Effects of the putative dopamine D-3 receptor agonist 7-OH-DPAT in rhesus monkeys trained to discriminate cocaine from saline
Effects of the putative dopamine D-3 receptor agonist 7-OH-DPAT in rhesus monkeys trained to discriminate cocaine from saline
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DOI：
10.1007/bf02247435
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发表时间：
1996-04-01
影响因子：
3.4
通讯作者：
Mello, NK
中科院分区：
文献类型：
--
作者：
Lamas, X;Negus, SS;Mello, NK
这些研究旨在评估假定的多巴胺D-3受体激动剂7-羟基-n， n-二-n-丙基-2-氨基四肽（7-OH-DPAT）单独或与可卡因联合对4只恒河猴的影响，这些恒河猴被训练在固定比例30的食物展示计划下区分可卡因（0.4 mg/kg， IM）和生理盐水。在这些条件下，可卡因的累积剂量（0.013-1.3 mg/kg）对所有猴子的可卡因训练剂量产生剂量依赖性和完全泛化，而对反应率的影响很小。非选择性多巴胺受体拮抗剂氟苯乙醇（0.018 mg/kg， IM）可拮抗可卡因的选择性刺激作用。7-OH-DPAT （0.01 ~ 1.8 mg/kg）对猴子的影响不一致。在4只猴子中的两只（L990和L958）中，7-OH-DPAT持续且完全地对可卡因起作用，并以剂量依赖的方式降低了反应率。氟苯酚可拮抗7-OH-DPAT的可卡因样判别刺激作用和降速作用。低剂量7-OH-DPAT预处理（0.01 ~ 0.032 mg/kg）对猴L990和L958的可卡因剂量效应曲线无影响；然而，较高剂量的7-OH-DPAT （0.032-0.32 mg/kg）使可卡因剂量效应曲线向左移动。在另外两只猴子（猴子150F和猴子89B036）中，7-OH-DPAT产生了剂量依赖性的反应率下降，但并没有一致地推广到可卡因。氟哌辛醇对7-OH-DPAT的降速作用无拮抗作用，7-OH-DPAT预处理（0.1 ~ 0.32 mg/kg）可降低反应率，但对可卡因剂量效应曲线无影响。时间过程实验显示，0.32 mg/kg的7-OH-DPAT比训练剂量的可卡因起效更慢，作用持续时间更长。最后，D-3/D-2多巴胺激动剂喹匹罗在3只猴子中完全转化为可卡因，在第4只猴子中部分转化为可卡因。喹匹罗在那些7-OH-DPAT持续作用于可卡因的猴子身上显示出最高的效力。本研究结果表明，在恒河猴中，7-OH-DPAT产生类似可卡因的作用，并可能调节某些猴子对可卡因的鉴别刺激作用。
These studies were designed to evaluate the effects of the putative dopamine D-3 receptor agonist 7-hydroxy-N,N-di-n-propyl-2-aminotetraline (7-OH-DPAT), alone and in combination with cocaine, in four rhesus monkeys trained to discriminate cocaine (0.4 mg/kg, IM) from saline under a fixed-ratio 30 schedule of food presentation. Under these conditions, cumulative doses of cocaine (0.013-1.3 mg/kg) produced a dose-dependent and complete generalization to the training dose of cocaine in all monkeys, while producing only minimal effects on response rates. The discriminative stimulus effects of cocaine were antagonized by the non-selective dopamine receptor antagonist flupenthixol (0.018 mg/kg, IM) in all four monkeys. The effects of 7-OH-DPAT (0.01-1.8 mg/kg) were inconsistent across monkeys. In two of the four monkeys (monkeys L990 and L958), 7-OH-DPAT consistently and completely generalized to cocaine and decreased response rates in a dose-dependent manner. Both the cocaine-like discriminative stimulus effects and rate-decreasing effects of 7-OH-DPAT were antagonized by flupenthixol in these two monkeys. Pretreatment with low doses of 7-OH-DPAT (0.01-0.032 mg/kg) had no effect on the cocaine dose-effect curve in monkeys L990 and L958; however, higher doses of 7-OH-DPAT (0.032-0.32 mg/kg) shifted the cocaine dose-effect curve to the left. In the other two monkeys (monkeys 150F and 89B036), 7-OH-DPAT produced a dose-dependent decrease in response rates but did not consistently generalize to cocaine. Flupenthixol did not antagonize the rate-decreasing effects of 7-OH-DPAT in these two monkeys, and pretreatment with 7-OH-DPAT (0.1-0.32 mg/kg) produced a decrease in response rates but had no effect on the cocaine dose-effect curve. Time-course experiments revealed that 7-OH-DPAT (0.32 mg/kg) displayed a slower onset and a longer duration of effect than the training dose of cocaine. Finally, the D-3/D-2 dopamine agonist quinpirole completely generalized to cocaine in three monkeys, and partially in the fourth monkey. Quinpirole showed the highest potency in those monkeys in which 7-OH-DPAT consistently generalized to cocaine. The results of the present study suggest that, in rhesus monkeys, 7-OH-DPAT produces cocaine-like effects and may modulate the discriminative stimulus effects of cocaine in some monkeys.