Amphetamine-Induced Striatal Dopamine Release Measured With an Agonist Radiotracer in Schizophrenia.
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.
['Frankle|W Gordon|WG|', 'Paris|Jennifer|J|', 'Himes|Michael|M|', 'Mason|N Scott|NS|', 'Mathis|Chester A|CA|', 'Narendran|Rajesh|R|']
D000293:Adolescent D000328:Adult D000661:Amphetamine D001058:Apomorphine D003342:Corpus Striatum D004298:Dopamine D018491:Dopamine Agonists D018765:Dopamine Uptake Inhibitors D005260:Female D006801:Humans D008297:Male D049268:Positron-Emission Tomography D011849:Radioactive Tracers D012559:Schizophrenia D055815:Young Adult
Dopamine Schizophrenia High affinity Amphetamine Positron emission tomography (PET) [(11)C]N-propyl-norapomorphine (NPA)