Cited by 1,154Schizophrenia research and treatmentNeurotransmitter Receptor Influence on BehaviorParkinson's Disease Mechanisms and Treatments

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Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method

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Breier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., Pickar, D.·1997·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.94.6.2569PMC PMC20129

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Abstract

A major line of evidence that supports the hypothesis of dopamine overactivity in schizophrenia is the psychomimetic potential of agents such as amphetamine that stimulate dopamine outflow. A novel brain imaging method provides an indirect measure of in vivo synaptic dopamine concentration by quantifying the change in dopamine receptor radiotracer binding produced by agents that alter dopamine release but do not themselves bind to dopamine receptors. The purpose of this investigation is (i) to determine the sensitivity (i.e., amount of dopamine reflected in radiotracer binding changes) of this method by examining the relationship between amphetamine-induced changes in simultaneously derived striatal extracellular dopamine levels with in vivo microdialysis and striatal binding levels with the dopamine D2/D3 positron-emission tomography radioligand [11C]raclopride in nonhuman primates, and (ii) to test the hypothesis of elevated amphetamine-induced synaptic dopamine levels in schizophrenia. In the nonhuman primate study (n = 4), doubling the amphetamine dose produced a doubling in [11C]raclopride specific binding reductions. In addition, the ratio of percent mean dopamine increase to percent mean striatal binding reduction for amphetamine (0.2 mg/kg) was 44:1, demonstrating that relatively small binding changes reflect large changes in dopamine outflow. In the clinical study, patients with schizophrenia (n = 11) compared with healthy volunteers (n = 12) had significantly greate…

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Background
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Method
Tracer Kinetic Modeling in PET
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“The alternative study design is to administer the tracer as a combined bolus plus continuous infusion (B/I) to measure short-term changes in free receptor concentration [101, 147, 148].”
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Background
Impact of D2 Receptor Internalization on Binding Affinity of Neuroimaging Radiotracers
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BackgroundResult
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Background
A Simple Method to Measure Baseline Occupancy of Neostriatal Dopamine D2 Receptors by Dopamine In Vivo in Healthy Subjects
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Self-citation
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BackgroundMethod
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Result
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Result
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“Data are expressed as the mean and SD.”
BackgroundMethod
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Self-citation
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Background
PET study of the effects of valproate on dopamine D(2) receptors in neuroleptic- and mood-stabilizer-naive patients with nonpsychotic mania.
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“This model has been supported recently by in vivo neuroimaging studies showing enhanced subcortical dopamine release in response to amphetamine challenge in individuals with schizophrenia (Abi-Dargham et al, 1998; Breier et al, 1997; Laruelle, 1998; Laruelle et al, 1996, 1999).”
Background
Dopamine modulates mitochondrial function in viable SH-SY5Y cells possibly via its interaction with complex I: Relevance to dopamine pathology in schizophrenia
Brenner-Lavie, H., Klein, E., Zuk, R., Gazawi, H., Ljubuncić, P., & Ben‐Shachar, D. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.10.006 · Cited by 79
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Background
Fibroblast growth factor receptor signaling affects development and function of dopamine neurons – inhibition results in a schizophrenia‐like syndrome in transgenic mice
Klejbor, I., Myers, J. M., Hausknecht, K., Corso, T. D., Gambino, A. S., Moryś, J., Maher, P., Hard, R., Richards, J. C., Stachowiak, E., et al. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03754.x · Cited by 76
“2002; Wong and Van Tol 2003) and are normalized by treatment with clozapine or classical neuroleptics (Laruelle et al. 1996; Breier et al. 1997; Carson et al. 1997).”
Background
Imaging the Dopamine System with In Vivo [11C]raclopride Displacement Studies: Understanding the True Mechanism
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“For example, the DA hypothesis of schizophrenia has experienced a renewal of interest from the observation that patients with schizophrenia show an abnormally high level and release of DA [1, 2].”
