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Biol Psychiatry. 2018 Apr 15;83(8):707-714. doi: 10.1016/j.biopsych.2017.11.032. Epub 2017 Dec 7.

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

Author information

1
Department of Psychiatry, NYU Langone Medical Center, New York, New York. Electronic address: william.frankle@nyumc.org.
2
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania.
3
Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.
4
Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania; Department of Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania.

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.

KEYWORDS:

Amphetamine; Dopamine; High affinity; Positron emission tomography (PET); Schizophrenia; [(11)C]N-propyl-norapomorphine (NPA)

PMID:
29325847
PMCID:
PMC5862747
[Available on 2019-04-15]
DOI:
10.1016/j.biopsych.2017.11.032

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