and prefrontal areas...
  17. ncbi request reprint Adverse subjective experience with antipsychotics and its relationship to striatal and extrastriatal D2 receptors: a PET study in schizophrenia
    Romina Mizrahi
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5S 2S1
    Am J Psychiatry 164:630-7. 2007
    ..The authors present the first double-blind controlled study to examine the relationship between striatal and extrastriatal dopamine D(2) receptor binding potential and occupancy values and adverse subjective experience...
  18. ncbi request reprint Monthly administration of long-acting injectable risperidone and striatal dopamine D2 receptor occupancy for the management of schizophrenia
    Hiroyuki Uchida
    Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    J Clin Psychiatry 69:1281-6. 2008
    ..The objective of this positron emission tomography (PET) study was to examine the striatal dopamine D(2) binding of long-acting risperidone administered intramuscularly once a month...
  19. doi request reprint The dopamine D2 receptors in high-affinity state and D3 receptors in schizophrenia: a clinical [11C]-(+)-PHNO PET study
    Ariel Graff-Guerrero
    PET Centre, Centre for Addiction and Mental Health, Toronto, Canada
    Neuropsychopharmacology 34:1078-86. 2009
    ..It is possible that receptors with high affinity are not accessible by [(11)C]-(+)-PHNO because they are occupied by endogenous dopamine, a possibility that can be ruled out in future experiments...
  20. ncbi request reprint The dopamine stabilizers (S)-(-)-(3-methanesulfonyl-phenyl)-1-propyl-piperidine [(-)-OSU6162] and 4-(3-methanesulfonylphenyl)-1-propyl-piperidine (ACR16) show high in vivo D2 receptor occupancy, antipsychotic-like efficacy, and low potential for motor sid
    Sridhar Natesan
    Schizophrenia Program and PET Centre, Toronto, Ontario, Canada
    J Pharmacol Exp Ther 318:810-8. 2006
    ..The results suggest that dopamine stabilizers exhibit locomotor stabilizing as well as antipsychotic-like effects, with low motor side effect liability, in a dose range that corresponds to high D2 in vivo occupancy...
  21. ncbi request reprint The formation of abnormal associations in schizophrenia: neural and behavioral evidence
    Jimmy Jensen
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 33:473-9. 2008
    ..The aberrant activations and response are consistent with the idea that patients aberrantly assign motivational salience to neutral stimuli, and this process may be one of the aberrations that predisposes them to psychosis...
  22. doi request reprint Decreased binding of the D3 dopamine receptor-preferring ligand [11C]-(+)-PHNO in drug-naive Parkinson's disease
    Isabelle Boileau
    Human Neurochemical Pathology Laboratory, University of Toronto, Toronto, Ontario, Canada
    Brain 132:1366-75. 2009
    ....
  23. ncbi request reprint Dissociation between in vivo occupancy and functional antagonism of dopamine D2 receptors: comparing aripiprazole to other antipsychotics in animal models
    Sridhar Natesan
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 31:1854-63. 2006
    ..Partial agonism of aripiprazole offers a good explanation for this dissociation and provides a framework for understanding occupancy-functional relationships of partial D2 agonist antipsychotics...
  24. ncbi request reprint Early use of clozapine for poorly responding first-episode psychosis
    Ofer Agid
    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    J Clin Psychopharmacol 27:369-73. 2007
    ..The present findings suggest that clozapine may have an important role in the early treatment of first-episode patients whose psychosis does not remit with other second-generation antipsychotics during the first months of treatment...
  25. ncbi request reprint Continuous but not intermittent olanzapine infusion induces vacuous chewing movements in rats
    Peter Turrone
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    Biol Psychiatry 57:406-11. 2005
    ..The objective of this study was to determine whether continuous, versus intermittent, olanzapine (OLZ) infusion differently affects the development of VCMs...
  26. doi request reprint Tetrabenazine augmentation in treatment-resistant schizophrenia: a 12-week, double-blind, placebo-controlled trial
    Gary Remington
    Department of Psychiatry, University of Toronto, Toronto, Canada
    J Clin Psychopharmacol 32:95-9. 2012
    ....
