Book contents
- Frontmatter
- Contents
- Foreword
- Acknowledgments
- Introduction
- 1 The life history of dopamine
- 2 Enzymology of tyrosine hydroxylase
- 3 The assay of tyrosine hydroxylase
- 4 Enzymology of aromatic amino acid decarboxylase
- 5 PET studies of DOPA utilization
- 6 Conjugation and sulfonation of dopamine and its metabolites
- 7 Dopamine synthesis and metabolism rates
- 8 MAO activity in the brain
- 9 Vesicular storage of dopamine
- 10 Dopamine release: from vesicles to behavior
- 11 The plasma membrane dopamine transporter
- 12 Dopamine receptors
- 13 Imaging dopamine D1 receptors
- 14 Imaging dopamine D2 receptors
- 15 Factors influencing D2 binding in living brain
- 16 The absolute abundance of dopamine receptors in the brain
- 17 Conclusions and perspectives
- References
- Index
- Plate section
15 - Factors influencing D2 binding in living brain
Published online by Cambridge University Press: 04 December 2009
- Frontmatter
- Contents
- Foreword
- Acknowledgments
- Introduction
- 1 The life history of dopamine
- 2 Enzymology of tyrosine hydroxylase
- 3 The assay of tyrosine hydroxylase
- 4 Enzymology of aromatic amino acid decarboxylase
- 5 PET studies of DOPA utilization
- 6 Conjugation and sulfonation of dopamine and its metabolites
- 7 Dopamine synthesis and metabolism rates
- 8 MAO activity in the brain
- 9 Vesicular storage of dopamine
- 10 Dopamine release: from vesicles to behavior
- 11 The plasma membrane dopamine transporter
- 12 Dopamine receptors
- 13 Imaging dopamine D1 receptors
- 14 Imaging dopamine D2 receptors
- 15 Factors influencing D2 binding in living brain
- 16 The absolute abundance of dopamine receptors in the brain
- 17 Conclusions and perspectives
- References
- Index
- Plate section
Summary
Pharmacological modulation
Dopamine antagonists
Just as the abundance of striatal dopamine D2 receptors increases after prolonged dopamine depletion, chronic pharmacological blockade can also result in receptor upregulation. For example, chronic neuroleptic treatment increased dopamine D2/3 receptor binding site density in rat striatum by 19%, whereas the specific binding to D4 receptors increased two-fold (Schoots et al. 1995). In another study, chronic haloperidol treatment increased [3H]spiperone binding (in the presence of a 5HT2 antagonist) in rat striatum membranes by 40%, but the antipsychotic treatment was without effect on the apparent fraction of those receptors which could be displaced by agonists, i.e. D2High (MacKenzie & Zigmond 1984). Similar increases in D2 antagonist binding have also been seen in the striatum of monkeys after prolonged pharmacological blockade with receptor antagonists (Huang et al. 1997).
Pharmacologically evoked changes in dopamine receptor availability can be extremely long-lasting. In a primate PET study, daily treatment with raclopride (10 μg k g− 1 × 30 days) increased the striatal binding of the D2-selective antagonist [18F]fluoroclebopride by 12–20%, an increase which persisted for 1 year in two of the three monkeys investigated (Czoty, Gage, & Nader 2005). In a case report of two patients with schizophrenia who had undergone treatment with haloperidol for many years, a non-smoker had a 98% increase in [11C]raclopride pB and suffered from tardive dyskinesia, whereas a smoker, treated at a much higher haloperidol dose, had somewhat lower elevation in pB, and no tardive symptoms (Silvestri et al. 2004).
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- Information
- Imaging Dopamine , pp. 203 - 223Publisher: Cambridge University PressPrint publication year: 2009