Czoty Paul W, Gage H Donald, Garg Pradeep K, Garg Sudha, Nader Michael A
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, NC, 27157-1083, USA.
Psychopharmacology (Berl). 2013 Sep 29. doi: 10.1007/s00213-013-3274-7.
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 4 days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [F]fluoroclebopride (FCP). Four additional monkeys were studied using [C]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.
多巴胺（DA）受体激动剂和拮抗剂的长期治疗可对DA D2/D3受体数量和功能的测量指标产生不同影响，但D2/D3受体部分激动剂的长期治疗效果尚不清楚。
我们在雄性食蟹猴中采用受试者内设计，以确定D2/D3受体部分激动剂阿立哌唑（ARI；0.03mg/kg和0.1mg/kg，肌肉注射）重复（17天）治疗对食物强化行为（n = 5）以及用正电子发射断层扫描（PET；n = 9）测量的D2/D3受体可用性的影响。
五只猴子在固定比例为50的食物强化计划下做出反应，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[F]氟哌利多（FCP）测量D2/D3受体可用性。另外四只猴子使用[C]雷氯必利进行研究，并依次用每种剂量的ARI治疗17天。
ARI减少了由食物维持的反应，耐受性证据最少。在大多数猴子中，重复给予ARI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最高的猴子中观察到减少。
结果表明，用低效DA受体部分激动剂重复治疗对脑D2/D3受体可用性产生的影响在性质上不同于高效受体激动剂和拮抗剂，并表明观察到的对ARI治疗反应的个体差异可能反映了其部分激动剂活性。
