Baseline and Amphetamine-Stimulated Dopamine Activity Are Related in Drug-Naïve Schizophrenic Subjects

  title={Baseline and Amphetamine-Stimulated Dopamine Activity Are Related in Drug-Na{\"i}ve Schizophrenic Subjects},
  author={Anissa Abi-Dargham and Elsmarieke van de Giessen and Mark Slifstein and Lawrence S. Kegeles and Marc Laruelle},
  journal={Biological Psychiatry},

Striatal dopamine D2/3 receptors in medication-naïve schizophrenia: an [123I] IBZM SPECT study.

Medication-naïve patients with recent-onset schizophrenia have similar D2/3 receptor availability to healthy controls and future treatments should target the presynaptic control of dopamine synthesis and release, according to SPECT results.

Discordant behavioral effects of psychotomimetic drugs in mice with altered NMDA receptor function

The results of the PCP experiments demonstrate that convergence of pharmacological and genetic manipulations at NMDARs may confound the predictive validity of these preclinical assays for the effects of GMS activation in schizophrenia, and provide additional evidence that hyperdopaminergia in schizophrenia may be distinct from N MDAR hypofunction.

Role of GABA Deficit in Sensitivity to the Psychotomimetic Effects of Amphetamine

GA deficits increased vulnerability to amphetamine-induced psychosis-relevant effects in healthy subjects, suggesting that pre-existing GABA deficits may explain why a subgroup of schizophrenia patients are vulnerable to AMPH.

Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder

Striatal dopamine D2/3 receptor binding following dopamine depletion in subjects at Ultra High Risk for psychosis

PET imaging of dopamine-D2 receptor internalization in schizophrenia

Results show similar pattern of return of BPND to baseline as a function of time in patients with SZ and HC, suggesting that striatal D2R internalization as measured by the imaging paradigm is normal in patientsWith SZ.

Presynaptic Dopamine in Schizophrenia

Overall, these different imaging modalities have converged to show a dysregulation of presynaptic dopaminergic activity in schizophrenia, leading to excessive DA release in the striatum, particularly in the projection to the associativestriatum, an area of integration between cognitive and limbic cortical inputs.

The amphetamine sensitization model of schizophrenia symptoms and its effect on schedule-induced polydipsia in the rat

Findings suggest that hyperdopaminergia associated with schizophrenia may contribute to the development of polydipsia in this population of at-risk individuals.



Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects.

In the schizophrenic group, elevated amphetamine effect on [123I]IBZM binding potential was associated with emergence or worsening of positive psychotic symptoms, suggesting that psychotic symptoms elicited in this experimental setting in schizophrenia patients are associated with exaggerated stimulation of dopaminergic transmission.

Increased baseline occupancy of D2 receptors by dopamine in schizophrenia.

Elevated synaptic dopamine was predictive of good treatment response of positive symptoms to antipsychotic drugs and increased stimulation of D(2) receptors by dopamine in schizophrenia, consistent with increased phasic activity of dopaminergic neurons.

Increased striatal dopamine transmission in schizophrenia: confirmation in a second cohort.

In this new cohort of subjects the authors replicated their initial observation of a dysregulation of striatal dopamine release in schizophrenia, with a significantly larger reduction in D2 receptor availability following acute amphetamine challenge than the comparison group.

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

  • A. BreierT. Su D. Pickar
  • Biology, Psychology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1997
In the clinical study, patients with schizophrenia compared with healthy volunteers had significantly greater amphetamine-related reductions in [11C]raclopride specific binding, providing direct evidence for the hypothesis of elevated Amphetamine-induced synaptic dopamine concentrations in schizophrenia.

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

The results do not find support for the hypothesis linking psychosis to a selective increase in D2high and/or D3 in schizophrenia, and it is possible that receptors with high affinity are not accessible by [11C]-(+)-PHNO because they are occupied by endogenous dopamine.