PET imaging of striatal dopamine D2 receptors in nonhuman primates: Increases in availability produced by chronic raclopride treatment
PET imaging of striatal dopamine D2 receptors in nonhuman primates: Increases in availability produced by chronic raclopride treatment
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DOI：
10.1002/syn.20200
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发表时间：
2005-12-15
期刊：
影响因子：
2.3
通讯作者：
Nader, MA
中科院分区：
文献类型：
--
作者：
Czoty, PW;Gage, HD;Nader, MA
先前使用正电子发射断层扫描（PET）在猴子身上进行的研究表明，获得社会优势可能导致DA D2受体可用性增加，并减弱对可卡因强化作用的敏感性。本研究采用受试者内设计，以确定是否与D2受体拮抗剂雷氯必利长期治疗可以类似地增加D2受体的可用性。使用D2选择性放射性配体[F-18]氟氯必利（FCP），在通过皮下渗透泵给予雷氯必利（0.01 mg/kg/h，持续30 +/-1天）长期治疗前后，对3只成年雄性食蟹猴进行扫描。在治疗期间评估食物强化的操作行为。在雷氯必利治疗的最初8天期间观察到反应的短暂降低。在第十次治疗时出现耐受性，并且在治疗期间和治疗停止后，应答保持在基线水平。平均在猴子，慢性雷氯必利管理增加FCP分布体积比（DVR）之间的12%和20%，在尾状核，壳核，前扣带皮层。当猴子在雷氯必利治疗终止后9-12个月重新扫描时，两名受试者的FCP DVR仍然升高，第三只猴子下降到基线水平以下。考虑到报告的FCP检测/复检变异性为2%，这些结果表明，使用D2受体拮抗剂长期治疗可使PET测量的D2受体可用性大幅增加。观察到恢复率的个体差异，使得DVR的增加在三名受试者中的两名中持续存在。
Previous research using positron emission tomography (PET) in monkeys has shown that attaining social dominance can result in increased DA D2 receptor availability and attenuated sensitivity to the reinforcing effects of cocaine. The present study utilized a within-subjects design to determine whether chronic treatment with the D2 receptor antagonist raclopride could similarly increase D2 receptor availability. Using the D2-selective radioligand [F-18]fluoroclebopride (FCP), three adult male cynomolgus monkeys were scanned before and after chronic treatment with raclopride (0.01 mg/kg per h for 30 +/- 1day) administered by a subcutaneous osmotic pump. Food-reinforced operant behavior was assessed during treatment. A transitory decrease in responding was observed during the initial eight days of raclopride treatment. Tolerance developed by the tenth session, and responding remained at baseline levels for the duration of treatment and after treatment was discontinued. Averaged across monkeys, chronic raclopride administration increased FCP distribution volume ratios (DVRs) between 12 and 20% in the caudate nucleus, putamen, and anterior cingulate cortex. When monkeys were re-scanned 9-12 months after termination of raclopride treatment, FCP DVRs remained elevated in two subjects, and decreased below baseline levels in the third monkey. Considering the reported 2% test/retest variability for FCP, these findings indicate that chronic treatment with a D2 receptor antagonist can produce large increases in D2 receptor availability as measured with PET. Individual differences in rates of recovery were observed, such that the increases in DVR persisted in two of three subjects.