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 D antagonist radiotracers, is the failure to provide information about D receptors configured in a state of high affinity for the agonists (i.e., D receptors coupled to G proteins [D]). The endogenous agonist dopamine binds with preference to D receptors relative to D receptors, making it critical to understand the status of D receptors in SCH.

METHODS

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

RESULTS

A trend-level increase was observed in comparing baseline [C]NPA BP (repeated-measures analysis of variance, F = 3.34, p = .08) between the SCH and HC groups. Amphetamine administration significantly decreased BP in all striatal regions across all subjects in both groups. No differences were observed in [C]NPA ΔBP (repeated-measures analysis of variance, F = 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 [C]NPA BP or ΔBP.

CONCLUSIONS

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