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.

中文翻译：

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用激动剂放射性示踪剂在精神分裂症中测量苯丙胺诱导的纹状体多巴胺释放

背景 受体成像研究报告了精神分裂症 (SCH) 受试者相对于健康对照受试者 (HC) 的苯丙胺诱导的多巴胺释放增加。这些使用 D2/3 拮抗剂放射性示踪剂进行的研究的局限性在于未能提供有关 D2/3 受体的信息，这些受体配置为对激动剂具有高亲和力（即与 G 蛋白偶联的 D2/3 受体 [D2/3高的]）。相对于 D2/3 LOW 受体，内源性激动剂多巴胺优先结合 D2/3 HIGH 受体，因此了解 SCH 中 D2/3 HIGH 受体的状态至关重要。方法 D2/3 激动剂正电子发射断层扫描放射性示踪剂 [11C]N-丙基-去甲吗啡 ([11C]NPA) 结合电位 (BPND) 在 14 名患有 SCH 和 14 名匹配 HCs 的停药受试者中测量. 5 mg kg-1 口服 D-苯丙胺。苯丙胺诱导的 BPND 变化 (ΔBPND) 计算为苯丙胺后条件下的 BPND 与基线条件下的 BPND 之间的差异，并表示为基线时 BPND 的百分比。结果 在比较 SCH 和 HC 组之间的基线 [11C]NPA BPND（重复测量方差分析，F1,26 = 3.34，p = .08）时，观察到趋势水平增加。苯丙胺给药显着降低了两组所有受试者所有纹状体区域的 BPND。[11C]NPA ΔBPND（重复测量方差分析，F1,26 = 1.9，p = .18）在 HC 和 SCH 受试者之间没有观察到差异。苯丙胺显着增加了 SCH 受试者的阳性症状（19.5 ± 5.3 对 23.7 ± 4.1，配对 t 检验，p < .0001）；然而，[11C]NPA BPND 或 ΔBPND 没有发现相关性。结论 本研究提供了突触后因子在苯丙胺诱导的 SCH 精神病中的作用的体内指示。