Significant decreases in frontal and temporal [11C]-raclopride binding after THC challenge
Stokes, P. R. A., Egerton, A., Watson, B., Reid, A., Breen, G., Lingford-Hughes, A., Nutt, D., & Mehta, M. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.04.274 · Cited by 75
“…correlation between decrease in striatal [11C]-raclopride binding and increase in dopamine release in dual microdialysis PET studies in animals (Breier et al., 1997; Endres et al., 1997; Schiffer et al., 2006), and studies in man demonstrating decreases in [11C]-raclopride binding following…”
Influential
Delineating the psychic structure of substance abuse and addictions: should anxiety, mood and impulse-control dysregulation be included?
Pani, P., Maremmani, I., Trogu, E., Gessa, G., Ruiz, P. P., & Akiskal, H. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2009.06.012 · Cited by 75
Positron Emission Tomography in Schizophrenia: A New Perspective
Patel, N., Vyas, N. S., Puri, B. K., Nijran, K. S., & AL-NAHHAS, A. M. (2010) · Journal of Nuclear Medicine · doi:10.2967/jnumed.109.066076 · Cited by 71
“Amphetaminelike drugs cause an increase in striatal dopamine in schizophrenia (70).”
Background
Targeting Prefrontal Cortical Dopamine D1 and N-Methyl-D-Aspartate Receptor Interactions in Schizophrenia Treatment
Yang, C. R., & Chen, L. (2005) · The Neuroscientist · doi:10.1177/1073858405279692 · Cited by 65
Associated alterations of striatal dopamine D2/D3 receptor and transporter binding in drug-naive patients with schizophrenia: a dual-isotope SPECT study.
Yang, Y.-K., Yu, L., Yeh, T.-L., Chiu, N.-T., Chen, P., & Lee, H. I. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.8.1496 · Cited by 75
Attenuated extracellular dopamine levels after stress and amphetamine in the nucleus accumbens of rats with neonatal ventral hippocampal damage
Lillrank, S., Lipska, B., Kolachana, B., & Weinberger, D. R. (1999) · Journal of neural transmission · doi:10.1007/s007020050150 · Cited by 75
“In contrast, patients with schizophrenia manifest decreased radioligand binding in the striatum following systemic AMPH administration, suggesting increased DA release (Laruelle et al., 1996; Breier et al., 1997).”
Self-citation
Serotonin depletion in the dorsal and ventral hippocampus: effects on locomotor hyperactivity, prepulse inhibition and learning and memory.
Adams, W. K., Kusljic, S., & van den Buuse, M. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.06.035 · Cited by 74
Tiagabine Increases [11C]flumazenil Binding in Cortical Brain Regions in Healthy Control Subjects
Frankle, W. G., Cho, R. Y., Narendran, R., Mason, N. S., Vora, S., Litschge, M. Y., Price, J. C., Lewis, D. A., & Mathis, C. A. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.104 · Cited by 79
“These studies have yielded important insights into the pathophysiology of mental illnesses such as schizophrenia and substance abuse (Laruelle et al, 1996; Breier et al, 1997; Volkow et al, 1997; Abi-Dargham et al, 2000; Martinez et al, 2005, 2007).”
Cognitive deficit in schizophrenia and its neurochemical basis
Breier, A. (1999) · British Journal of Psychiatry · doi:10.1192/s0007125000293604 · Cited by 74
Self-citation
Drugs for psychosis and mood: unique actions at D3, D2, and D1 dopamine receptor subtypes
Stahl, S. M. (2017) · CNS Spectrums · doi:10.1017/s1092852917000608 · Cited by 235
Regional dopamine synthesis in patients with schizophrenia using L-[β-11C]DOPA PET
Nozaki, S., Kato, M., Takano, H., Ito, H., Takahashi, H., Arakawa, R., Okumura, M., Fujimura, Y., Matsumoto, R., Ota, M., et al. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2008.11.006 · Cited by 74
“Regarding intrasynaptic function, striatal dopamine release was reported to be enhanced in schizophrenia (Breier et al., 1997; Laruelle et al., 1996).”
