Amphetamine-Induced Striatal Dopamine Release Measured With an Agonist Radiotracer in Schizophrenia.

Abstract

BACKGROUND:

Receptor imaging studies have reported increased amphetamine-induced dopamine release in subjects with schizophrenia (SCH) relative to healthy control subjects (HCs). A limitation of these studies, performed with D2/3 antagonist radiotracers, is the failure to provide information about D2/3 receptors configured in a state of high affinity for the agonists (i.e., D2/3 receptors coupled to G proteins [D2/3 HIGH]). The endogenous agonist dopamine binds with preference to D2/3 HIGH receptors relative to D2/3 LOW receptors, making it critical to understand the status of D2/3 HIGH receptors in SCH.

METHODS:

D2/3 agonist positron emission tomography radiotracer [11C]N-propyl-norapomorphine ([11C]NPA) binding potential (BPND) was measured in 14 off-medication subjects with SCH and 14 matched HCs at baseline and after the administration of 0.5 mg kg-1 oral D-amphetamine. The amphetamine-induced change in BPND (ΔBPND) was calculated as the difference between BPND in the postamphetamine condition and BPND in the baseline condition and was expressed as a percentage of BPND at baseline.

RESULTS:

A trend-level increase was observed in comparing baseline [11C]NPA BPND (repeated-measures analysis of variance, F1,26 = 3.34, p = .08) between the SCH and HC groups. Amphetamine administration significantly decreased BPND in all striatal regions across all subjects in both groups. No differences were observed in [11C]NPA ΔBPND (repeated-measures analysis of variance, F1,26 = 1.9, p = .18) between HCs and subjects with SCH. Amphetamine significantly increased positive symptoms in subjects with SCH (19.5 ± 5.3 vs. 23.7 ± 4.1, paired t test, p < .0001); however, no correlations were noted with [11C]NPA BPND or ΔBPND.

CONCLUSIONS:

This study provides in vivo indication of a role for postsynaptic factors in amphetamine-induced psychosis in SCH.

• Authors: W Gordon Frankle, Jennifer Paris, Michael Himes, N Scott Mason, Chester A Mathis, Rajesh Narendran
• Journal: Biological psychiatry (Biol Psychiatry) Vol. 83 Issue 8 Pg. 707-714 (04 15 2018) ISSN: 1873-2402 [Electronic] United States
• PMID: 29325847 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2017 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Chemical References

• Dopamine Agonists
• Dopamine Uptake Inhibitors
• Radioactive Tracers
• N-n-propylnorapomorphine
• Amphetamine
• Apomorphine
• Dopamine

Topics

• Adolescent
• Adult
• Amphetamine (pharmacology)
• Apomorphine (analogs & derivatives, pharmacokinetics)
• Corpus Striatum (diagnostic imaging, drug effects)
• Dopamine (metabolism)
• Dopamine Agonists (pharmacokinetics)
• Dopamine Uptake Inhibitors (pharmacology)
• Female
• Humans
• Male
• Positron-Emission Tomography (methods)
• Radioactive Tracers
• Schizophrenia (diagnostic imaging, metabolism)
• Young Adult