  27. doi request reprint Exploring the neural correlates of delusions of reference
    Mahesh Menon
    Department of Psychiatry, University of Toronto, Toronto, Canada
    Biol Psychiatry 70:1127-33. 2011
    ..The cortical midline structures (CMS) and subcortical regions, including the amygdala and striatum, are linked with self-reference in healthy adults. Less is known about the neural substrates of altered self-reference in schizophrenia...
  28. ncbi request reprint A PET study evaluating dopamine D2 receptor occupancy for long-acting injectable risperidone
    Gary Remington
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ont M5T 1R8, Canada
    Am J Psychiatry 163:396-401. 2006
    ..The present study used positron emission tomography (PET) to evaluate its dopamine D(2) binding profile at doses of 25, 50, or 75 mg administered every 2 weeks...
  29. doi request reprint D2-receptor upregulation is dependent upon temporal course of D2-occupancy: a longitudinal [11C]-raclopride PET study in cats
    Nathalie Ginovart
    The Vivian Rakoff Positron Emission Tomography Unit, Centre for Addiction and Mental Health and University of Toronto, Toronto, ON, Canada
    Neuropsychopharmacology 34:662-71. 2009
    ..This suggests that as far as antipsychotics are concerned, not only dose but disbursment throughout the day have an impact on eventual pharmacodynamic and behavioral outcomes...
  30. doi request reprint "Extended" antipsychotic dosing in the maintenance treatment of schizophrenia: a double-blind, placebo-controlled trial
    Gary Remington
    Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario M5T 1R8, Canada
    J Clin Psychiatry 72:1042-8. 2011
    ..Based on a better understanding of the brain kinetics of antipsychotics, we have proposed a variation of this approach, "extended" dosing, which allows for intermittent but regular dosing...
  31. doi request reprint The relationship between subjective well-being and dopamine D2 receptors in patients treated with a dopamine partial agonist and full antagonist antipsychotics
    Romina Mizrahi
    Centre for Addiction and Mental Health, PET Centre, Toronto, ON, Canada
    Int J Neuropsychopharmacol 12:715-21. 2009
    ..90 (S.D.=15.33), an effect that was sustained for 6 months. This sustained improvement was observed despite very high levels of DA D2 occupancy (82-99%), in contrast to the effects of antagonist antipsychotics on subjective well-being...
  32. doi request reprint D2 receptor blockade by risperidone correlates with attention deficits in late-life schizophrenia
    Hiroyuki Uchida
    PET Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    J Clin Psychopharmacol 29:571-5. 2009
    ....
  33. doi request reprint Blockade of [11C](+)-PHNO binding in human subjects by the dopamine D3 receptor antagonist ABT-925
    Ariel Graff-Guerrero
    PET Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Int J Neuropsychopharmacol 13:273-87. 2010
    ..Thus, [11C](+)-PHNO seems a suitable PET radiotracer to estimate D3 receptor occupancy in humans...
  34. ncbi request reprint A sensitizing regimen of amphetamine impairs visual attention in the 5-choice serial reaction time test: reversal by a D1 receptor agonist injected into the medial prefrontal cortex
    Paul J Fletcher
    Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:1122-32. 2007
    ..The reversal of these deficits by a D1 receptor agonist provides further evidence that prefrontal D1 dopamine receptors are involved in cognition, and may be a potential target for treatment of impaired cognition in schizophrenia...
  35. ncbi request reprint Quetiapine: an effective antipsychotic in first-episode schizophrenia despite only transiently high dopamine-2 receptor blockade
    Sitra Tauscher-Wisniewski
    Schizophrenia and Continuing Care Program, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Canada
    J Clin Psychiatry 63:992-7. 2002
    ..We treated patients experiencing their first episode of schizophrenia with a single daily dose of quetiapine to achieve a transient daily peak of D(2) receptor blockade, to determine if this would lead to an antipsychotic response...
  36. pmc The antipsychotics olanzapine, risperidone, clozapine, and haloperidol are D2-selective ex vivo but not in vitro
    Patrick N McCormick
    Institute of Medical Science, University of Toronto, Toronto, ON, Canada
    Neuropsychopharmacology 35:1826-35. 2010
    ..This unforeseen finding suggests that their clinical effects cannot be attributed to D3 receptor blockade...
