PARTIAL AND FULL DOPAMINE D1-RECEPTOR AGONISTS IN MICE AND RATS - RELATION BETWEEN BEHAVIORAL-EFFECTS AND STIMULATION OF ADENYLATE-CYCLASE ACTIVITY INVITRO
PARTIAL AND FULL DOPAMINE D1-RECEPTOR AGONISTS IN MICE AND RATS - RELATION BETWEEN BEHAVIORAL-EFFECTS AND STIMULATION OF ADENYLATE-CYCLASE ACTIVITY INVITRO
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DOI：
10.1016/0014-2999(92)90690-6
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发表时间：
1992-03-24
影响因子：
5
通讯作者：
SANCHEZ, C
中科院分区：
文献类型：
--
作者：
ARNT, J;HYTTEL, J;SANCHEZ, C
多巴胺（DA）D1激动剂，SK&F 83959，SK&F 75670，SK&F 38993，SK&F 81297和SK&F 80723，有不同的能力，刺激大鼠纹状体匀浆腺苷酸环化酶活性。与100 μ M DA的作用相比，它们的效力分别为0、33、69、68和81%。在大鼠中，所有化合物均诱导（1）单侧6-羟基-DA损伤后的对侧盘旋行为，（2）与D2激动剂喹吡罗共同治疗后中脑半横断后的同侧盘旋行为，以及（3）与喹吡罗组合后的口腔刻板行为。在三种试验模型中，最大效应和效力的等级顺序相似。在小鼠SK&F 83959中，SK&F 75670和SK&F 38393抑制哌甲酯诱导的啃咬行为，并且不诱导或仅诱导弱的运动过度。SK&F 81297诱导明显的运动过度，其被SK&F 83959和SK&F 75670部分抑制，并且被D1拮抗剂SCH 23390完全阻断。可以得出结论，没有关系可以证明之间的效力，以刺激腺苷酸环化酶和诱导大鼠的盘旋行为和刻板印象。相反，在小鼠模型中发现了生物化学和行为功效之间的关系。结果表明，不同亚型的D1受体介导的行为的影响，在这项研究中报告。
The dopamine (DA) D1 agonists, SK&F 83959, SK&F 75670, SK&F 38993, SK&F 81297 and SK&F 80723, had variable abilities to stimulate adenylate cyclase activity in rat striatal homogenates. Their efficacies, in relation to the effect of 100-mu-M DA were 0, 33, 69, 68 and 81%, respectively. In rats, all compounds induced (1) contralateral circling behaviour after unilateral 6-hydroxy-DA lesions, (2) ipsilateral circling behaviour after midbrain hemitransection after cotreatment with the D2 agonist quinpirole and (3) oral stereotypies after their combination with quinpirole. Maximum effects and rank order of potencies were similar in the three test models. In mice SK&F 83959, SK&F 75670 and SK&F 38393 inhibited methylphenidate-induced gnawing behaviour and induced no or only weak hypermotility. SK&F 81297 induced marked hypermotility which was partially inhibited by SK&F 83959 and SK&F 75670 and was completely blocked by the D1 antagonist, SCH 23390. It is concluded that no relation could be demonstrated between the efficacy to stimulate adenylate cyclase and to induce circling behaviours and stereotypies in rats. In contrast, a relation between biochemical and behavioural efficacies was found in the mouse models. The results suggest that different subtypes of D1 receptors mediate the behavioural effects reported in this study.