Effect of amphetamine on [18F]fallypride in vivo binding to D2 receptors in striatal and extrastriatal regions of the primate brain: Single bolus and bolus plus constant infusion studies
Slifstein, M., Narendran, R., Hwang, D., Sudo, Y., Talbot, P. S., Huang, Y. H., & Laruelle, M. A. (2004) · Synapse · doi:10.1002/syn.20062 · Cited by 66
“This condition has been demonstrated with [11C]raclopride and [123I]IBZM (Laruelle et al., 1995, 1997; Breier et al., 1997; Carson et al., 1997; Endres et al., 1997; Kegeles et al., 1999; Villemagne et al., 1999; Martinez et al., 2003).”
BackgroundMethodResultInfluential
Dopamine mediation of positive reinforcing effects of amphetamine in stimulant naı̈ve healthy volunteers: results from a large cohort
Abi‐Dargham, A., Kegeles, L. S., Martínez, D., Innis, R. B., & Laruelle, M. A. (2003) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2003.08.007 · Cited by 72
“In nonhuman primates, the magnitude of this reduction is related to the amphetamine-induced increase in extracellular DA measured with microdialysis (Breier et al., 1997; Laruelle et al., 1997).”
Background
Antipsychotic drugs, dopamine receptors, and schizophrenia
Seeman, P. (2001) · Clinical Neuroscience Research · doi:10.1016/s1566-2772(00)00007-4 · Cited by 73
Prenatal inflammation-induced hypoferremia alters dopamine function in the adult offspring in rat: relevance for schizophrenia
Aguilar-Valles, A., Flores, C., & Luheshi, G. N. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010967 · Cited by 72
“symptoms of the disorder [81–84].”
Imaging Agonist-Induced D2/D3 Receptor Desensitization and Internalization In Vivo with PET/fMRI
Sander, C. Y. M., Hooker, J. M., Catana, C., Rosen, B. R., & Mandeville, J. B. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.296 · Cited by 66
“This model provides a valid explanation for some experimental data: for certain PET ligands, decreases in binding potential accompany increases in DA concentration, as measured by microdialysis (Breier et al, 1997; Laruelle et al, 1997).”
Method
The dopamine D4 receptors and mechanisms of antipsychotic atypicality
Wong, A. H. C., & Tol, H. H. M. V. (2003) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2003.09.005 · Cited by 68
VMAT2 binding is elevated in dopa‐responsive dystonia: Visualizing empty vesicles by PET
de la Fuente-Fernández, R., Furtado, S., Guttman, M., Furukawa, Y., Lee, C. S., Calne, D., Ruth, T. J., & Stoessl, A. (2003) · Synapse · doi:10.1002/syn.10199 · Cited by 72
“The changes induced by the acute levodopa test were of the same magnitude as those reported in normal volunteers after amphetamine administration (Breier et al., 1997), and substantially greater than those obtained after oral levodopa administration in patients with Parkinson’s disease of almost…”
Result
Effect of a haloperidol challenge on regional brain metabolism in neuroleptic-responsive and nonresponsive schizophrenic patients.
Bartlett, E., Brodie, J., Simkowitz, P., Schlösser, R., Dewey, S., Lindenmayer, J., Rusinek, H., Wolkin, A., Cancro, R., & Schiffer, W. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.3.337 · Cited by 72
“(22) have confirmed that in comparison with control subjects, schizophrenic subjects do not show elevated synaptic dopamine concentrations in vivo but do show elevated presynaptic dopamine reserves that can be mobilized with amphetamine.”
Background
Presynaptic Regulation of Dopamine Transmission in Schizophrenia
Lyon, G. J., Abi‐Dargham, A., Moore, H. M., Lieberman, J. A., Javitch, J. A., & Sulzer, D. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbp010 · Cited by 71
Catching Up on Schizophrenia
Lewis, D. A., & Lieberman, J. A. (2000) · Neuron · doi:10.1016/s0896-6273(00)00111-2 · Cited by 833
Allostatic Load as a Tool for Monitoring Physiological Dysregulations and Comorbidities in Patients with Severe Mental Illnesses
Bízik, G., Picard, M. A., Nijjar, R., Tourjman, V., McEwen, B. S., LUPIEN, S. J., & Juster, R. (2013) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000012 · Cited by 76
Neurophysiological and neurochemical animal models of schizophrenia: Focus on glutamate☆
Bickel, S., & Javitt, D. C. (2009) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.05.005 · Cited by 68
“In primate studies, the degree of radiolabel displacement observed in clinical studies – 10–38% – corresponds to increases in striatal dopamine levels of between 400 and 1500% [13,69,66].”