  37. doi request reprint Effects of antipsychotics on D3 receptors: a clinical PET study in first episode antipsychotic naive patients with schizophrenia using [11C]-(+)-PHNO
    Romina Mizrahi
    PET Centre, Centre for Addiction and Mental Health, Toronto, Canada
    Schizophr Res 131:63-8. 2011
    ..11)C]-(+)-PHNO offer new opportunities for exploring the potential therapeutic significance of the D(3) receptor in schizophrenia and the action of antipsychotics...
  38. ncbi request reprint 'Jumping to conclusions' and delusions in psychosis: relationship and response to treatment
    Mahesh Menon
    Schizophrenia Program and PET Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Canada
    Schizophr Res 98:225-31. 2008
    ..The findings suggest that JTC might moderate the effects of treatment on symptomatology, but it does not mediate the treatment induced reduction in delusional intensity...
  39. ncbi request reprint Quetiapine extended-release versus immediate-release formulation: a positron emission tomography study
    David C Mamo
    Centre for Addiction and Mental Health, PET Centre, Toronto, Ontario, Canada
    J Clin Psychiatry 69:81-6. 2008
    ..An extended-release (XR) formulation of quetiapine is currently being developed to achieve similar efficacy using a once-daily dosing regimen. We compared the central D(2) receptor binding between the IR and XR formulations...
  40. doi request reprint An algorithm-based approach to first-episode schizophrenia: response rates over 3 prospective antipsychotic trials with a retrospective data analysis
    Ofer Agid
    Schizophrenia Program, Centre for Addiction and Mental Health, 250 College St, Toronto, Ontario, M5T 1R8, Canada
    J Clin Psychiatry 72:1439-44. 2011
    ..Employing a naturalistic design, we examined response rates over 3 circumscribed antipsychotic trials...
  41. ncbi request reprint Time course of the antipsychotic effect and the underlying behavioral mechanisms
    Ming Li
    Schizophrenia PET program, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:263-72. 2007
    ....
  42. ncbi request reprint A positron emission tomography study of 5-hydroxytryptamine-1A receptors in Alzheimer disease
    Krista L Lanctot
    Neuropharmacology Research Program and Geriatric Psychiatry, Toronto, Ontario, Canada
    Am J Geriatr Psychiatry 15:888-98. 2007
    ..Postmortem studies suggest decreased 5-HT(1A) receptors in patients with Alzheimer disease (AD), but this has not been confirmed in vivo. Our primary objective was to assess the extent of 5-HT(1A) receptor losses in mild to moderate AD...
  43. ncbi request reprint High-affinity states of human brain dopamine D2/3 receptors imaged by the agonist [11C]-(+)-PHNO
    Matthaus Willeit
    Positron Emission Tomography Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada
    Biol Psychiatry 59:389-94. 2006
    ....
  44. doi request reprint Gestational treatment with methylazoxymethanol (MAM) that disrupts hippocampal-dependent memory does not alter behavioural response to cocaine
    Robert E Featherstone
    Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Pharmacol Biochem Behav 93:382-90. 2009
    ..MAM treatment disrupted performance of the win-shift task but did not alter cocaine self-administration or cocaine-induced locomotion. Implications of these results for the MAM model of schizophrenia are discussed...
  45. doi request reprint Is desire for social relationships mediated by the serotonergic system in the prefrontal cortex? An [(18)F]setoperone PET study
    Philip Gerretsen
    University of Toronto, Toronto, Canada
    Soc Neurosci 5:375-83. 2010
    ..501, p = .017). These correlations were corroborated by a voxel-wise analysis. These results suggest that the serotonergic system may have a regulatory effect on the OFC and ACC for establishing and maintaining social relationships...
  46. ncbi request reprint Dopamine D2 receptor radiotracers [(11)C](+)-PHNO and [(3)H]raclopride are indistinguishably inhibited by D2 agonists and antagonists ex vivo
    Patrick N McCormick
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Nucl Med Biol 35:11-7. 2008
    ....
  47. doi request reprint A sensitizing regimen of amphetamine that disrupts attentional set-shifting does not disrupt working or long-term memory
    Robert E Featherstone
    Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada M5T 1R8
    Behav Brain Res 189:170-9. 2008
    ....
  48. pmc Dopaminergic activity in depressed smokers: a positron emission tomography study
    Usoa E Busto
    Clinical Neuroscience Section, Neuroscience Research Department, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Synapse 63:681-9. 2009
    ..Comorbid major depression and tobacco dependence exacerbates this effect, suggesting an altered dopamine system in comorbid patients...
