Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys.
Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys.
复制标题
多巴胺D2/D3受体部分激动剂阿立哌唑的反复治疗对猴子纹状体D2/D3受体的可用性的影响。
DOI：
10.1007/s00213-013-3274-7
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发表时间：
2013-09-29
影响因子：
3.4
通讯作者：
Nader, Michael A.
中科院分区：
文献类型：
--
作者：
Czoty, Paul W.;Gage, H. Donald;Garg, Pradeep K.;Garg, Sudha;Nader, Michael A.
多巴胺（DA）受体激动剂和拮抗剂的长期治疗可以不同地影响DA D2/D3受体的数量和功能的措施，但与部分D2/D3受体激动剂的长期治疗的效果尚不清楚。我们在雄性食蟹猴中使用受试者内设计，以确定D2/D3受体部分激动剂阿立哌唑（ARI; 0.03 mg/kg和0.1 mg/kg i.m.）食物强化行为（n=5）和D2/D3受体的可用性，用正电子发射断层扫描（PET; n=9）测量。5只猴子在固定比例50的食物强化方案下做出反应，并在ARI治疗前和治疗后4天使用PET和D2/D3受体选择性放射性配体[18F]氟氯必利（FCP）测量D2/D3受体可用性。使用[11 C]雷氯必利对另外4只猴子进行了研究，并连续使用每种剂量的ARI治疗17天。ARI降低了食物维持反应，耐受性证据最少。在大多数猴中，重复ARI给药增加了尾状核和壳核中的FCP和雷氯必利分布体积比（DVR），但在基线DVR最高的猴中观察到了减少。结果表明，重复治疗与低效率DA受体部分激动剂产生的影响，脑D2/D3受体的可用性，是定性的高效率受体激动剂和拮抗剂的不同，并建议，观察到的个体差异响应ARI治疗可能反映其部分激动剂活性。
Chronic treatment with dopamine (DA) receptor agonists and antagonists can differentially affect measures of DA D2/D3 receptor number and function, but the effects of chronic treatment with a partial D2/D3 receptor agonist are not clear. We used a within-subjects design in male cynomolgus monkeys to determine the effects of repeated (17-day) treatment with the D2/D3 receptor partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food-reinforced behavior (n=5) and on D2/D3 receptor availability as measured with positron emission tomography (PET; n=9). Five monkeys responded under a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability was measured before and four days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional monkeys were studied using [11C]raclopride and treated sequentially with each dose of ARI for 17 days. ARI decreased food-maintained responding with minimal evidence of tolerance. Repeated ARI administration increased FCP and raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen in most monkeys, but decreases were observed in monkeys with the highest baseline DVRs. The results indicate that repeated treatment with a low efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor availability that are qualitatively different from those of both high-efficacy receptor agonists and antagonists, and suggest that the observed individual differences in response to ARI treatment may reflect its partial agonist activity.
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影响因子：
3.3
作者：
KLAWANS, HL;RUBOVITS, R
通讯作者：
RUBOVITS, R
DOI：
10.1023/a:1015276028425
发表时间：
2002-03-01
期刊：
Annals of clinical psychiatry : official journal of the American Academy of Clinical Psychiatrists
影响因子：
--
作者：
Gerlach, Jes
通讯作者：
Gerlach, Jes
影响因子：
2.3
作者：
Czoty, PW;Gage, HD;Nader, MA
通讯作者：
Nader, MA
影响因子：
6.3
作者：
LOGAN, J;FOWLER, JS;CHRISTMAN, DR
通讯作者：
CHRISTMAN, DR
影响因子：
7.6
作者：
Lile, JA;Stoops, WW;Rush, CR
通讯作者：
Rush, CR