Background
Cerebral glucose utilization and platelet mitochondrial complex I activity in schizophrenia: A FDG-PET study
Ben‐Shachar, D., Bonne, O. B., Chisin, R., Klein, E., Lester, H., Aharon‐Peretz, J., Yona, I., & Freedman, N. (2007) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2006.12.025 · Cited by 72
Cortical acetylcholine, reality distortion, schizophrenia, and Lewy Body Dementia: too much or too little cortical acetylcholine?
Sarter, M., & Bruno, J. (1998) · Brain and Cognition · doi:10.1006/brcg.1998.1035 · Cited by 70
“…this discussion, an increased dopaminergic transmission in mesolimbic areas, specifically the nucleus accumbens, continues to be considered a cardinal component in the aberrant neuronal mechanisms which are normalized by antipsychotic drugs (Breier et al., 1997; Grace, Bunney, Moore, & Todd, 1997).”
Background
Application of cross-species PET imaging to assess neurotransmitter release in brain
Finnema, S. J., Scheinin, M., Shahid, M., Lehto, J., Borroni, E., Bang‐Andersen, B., Sallinen, J., Wong, E. H. F., Farde, L., Halldin, C., et al. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3938-6 · Cited by 82
“A m ph et am in e (0 .5 m g/ kg p. o. ,3 h pr io r) vs . ba se lin e H um an (n = 14 ) B B P N D ↓8 –1 3 % in va ri ou s re gi on s (C ro pl ey et al .2 00 8) general, clinically applicable doses of amphetamine have reduced [11C]raclopride binding in the human striatum by up to 20 %, which is a sufficient effect size…”
BackgroundInfluential
Decreased Prefrontal Cortical Dopamine Transmission in Alcoholism
Narendran, R., Mason, N. S., Paris, J., Himes, M. L., Douaihy, A. B., & Frankle, W. G. (2014) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2014.13121581 · Cited by 69
“extracellular dopamine concentration induced by the challenge (15).”
Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study
Selvaraj, S., Turkheimer, F., Rosso, L., Faulkner, P., Mouchlianitis, E., Roiser, J., Mcguire, P., Cowen, P., & Howes, O. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.78 · Cited by 69
Amphetamine sensitization in rats as an animal model of schizophrenia.
Peleg-Raibstein, D., Knuesel, I., & Feldon, J. (2008) · Behavioural Brain Research · doi:10.1016/j.bbr.2008.03.037 · Cited by 69
“Neuroimaging studies using single photon emission tomography (SPECT) and positron emission tomography (PET) have confirmed the dysregulation of striatal dopamine function in schizophrenia patients expressed an enhanced displacement of dopamine D2 receptor ligands [1,9,28].”
Background
Clozapine, quetiapine and olanzapine among addicted schizophrenic patients: towards testable hypotheses
Potvin, S., Stip, E., & Roy, J. (2003) · International Clinical Psychopharmacology · doi:10.1097/01.yic.0000063501.97247.38 · Cited by 69
“…(Lauer et al., 2001); (ix) as measured by PET or single-photon emission computed tomography (SPECT), the release of dopamine in the striatum, after the administration of amphetamines, is greater in schizophrenics than in normal subjects (Breier et al., 1997; Laruelle and Abi-Dargham, 1999).”
Background
Does cannabis affect dopaminergic signaling in the human brain? A systematic review of evidence to date
Sami, M. B., Rabiner, E. A., & Bhattacharyya, S. (2015) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2015.03.011 · Cited by 62
“It has been argued that the effect-size is modest and less detectable in humans, with a demonstrated ratio of 40:1 between increase in dopamine and reductions in raclopride (Breier et al., 1997; Laruelle et al., 1997).”
