Presynaptic dopaminergic function in the striatum of schizophrenic patients

Dao-Castellana, M H; Paillère-Martinot, Marie-Laure; Hantraye, Philippe; Attar-Levy, D.; Rémy, Philippe; Crouzel, C.; Artiges, Éric; Féline, A.; Syrota, A.; Martinot, Jean‐Luc

doi:10.1016/s0920-9964(96)00102-8

Cited by 151 publications

(59 citation statements)

References 32 publications

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“…On the other hand, studies in anesthetized cats , anesthetized nonhuman primates (Narendran et al, 2004;Seneca et al, 2006), and awake humans showed greater displacement with an agonist radiotracer ( high and/or D 3 is indeed present in acute psychotic state in schizophrenia, but this may be masked by the presence of abnormal high levels of dopamine in the synaptic cleft. The abnormal high levels of dopamine in psychosis has been indirectly shown after an amphetamine challenge (AbiDargham et al, 1998), but the dopamine striatal synthesis capacity has reliably been found higher than in controls (Dao-Castellana et al, 1997;Hietala et al, 1999;Huttunen et al, 2007;Reith et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

The Dopamine D2 Receptors in High-Affinity State and D3 Receptors in Schizophrenia: A Clinical [11C]-(+)-PHNO PET Study

Graff‐Guerrero

Mizrahi

Agid

et al. 2008

Neuropsychopharmacol

102

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The dopamine D 2 receptors exist in two states: a high-affinity state (D 2 high ) that is linked to second messenger systems, is responsible for functional effects, and exhibits high affinity for agonists; and a low-affinity state that is functionally inert and exhibits lower affinity for agonists. The dopamine D 3 receptors have high-affinity for agonist (eg dopamine) and the existence of the two affinity states is controversial. Although preclinical studies in animal models of psychosis have shown a selective increase of D 2 high as the common pathway to psychosis, the D 3 has been suggested to be involved in the pathophysiology of psychosis. We report the first study of the D 2 high and D 3 in schizophrenia using the novel PET radiotracer, [ 11 C]-( + )-PHNO. We recruited 13 patients with schizophrenia-spectrum disorder amidst an acute psychotic episode, drug free for at least 2 weeks, and 13 age-sex-matched healthy controls. The binding potential nodisplaceable (BP ND ) was examine in the main regions of interest (caudate, putamen, ventral striatum, globus pallidus, substantia nigra, and anterior thalamus) and in a voxel-wise analysis. The BP ND between patients and controls was not different in any of the regions. The voxel-wise analysis did not reveal any difference and no correlations were found between the BP ND and positive and negative syndrome scale subscales. Our results do not find support for the hypothesis linking psychosis to a selective increase in D 2 high and/or D 3 in schizophrenia. 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.

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Section: Discussionmentioning

confidence: 99%

The Dopamine D2 Receptors in High-Affinity State and D3 Receptors in Schizophrenia: A Clinical [11C]-(+)-PHNO PET Study

Graff‐Guerrero

Mizrahi

Agid

et al. 2008

Neuropsychopharmacol

102

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“…25 Consistent with these data, DA striatal synthesis capacity has been found to be higher in patients with schizophrenia than in controls in most studies. [57][58][59][60] More recently, Howes and colleagues 61 also reported increased DA synthesis capacity in both CHR individuals and patients with schizophrenia, which correlated with conversion to schizophrenia. 62 In the absence of restingstate (baseline) BP ND data, or following a depletion paradigm (i.e., α-methyl partyrosine), it is not possible to ascertain whether the lack of difference among the groups is owing to different levels of baseline DA or to release during the cognitive task.…”

Section: Limitationsmentioning

confidence: 93%

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Suridjan

Rusjan²,

Addington³

et al. 2013

J Psychiatry Neurosci

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“…First, four of five imaging studies have documented an increase in the striatal accumulation of [ 18 F]fluorodopa or [ 11 C]dopa in patients with schizophrenia (8)(9)(10)(11)(12). This increased uptake is consistent with increased activity of dopa decarboxylase, an enzyme involved in dopamine synthesis.…”

mentioning

confidence: 94%

Increased baseline occupancy of D ₂ receptors by dopamine in schizophrenia

Abi‐Dargham

Rodenhiser

Printz

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

949

615

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The classical dopamine hypothesis of schizophrenia postulates a hyperactivity of dopaminergic transmission at the D2 receptor. We measured in vivo occupancy of striatal D 2 receptors by dopamine in 18 untreated patients with schizophrenia and 18 matched controls, by comparing D2 receptor availability before and during pharmacologically induced acute dopamine depletion. Acute depletion of intrasynaptic dopamine resulted in a larger increase in D 2 receptor availability in patients with schizophrenia (19% ؎ 11%) compared with control subjects (9% ؎ 7%, P ‫؍‬ 0.003). The increased occupancy of D2 receptors by dopamine occurred both in first-episode neuroleptic-naive patients and in previously treated chronic patients experiencing an episode of illness exacerbation. In addition, elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs. This finding provides direct evidence of increased stimulation of D2 receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons.

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Presynaptic dopaminergic function in the striatum of schizophrenic patients

Cited by 151 publications

References 32 publications

The Dopamine D2 Receptors in High-Affinity State and D3 Receptors in Schizophrenia: A Clinical [11C]-(+)-PHNO PET Study

The Dopamine D2 Receptors in High-Affinity State and D3 Receptors in Schizophrenia: A Clinical [11C]-(+)-PHNO PET Study

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Increased baseline occupancy of D ₂ receptors by dopamine in schizophrenia

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Presynaptic dopaminergic function in the striatum of schizophrenic patients

Cited by 151 publications

References 32 publications

The Dopamine D2 Receptors in High-Affinity State and D3 Receptors in Schizophrenia: A Clinical [11C]-(+)-PHNO PET Study

The Dopamine D2 Receptors in High-Affinity State and D3 Receptors in Schizophrenia: A Clinical [11C]-(+)-PHNO PET Study

Dopamine D2 and D3 binding in people at clinical high risk for schizophrenia, antipsychotic-naive patients and healthy controls while performing a cognitive task

Increased baseline occupancy of D 2 receptors by dopamine in schizophrenia

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Increased baseline occupancy of D ₂ receptors by dopamine in schizophrenia