  49. doi request reprint Ex vivo [11C]-(+)-PHNO binding is unchanged in animal models displaying increased high-affinity states of the D2 receptor in vitro
    Patrick N McCormick
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada M5S1A8
    Synapse 63:998-1009. 2009
    ..The potential implications of this discrepancy are discussed...
  50. pmc Schizophrenia, amphetamine-induced sensitized state and acute amphetamine exposure all show a common alteration: increased dopamine D2 receptor dimerization
    Min Wang
    Department of Neuroscience, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Mol Brain 3:25. 2010
    ....
  51. ncbi request reprint Effect of antipsychotics on cortical inhibition using transcranial magnetic stimulation
    Zafiris J Daskalakis
    Schizophrenia Program, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    Psychopharmacology (Berl) 170:255-62. 2003
    ..Therefore, single administration of an antipsychotic has no effect on CI or resting motor threshold. Whether chronic, repeated administration of antipsychotics has effects on CI requires further investigation...
  52. ncbi request reprint Temporal difference modeling of the blood-oxygen level dependent response during aversive conditioning in humans: effects of dopaminergic modulation
    Mahesh Menon
    Schizophrenia Program and PET Centre, Centre for Addiction and Mental Health, Toronto, Canada
    Biol Psychiatry 62:765-72. 2007
    ....
  53. ncbi request reprint The selective effect of antipsychotics on the different dimensions of the experience of psychosis in schizophrenia spectrum disorders
    Romina Mizrahi
    CAMH, and Department of Psychiatry, Faculty of Medicine, University of Toronto, Ontario, Canada
    Schizophr Res 88:111-8. 2006
    ....
  54. ncbi request reprint Amphetamine pretreatment induces a change in both D2-Receptor density and apparent affinity: a [11C]raclopride positron emission tomography study in cats
    Nathalie Ginovart
    Positron Emission Tomography Centre, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    Biol Psychiatry 55:1188-94. 2004
    ..To test this, we used PET and a Scatchard approach to investigate whether the decrease in [11C]raclopride binding following amphetamine results from competitive or noncompetitive interactions with DA...
  55. ncbi request reprint Radiosynthesis and evaluation of [11C]-(+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol as a potential radiotracer for in vivo imaging of the dopamine D2 high-affinity state with positron emission tomography
    Alan A Wilson
    PET Centre, Centre for Addiction and Mental Health and Department of Psychiatry, University of Toronto, Ontario, Canada
    J Med Chem 48:4153-60. 2005
    ....
  56. ncbi request reprint Effects of chronic typical and atypical antipsychotic drug treatment on maternal behavior in rats
    Ming Li
    Center for Addiction and Mental Health, Clarke Site, Toronto, Ontario, Canada M5R 1T8
    Schizophr Res 75:325-36. 2005
    ..It is concluded that chronic antipsychotic treatment disrupts active maternal behaviors and this disruption, most likely to lead to side effects in humans, should be avoided in future drug development...
  57. ncbi request reprint Gestational methylazoxymethanol acetate treatment impairs select cognitive functions: parallels to schizophrenia
    Robert E Featherstone
    Section of Biopsychology, Centre for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 32:483-92. 2007
    ..These results support the notion that MAM treatment may simulate some aspects of schizophrenic cognition...
  58. ncbi request reprint Separate brain regions code for salience vs. valence during reward prediction in humans
    Jimmy Jensen
    Schizophrenia Program and the PET Centre, Centre for Addiction and Mental Health, Toronto, Canada
    Hum Brain Mapp 28:294-302. 2007
    ..Given its location at the interface of limbic and motor regions, the ventral striatum may be critical in learning about motivationally salient stimuli, regardless of valence, and using that information to bias selection of actions...
  59. ncbi request reprint Sensitization to amphetamine, but not PCP, impairs attentional set shifting: reversal by a D1 receptor agonist injected into the medial prefrontal cortex
    Paul J Fletcher
    Section of Biopsychology, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, M5T 1R8, Canada
    Psychopharmacology (Berl) 183:190-200. 2005
    ..These disorders are characterized by cognitive deficits, particularly in prefrontally mediated executive function...
  60. pmc Antipsychotic dosing: how much but also how often?