Imaging extrastriatal dopamine D(2) receptor occupancy by endogenous dopamine in healthy humans.
Fujita, M., Verhoeff, N., Varrone, A., Zoghbi, S., Baldwin, R., Jatlow, P., Anderson, G. M., Seibyl, J., & Innis, R. B. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(99)00817-1 · Cited by 68
[Glutamatergic hypothesis of schizophrenia].
Bressan, R., & Pilowsky, L. (2003) · Revista Brasileira de Psiquiatria · doi:10.1590/s1516-44462003000300011 · Cited by 67
“Dois outros estudos posteriores confirmaram estes achados em pacientes esquizofrênicos.(41,42) Abi-Darghan et al(42) mostraram que a liberação de dopamina foi mais intensa nos pacientes que estavam na fase de exacerbação dos sintomas psicóticos, sugerindo que este fenômeno está diretamente implicado na ocorrência de s…”
Background
The schizophrenia ketamine challenge study debate.
Carpenter, W. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00194-8 · Cited by 67
The Dopamine Dysfunction in Schizophrenia Revisited: New Insights into Topography and Course
Kuepper, R., Skinbjerg, M., & Abi‐Dargham, A. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25761-2_1 · Cited by 65
“The results of a subsequent PET study using [C]raclopride as radiotracer were in line with these observations (Breier et al. 1997): The schizophrenia group showed greater amphetamine-induced decreases in [C]raclopride binding compared to controls, indicative of greater amphetamine-induced release of endogenous DA.”
Result
Birth insult increases amphetamine-induced behavioral responses in the adult rat
El‐Khodor, B. F., & Boksa, P. (1998) · Neuroscience · doi:10.1016/s0306-4522(98)00194-8 · Cited by 69
Imaging-Based Neurochemistry in Schizophrenia: A Systematic Review and Implications for Dysfunctional Long-Term Potentiation
Salavati, B., Rajji, T. K., Price, R., Sun, Y., Graff‐Guerrero, A., & Daskalakis, Z. J. (2014) · Schizophrenia Bulletin · doi:10.1093/schbul/sbu132 · Cited by 71
Dopaminergic synapses in the caudate of subjects with schizophrenia: relationship to treatment response
Roberts, R. C., Roche, J. K., Conley, R. R., & Lahti, A. C. (2009) · Synapse · doi:10.1002/syn.20623 · Cited by 65
“…displays augmentation of presynaptic dopamine function, indicating an increase in dopamine synthesis capacity and/or an increase in presynaptic dopamine stores (Abi-Dargham et al., 1998, 2000; Breier et al., 1997; DaoCastellana et al., 1997; Hietala et al., 1995, 1999; Laruelle et al., 1996, 1999).”
Background
Amphetamine-induced disruption of prepulse inhibition in mice with reduced NMDA receptor function.
Moy, S., Perez, A., Koller, B., & Duncan, G. (2006) · Brain Research · doi:10.1016/j.brainres.2006.03.073 · Cited by 65
Nicotine-Induced Dopamine Release in Primates Measured with [11C]Raclopride PET
Marenco, S., Carson, R. E., Berman, K. F., Herscovitch, P., & Weinberger, D. R. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300287 · Cited by 62
“Neuropsychopharmacology (2004) 29, 259–268, advance online publication, 3 December 2003; doi:10.1038/sj.npp.1300287 Keywords: nicotine; dopamine release; primates; anesthesia; schizophrenia”
BackgroundMethodInfluentialSelf-citation
NMDA antagonist effects on striatal dopamine release: Microdialysis studies in awake monkeys
Adams, B. W., Bradberry, C., & Moghaddam, B. (2002) · Synapse · doi:10.1002/syn.1114 · Cited by 65
“Although it is difficult to determine “comparable” doses between different species, it is important to emphasize that the doses of amphetamine used here (0.1 and 0.4 mg/kg) are in the range of doses used in clinical studies (Breier et al., 1997; Kegeles et al., 2000; Laruelle et al., 1997).”
