Ginovart N, Farde L, Halldin C, Swahn C G
Karolinska Institutet, Department of Clinical Neuroscience, Karolinska Hospital, Stockholm, Sweden.
Synapse. 1999 Feb;31(2):154-62. doi: 10.1002/(SICI)1098-2396(199902)31:2<154::AID-SYN9>3.0.CO;2-K.
Recent brain imaging studies suggest that schizophrenia may be related to abnormally high amphetamine-induced dopamine release. It is known that repeated use of amphetamine may cause paranoid psychosis and persisting stereotypies. The biochemical background for these signs and symptoms has not been clarified. In this study, positron emission tomography and [11C]raclopride were used to determine central D2-dopamine receptor density (Bmax) and apparent affinity (K(D)app) in Cynomolgus monkeys before and after 14 days of treatment with d-amphetamine sulphate (2 mg/kg/day; s.c.). One day after withdrawal from amphetamine, K(D)app was increased, suggesting [11C]raclopride competition with elevated concentration of dopamine. At 7 and 14 days after withdrawal, there was a 19-26% decrease in Bmax but no change in K(D)app as compared to baseline. Although this study was performed on two monkeys only, there was thus no support for the view that chronic intermittent hyperactivity of the dopamine system may be related to an upregulation of striatal D2-dopamine receptors. Repeated administration of amphetamine may, rather, cause a long-lasting downregulation of the D2-receptor density, which may be a neurochemical correlate to the abnormal movements, anhedonia, anxiety, and depression seen in psychostimulant abusers.
近期的脑成像研究表明，精神分裂症可能与苯丙胺诱导的多巴胺释放异常增高有关。已知反复使用苯丙胺可能导致偏执性精神病和持续性刻板行为。这些症状和体征的生化背景尚未阐明。在本研究中，使用正电子发射断层扫描和[11C]雷氯必利来测定食蟹猴在硫酸右苯丙胺（2mg/kg/天；皮下注射）治疗14天前后的中枢D2-多巴胺受体密度（Bmax）和表观亲和力（K(D)app）。停用苯丙胺一天后，K(D)app升高，提示[11C]雷氯必利与升高的多巴胺浓度存在竞争。在停药后7天和14天，与基线相比，Bmax下降了19%-26%，但K(D)app没有变化。尽管本研究仅在两只猴子身上进行，但因此没有证据支持多巴胺系统慢性间歇性多动可能与纹状体D2-多巴胺受体上调有关的观点。相反，反复给予苯丙胺可能导致D2受体密度的长期下调，这可能是精神兴奋剂滥用者出现异常运动、快感缺失、焦虑和抑郁的神经化学相关因素。