    Gary Remington
    Faculty of Medicine, Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
    Schizophr Bull 36:900-3. 2010
    ..Does this mean we need to (or should) administer antipsychotics at least daily? There is a body of evidence challenging this long-established clinical axiom...
  61. pmc Actigraphic measurement of the effects of single-dose haloperidol and olanzapine on spontaneous motor activity in normal subjects
    Michael Kiang
    Schizophrenia Division, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, Toronto, Ont
    J Psychiatry Neurosci 28:293-9. 2003
    ..To quantitatively examine the effects of haloperidol and olanzapine on spontaneous motor activity in normal subjects...
  62. ncbi request reprint Dopamine D2 and D3 receptors in human putamen, caudate nucleus, and globus pallidus
    Philip Seeman
    Department of Pharmacology, University of Toronto, King s College Circle, Medical Sciences Building, Toronto, Ontario, Canada M5S 1A8
    Synapse 60:205-11. 2006
    ..The present findings are in good agreement with the known gene expression data for D2 and D3 receptors in these human brain regions...
  63. ncbi request reprint Amphetamine-sensitized animals show a sensorimotor gating and neurochemical abnormality similar to that of schizophrenia
    Catherine C Tenn
    Schizophrenia PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
    Schizophr Res 64:103-14. 2003
    ....
  64. ncbi request reprint "Breakthrough" dopamine supersensitivity during ongoing antipsychotic treatment leads to treatment failure over time
    Anne Noël Samaha
    Schizophrenia Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada M5T 1R8
    J Neurosci 27:2979-86. 2007
    ..These findings provide a model and a mechanism for antipsychotic treatment failure and suggest new directions for the development of more effective antipsychotics...
  65. ncbi request reprint The relationship between dopamine D2 receptor occupancy and the vacuous chewing movement syndrome in rats
    Peter Turrone
    Centre for Addiction and Mental Health, Schizophrenia and Continuing Care Program, 250 College Street, Room 745, Toronto, Ontario, Canada M5T 1R8
    Psychopharmacology (Berl) 165:166-71. 2003
    ..A dose-response relationship between dopamine D(2) occupancy and acute extrapyramidal symptoms (EPS) has been well established. However, the link with the induction of tardive dyskinesia (TD) is less clear...
  66. doi request reprint Attribution style as a factor in psychosis and symptom resolution
    Romina Mizrahi
    CAMH, PET Centre, Toronto, Ontario, Canada
    Schizophr Res 104:220-7. 2008
    ....
  67. ncbi request reprint Increased dopamine D2(High) receptors in amphetamine-sensitized rats, measured by the agonist [(3)H](+)PHNO
    Philip Seeman
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
    Synapse 61:263-7. 2007
    ..2-3.5-fold increase of DA D2(High) receptors may explain why amphetamine-sensitized animals are much more sensitive to DA agonists, even though the total density of D2 receptors may apparently be unchanged or even decreased...
  68. ncbi request reprint Amphetamine-sensitized animals show a marked increase in dopamine D2 high receptors occupied by endogenous dopamine, even in the absence of acute challenges
    Philip Seeman
    Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada M5S 1A8
    Synapse 46:235-9. 2002
    ....
  69. ncbi request reprint How antipsychotics become anti-"psychotic"--from dopamine to salience to psychosis
    Shitij Kapur
    Centre for Addiction and Mental Health, and the University of Toronto, 33 Russell Street Toronto, Ontario M5S 2S1, Canada
    Trends Pharmacol Sci 25:402-6. 2004
    ..The implications of this framework for relapse and other clinical phenomena, animal models and future studies are discussed...
  70. ncbi request reprint Elevation of prolactin levels by atypical antipsychotics
    Peter Turrone
    Department of Psychiatry, University of Toronto, Ont, Canada
    Am J Psychiatry 159:133-5. 2002
    ..Atypical antipsychotics are thought not to elevate prolactin levels. The authors examined data suggesting that atypical antipsychotics do elevate prolactin levels but more transiently than typical antipsychotics...
  71. doi request reprint Early onset of antipsychotic response in the treatment of acutely agitated patients with psychotic disorders
    Ofer Agid
    Center for Addiction and Mental Health, 250 College St, Toronto, Ontario, Canada M5T 1R8
    Schizophr Res 102:241-8. 2008
    ..The objective of this study was to evaluate the early response (within the first 24 h) in psychosis with ziprasidone IM treatment, and to determine whether this early effect is distinct from a reduction in agitation symptoms...