Influential
Continuous Phencyclidine Treatment Induces Schizophrenia-Like Hyperreactivity of Striatal Dopamine Release
Balla, A., Koneru, R., Smiley, J., Sershen, H., & Javitt, D. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00230-5 · Cited by 65
“One of the hallmarks of schizophrenia is an increase in the responsiveness of subcortical dopamine release to amphetamine administration, which has been demonstrated repeatedly in vivo in unmedicated subjects (Breier et al. 1997; Abi-Dargham et al. 1998; Laruelle et al. 1996).”
Background
Dopaminergic abnormalities following traumatic brain injury
Jenkins, P., Simoni, S. D., Bourke, N., Fleminger, J., Scott, G. P. T., Towey, D., Svensson, W., Khan, S., Patel, M. C., Greenwood, R., et al. (2018) · Brain : a journal of neurology · doi:10.1093/brain/awx357 · Cited by 64
Expression of 5-HT2A receptors in prefrontal cortex pyramidal neurons projecting to nucleus accumbens. Potential relevance for atypical antipsychotic action.
Mocci, G., Jiménez-Sánchez, L., Adell, A., Cortés, R., & Artigas, F. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.10.021 · Cited by 64
“Indeed, the mesolimbic dopaminergic hyperactivity responsible for psychotic symptoms (Breier et al., 1997; Laruelle et al., 1996) likely results in alterations of the information processing along basal ganglia circuits.”
Influential
Mice lacking the schizophrenia-associated protein FEZ1 manifest hyperactivity and enhanced responsiveness to psychostimulants.
Sakae, N., Yamasaki, N., Kitaichi, K., Fukuda, T., Yamada, M., Yoshikawa, H., Hiranita, T., Tatsumi, Y., Kira, J., Yamamoto, T., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddn215 · Cited by 64
Oral D‐amphetamine causes prolonged displacement of [11C]raclopride as measured by PET
Cárdenas, L., Houle, S., Kapur, S., & Busto, U. E. (2004) · Synapse · doi:10.1002/syn.10282 · Cited by 63
“The magnitude of displacement observed at 2 h postdrug (13.3% 5) is comparable to that reported in humans when a single dose of 0.2 mg/kg of D-amphetamine was administered i.v. (15.5% 1.8) (Breier et al., 1997).”
BackgroundMethodResultInfluential
An Overview of the Association between Schizotypy and Dopamine
Mohr, C., & Ettinger, U. (2014) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2014.00184 · Cited by 63

Authors: Breier, A., Su, T.-P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., Weinberger, D. R., Weisenfeld, N., Malhotra, A. K., Eckelman, W. C., & Pickar, D.
Affiliations: National Institutes of Health (US)
ORCID: Su, T.-P.
Saunders, R.
Carson, R. E.
Kolachana, B. S.
de Bartolomeis, A.
Weinberger, D. R.
Malhotra, A. K.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 1997-03-18
Volume: 94
Issue: 6
Pages: 2569-2574
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.94.6.2569
PMC: PMC20129
OpenAlex: W2150760506
Cited by: 1,154
References: 43
Citations by year: 2026: 8 · 2025: 12 · 2024: 19 · 2023: 9 · 2022: 17 · 2021: 22 · 2020: 20 · 2019: 26 · 2018: 29 · 2017: 27 · 2016: 34 · 2015: 35 · 2014: 44 · 2013: 51 · 2012: 54
FWCI: 36.57
Type: journal article
Language: en
Open access: green
europepmc.org
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Keywords: schizophrenia, synaptic dopamine, amphetamine, [11C]raclopride, striatum, dopamine release, microdialysis, non-human primates
MeSH terms: Amphetamine, Animals, Carbon Radioisotopes, Corpus Striatum, Dopamine, Humans, Macaca mulatta, Reference Values, Regression Analysis, Salicylamides, Schizophrenia, Synapses, Tomography, Emission-Computed, Microdialysis, Raclopride

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Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: Evidence from a novel positron emission tomography method

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