Involvement of dopamine uptake in the discriminative stimulus effects of cocaine1,2
Involvement of dopamine uptake in the discriminative stimulus effects of cocaine1,2
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多巴胺摄取参与可卡因的辨别刺激效应1,2
DOI：
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发表时间：
1991
影响因子：
1.6
通讯作者：
J. B. Appel
中科院分区：
文献类型：
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作者：
J. Broadbent;E. K. Michael;E. Riddle;J. B. Appel
多巴胺能和肾上腺素能机制参与可卡因的刺激作用进行了研究，在大鼠训练区分可卡因从盐水。可卡因（10 mg/kg）的线索一般化为主要通过抑制DA摄取起作用的化合物，其效力顺序为诺米芬辛（ED 50，= 0.38 mg/kg）> GBR 12909（1-{2-[双（4-氟苯基）甲氧基]-乙基]}-4-甲氧基苯基）-1H-吡唑（3-苯丙基）哌嗪（ED 50 = 4.38 mg/kg）>安非他酮（ED 50 = 11.6 mg/kg），但不适用于：（1）直接激活突触后DA受体（溴隐亭），（2）释放DA（金刚烷胺），（3）对突触前DA受体具有拮抗作用（顺式氟噻吨），或（4）抑制NE的摄取（地昔帕明、丙咪嗪、尼索西汀）。当与可卡因联合使用时，D2受体拮抗剂（-）舒必利对可卡因杠杆选择没有显著影响。这些结果表明，DA摄取的抑制涉及可卡因的区别性刺激特性，因为（1）通过抑制DA摄取而不是通过一些其他机制模拟可卡因起作用的化合物，以及（2）这些药物对DA转运位点的亲和力和它们在阻断可卡因中的效力顺序是相同的。
The involvement of dopaminergic and adrenergic mechanisms in the stimulus effects of cocaine was studied in rats trained to discriminate cocaine from saline. The cocaine (10 mg/kg) cue generalized to compounds that act primarily by inhibiting DA uptake with an order of potency of nomifensine (ED50, = 0.38 mg/kg) > GBR12909 (l-{2-[bis(4-fluorophenyl) methoxy]-ethyl]}-4(3-phenylpropyl) piperazine (ED50 = 4.38 mg/kg) > bupropion (ED50 = 11.6 mg/kg) but not to those that: (1) directly activate postsynaptic DA receptors (bromocriptine), (2) release DA (amantadine), (3) have antagonist actions at presynaptic DA receptors (cis-flupenthixol) or, (4) inhibit the uptake of NE (desipramine, imipramine, nisoxetine). When given in combination with cocaine, the D2 receptor antagonist (-)sulpiride had no significant effects on cocaine-lever selection. These results suggest that inhibition of DA uptake is involved in the discriminative stimulus properties of cocaine since, (1) compounds that act by inhibiting DA uptake rather than through some other mechanism mimic cocaine and, (2) the reported affinities of these drugs for the DA transport site and their order of potency in blocking cocaine are identical.