  72. ncbi request reprint Stimulation of the subthalamic nucleus in Parkinson's disease does not produce striatal dopamine release
    Aviva Abosch
    Department of Surgery, Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, and University Health Network, University of Toronto, Toronto, Ontario, Canada
    Neurosurgery 53:1095-102; discussion 1102-5. 2003
    ..We sought to determine whether STN stimulation could release endogenous striatal dopamine...
  73. ncbi request reprint Effects of typical and atypical antipsychotic drugs on maternal behavior in postpartum female rats
    Ming Li
    Centre for Addiction and Mental Health, The Clarke Division of CAMH, PET Centre, Clarke Site, 250 College Street, Toronto, Ontario M5T 1T8, Canada
    Schizophr Res 70:69-80. 2004
    ..This effect may be intrinsic to antipsychotic activity or may be reflective of a side-effect. Since the latter is more likely, this may be an effect to avoid in the design of future antipsychotics...
  74. ncbi request reprint Effects of catecholamine depletion on D2 receptor binding, mood, and attentiveness in humans: a replication study
    Nicolaas P L G Verhoeff
    Kunin Lunenfeld Applied Research Unit, Baycrest Centre for Geriatric Care, Posluns Building, 7th Floor, Room 762, 3560 Bathurst Street, Toronto, Ontario, Canada M6A 2E1
    Pharmacol Biochem Behav 74:425-32. 2003
    ..These changes were not correlated with the D(2)RBP increments. The results of this study are overall consistent with previous findings by our group using the same methodology in a different cohort of six healthy subjects...
  75. ncbi request reprint Evidence for impaired cortical inhibition in schizophrenia using transcranial magnetic stimulation
    Zafiris J Daskalakis
    Schizophrenia and Continuing Care Program, Centre for Addiction and Mental Health, Department of Psychiatry, Toronto Western General Hospital, University of Toronto, Ontario, Canada
    Arch Gen Psychiatry 59:347-54. 2002
    ....
  76. ncbi request reprint D2 receptor occupancy of olanzapine pamoate depot using positron emission tomography: an open-label study in patients with schizophrenia
    David Mamo
    Center for Addiction and Mental Health, Toronto, ON, Canada
    Neuropsychopharmacology 33:298-304. 2008
    ..However, supplemental oral olanzapine or another dosing strategy may be necessary to maintain adequate therapeutic response during the first few injection cycles...
  77. ncbi request reprint Emerging drugs for schizophrenia
    Ofer Agid
    Centre for Addiction and Mental Health, Schizophrenia Program, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, Ontario M5T 1R8, Canada
    Expert Opin Emerg Drugs 13:479-95. 2008
    ..As the dust settles on this period and substantial data, as well as practical prescribing experience, are available, we examine what has been gained and what can be learned...
  78. ncbi request reprint Treatment response to olanzapine and haloperidol and its association with dopamine D receptor occupancy in first-episode psychosis
    Robert B Zipursky
    Department of Psychiatry, University of Toronto, Ontario
    Can J Psychiatry 50:462-9. 2005
    ..We undertook this study to determine whether response to the atypical antipsychotic olanzapine occurs at lower levels of D2 receptor occupancy...
  79. ncbi request reprint Differential effects of within-day continuous vs. transient dopamine D2 receptor occupancy in the development of vacuous chewing movements (VCMs) in rats
    Peter Turrone
    Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada
    Neuropsychopharmacology 28:1433-9. 2003
    ..These findings support the contention that D(2) occupancy levels induced by chronic HAL must be high and sustained through the day before significant risk of VCMs, and perhaps also TD, emerges...
  80. ncbi request reprint Effect of acute antipsychotic administration on dopamine synthesis in rodents and human subjects using 6-[18F]-L-m-tyrosine
    David Mamo
    Department of Psychiatry, University of Toronto, Canada
    Synapse 52:153-62. 2004
    ..Our results suggest that 6-[18F]-L-m-tyrosine PET may not be a useful tool in the study of the effect of antipsychotics on dopamine synthesis in human subjects...
