Baseline and Amphetamine-Stimulated Dopamine Activity Are Related in Drug-Naïve Schizophrenic Subjects
Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in dr...
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| Published in | Biological psychiatry (1969) Vol. 65; no. 12; pp. 1091 - 1093 |
|---|---|
| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
New York, NY
Elsevier Inc
15.06.2009
Elsevier |
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| Online Access | Get full text |
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| Abstract | Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC).
Six drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP
ND) for striatal D2 at baseline, after amphetamine administration and after DA depletion.
Amphetamine induced decrease in BP
ND was positively correlated with BP
ND increase after DA depletion in SCZ (
p = .02) but not in HC (
p = .44). Additionally, both were significantly increased.
In drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the α-methyl-para-tyrosine (αMPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity. |
|---|---|
| AbstractList | BackgroundPrevious studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC). MethodsSix drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP ND) for striatal D2 at baseline, after amphetamine administration and after DA depletion. ResultsAmphetamine induced decrease in BP ND was positively correlated with BP ND increase after DA depletion in SCZ ( p = .02) but not in HC ( p = .44). Additionally, both were significantly increased. ConclusionsIn drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the α-methyl-para-tyrosine (αMPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity. Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC).BACKGROUNDPrevious studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC).Six drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP(ND)) for striatal D2 at baseline, after amphetamine administration and after DA depletion.METHODSSix drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP(ND)) for striatal D2 at baseline, after amphetamine administration and after DA depletion.Amphetamine induced decrease in BP(ND) was positively correlated with BP(ND) increase after DA depletion in SCZ (p = .02) but not in HC (p = .44). Additionally, both were significantly increased.RESULTSAmphetamine induced decrease in BP(ND) was positively correlated with BP(ND) increase after DA depletion in SCZ (p = .02) but not in HC (p = .44). Additionally, both were significantly increased.In drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the alpha-methyl-para-tyrosine (alpha MPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity.CONCLUSIONSIn drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the alpha-methyl-para-tyrosine (alpha MPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity. Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC). Six drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP ND) for striatal D2 at baseline, after amphetamine administration and after DA depletion. Amphetamine induced decrease in BP ND was positively correlated with BP ND increase after DA depletion in SCZ ( p = .02) but not in HC ( p = .44). Additionally, both were significantly increased. In drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the α-methyl-para-tyrosine (αMPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity. Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of da release in drug-naive patients with schizophrenia (SCZ) and matched healthy control subjects (HC). Methods - Six drug-naive SCZ and eight HC underwent single- photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-+AFs-123I+AF0-iodo-2-hydroxy-6-methoxy-N-+AFs-(1-ethyl-2 - pyrrolidinyl)methyl+AF0-benzamide (+AFs-123I+AF0-IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP+AFs-sub+AF0-ND) for striatal D2 at baseline, after amphetamine administration and after da depletion. Results - Amphetamine induced decrease in BP+AFs-sub+AF0-ND was positively correlated with BP+AFs-sub+AF0-ND increase after da depletion in SCZ (p +AD0-.02) but not in HC (p +AD0-.44). Additionally, both were significantly increased. Conclusions - In drug-naive patients with schizophrenia but not in control subjects, stimulated and baseline da release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic da release, measured with the +AFs-alpha+AF0--methyl-para- tyrosine (+AFs-alpha+AF0-MPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain da cells activity. Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in patients with schizophrenia compared with control subjects. We report here on the relationship between these two aspects of DA release in drug-naïve patients with schizophrenia (SCZ) and matched healthy control subjects (HC). Six drug-naïve SCZ and eight HC underwent single-photon emission computed tomography (SPECT) scans after bolus followed by constant infusion of (S)-(-)-3-[123I]iodo-2-hydroxy-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]benzamide ([123I]IBZM) under three conditions to determine the equilibrium specific to non-displaceable binding potential (BP(ND)) for striatal D2 at baseline, after amphetamine administration and after DA depletion. Amphetamine induced decrease in BP(ND) was positively correlated with BP(ND) increase after DA depletion in SCZ (p = .02) but not in HC (p = .44). Additionally, both were significantly increased. In drug-naïve patients with schizophrenia but not in control subjects, stimulated and baseline DA release are both increased and positively correlated. At the neuronal level this association suggests that capacity for storage in presynaptic terminals, measured with the amphetamine paradigm, and baseline intrasynaptic DA release, measured with the alpha-methyl-para-tyrosine (alpha MPT) paradigm, are associated in schizophrenia, both consistent with increased midbrain DA cells activity. |
| Author | van de Giessen, Elsmarieke Laruelle, Marc Abi-Dargham, Anissa Kegeles, Lawrence S. Slifstein, Mark |
| Author_xml | – sequence: 1 givenname: Anissa surname: Abi-Dargham fullname: Abi-Dargham, Anissa email: aa324@columbia.edu organization: Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, New York – sequence: 2 givenname: Elsmarieke surname: van de Giessen fullname: van de Giessen, Elsmarieke organization: Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, New York – sequence: 3 givenname: Mark surname: Slifstein fullname: Slifstein, Mark organization: Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, New York – sequence: 4 givenname: Lawrence S. surname: Kegeles fullname: Kegeles, Lawrence S. organization: Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, New York – sequence: 5 givenname: Marc surname: Laruelle fullname: Laruelle, Marc organization: Department of Psychiatry, New York State Psychiatric Institute, Columbia University College of Physicians and Surgeons, New York, New York |
| BackLink | http://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21561439$$DView record in Pascal Francis https://www.ncbi.nlm.nih.gov/pubmed/19167701$$D View this record in MEDLINE/PubMed |
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| Keywords | amphetamine D2 receptor schizophrenia dopamine SPECT α-MPT Amphetamine derivatives Radionuclide study Human Dopamine CNS stimulant Psychotropic Schizophrenia Single photon emission tomography Catecholamine Photon Psychosis D2 Dopamine receptor Neurotransmitter Amfetamine |
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| Snippet | Previous studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2 receptors in... BackgroundPrevious studies demonstrated increased striatal dopamine (DA) release after amphetamine challenge and increased striatal baseline occupancy of D2... |
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| SubjectTerms | Adult Adult and adolescent clinical studies alpha-Methyltyrosine amphetamine Amphetamine - pharmacology Benzamides Biological and medical sciences D2 receptor dopamine Dopamine - metabolism Dopamine Uptake Inhibitors - pharmacology Enzyme Inhibitors Female Humans Image Processing, Computer-Assisted Male Medical sciences Neostriatum - diagnostic imaging Neostriatum - metabolism Neuropharmacology Pharmacology. Drug treatments Psychiatric/Mental Health Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease) Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychopharmacology Psychoses Pyrrolidines Radiopharmaceuticals Receptors, Dopamine D2 - drug effects Receptors, Dopamine D2 - metabolism Schizophrenia Schizophrenia - diagnostic imaging Schizophrenia - metabolism SPECT Tomography, Emission-Computed, Single-Photon Young Adult α-MPT |
| Title | Baseline and Amphetamine-Stimulated Dopamine Activity Are Related in Drug-Naïve Schizophrenic Subjects |
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