  81. ncbi request reprint A putative animal model of the "prodromal" state of schizophrenia
    Catherine C Tenn
    Schizophrenia PET Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto Canada
    Biol Psychiatry 57:586-93. 2005
    ..The objective of this study was to develop a putative model of the prodrome and study the effects of medications on it...
  82. ncbi request reprint Contrasting loxapine to its isomer isoloxapine--the critical role of in vivo D2 blockade in determining atypicality
    Sridhar Natesan
    Schizophrenia PET program, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada, M5T 1R8
    Schizophr Res 77:189-99. 2005
    ..The purpose of this study was to systematically compare the two drugs in in vitro and in vivo animal models, and to understand mechanisms underlying their differential typical/atypical profiles...
  83. ncbi request reprint Amoxapine as an atypical antipsychotic: a comparative study vs risperidone
    Rogelio Apiquian
    Department of Psychiatry, National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Av Insurgentes Sur 3877, Mexico City, 14296 Mexico
    Neuropsychopharmacology 30:2236-44. 2005
    ..Since amoxapine is off-patent, it may be a valuable low-cost alternative to new atypical antipsychotics, particularly in low-income countries where the majority of the patients are still treated with typical antipsychotics...
  84. ncbi request reprint A PET study of dopamine D2 and serotonin 5-HT2 receptor occupancy in patients with schizophrenia treated with therapeutic doses of ziprasidone
    David Mamo
    Department of Psychiatry, University of Toronto, Montreal, Canada
    Am J Psychiatry 161:818-25. 2004
    ..The affinity of ziprasidone for these receptors in vivo in patients was examined in a positron emission tomography (PET) study...
  85. ncbi request reprint Equivalent occupancy of dopamine D1 and D2 receptors with clozapine: differentiation from other atypical antipsychotics
    Johannes Tauscher
    University of Toronto Department of Psychiatry, Schizophrenia Program
    Am J Psychiatry 161:1620-5. 2004
    ....
  86. ncbi request reprint Linking animal models of psychosis to computational models of dopamine function
    Andrew J Smith
    Bentley Heath, Solihull, West Midlands, UK
    Neuropsychopharmacology 32:54-66. 2007
    ..The model's primary contribution is to link dopamine neuron firing, receptor manipulation, and behavior within a common formal framework that may offer insights into clinical observations...
  87. ncbi request reprint Blockade of 5-HT2a receptors reduces haloperidol-induced attenuation of reward
    Faïza Benaliouad
    Centre de Recherche Fernand Seguin, Hopital Louis H Lafontaine, Montreal, QC, Canada
    Neuropsychopharmacology 32:551-61. 2007
    ....
  88. ncbi request reprint Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action
    Shitij Kapur
    Department of Psychiatry, University of Toronto, Toronto M5S 3H6, Canada
    Neuroreport 13:831-5. 2002
    ..The implications for the design of future antipsychotics is discussed...
  89. ncbi request reprint Relation between cortical dopamine D(2) receptor occupancy and suppression of conditioned avoidance response in non-human primate
    Akihiro Takano
    Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan
    Psychiatry Clin Neurosci 58:330-2. 2004
    ..It is suggested that the threshold level of cortical dopamine D(2) receptor occupancy for the suppression of CAR is demonstrated in the present study...
  90. ncbi request reprint Amoxapine as an antipsychotic: comparative study versus haloperidol
    Imran B Chaudhry
    University of Manchester, Manchester, UK
    J Clin Psychopharmacol 27:575-81. 2007
    ..However, it did not prove to have fewer extrapyramidal side effects than haloperidol, possibly because the baseline scores were very low...
  91. ncbi request reprint A model of anticholinergic activity of atypical antipsychotic medications
    Marci L Chew
    Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA
    Schizophr Res 88:63-72. 2006
    ..However, it is difficult with the available data to predict the likelihood of anticholinergic effects occurring with various doses of an atypical antipsychotic...
  92. ncbi request reprint Clozapine can induce high dopamine D(2) receptor occupancy in vivo
    Tetsuya Suhara
    Brain Imaging Project, National Institute of Radiological Sciences, Chiba, Japan
    Psychopharmacology (Berl) 160:107-12. 2002
    ..Furthermore, even at maximum occupancy, 70% is not exceeded. Several mechanisms have been proposed as explanations for this low D(2) receptor occupancy, but clear evidence is limited...