Effects of the 5HT2C antagonist SB242084 on the pramipexole-induced potentiation of water contrafreeloading, a putative animal model of compulsive behavior
Effects of the 5HT2C antagonist SB242084 on the pramipexole-induced potentiation of water contrafreeloading, a putative animal model of compulsive behavior
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DOI：
10.1007/s00213-012-2938-z
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发表时间：
2013-05-01
影响因子：
3.4
通讯作者：
Nencini, Paolo
中科院分区：
文献类型：
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作者：
Schepisi, Chiara;De Carolis, Lorenza;Nencini, Paolo
在大鼠中，多巴胺D2/D3受体激动剂喹吡罗（quinpirole）可同时诱发过度饮水和水“逆向负荷”（CFL），这是一种假定的强迫性模型。D3受体在这种效应中的作用尚不清楚。氯丙咪嗪（CIM）被发现对比过度口渴和CFL，但5-羟色胺在这种效果中的作用需要进一步investment.We研究了优先D3激动剂普拉克索（PPX）在这两种模型中的影响。此外，我们还检测了PPX诱导的CFL对CIM和5-HT 2c拮抗剂SB 242084的敏感性。实验1中，每天腹腔注射PPX（0 ~ 1.0 mg/kg）8次后，在2 h和5 h测量饮水量。在CFL研究中，每隔三分之一杠杆按压，大鼠通过水的输送得到加强。在第1-6天，仅在压杆时才可获得水。在第7至15天，提供了应急特遣队和自由出入之间的选择。给予如实验1中的PPX剂量。在另外两个实验中，单独施用PPX（0.5mg/kg）或与CIM（5或10 mg/kg）或SB 242084（0.3或1.0mg/kg）组合施用PPX（0.5mg/kg）JPX不产生过度饮水，但增强自发CFL。SB 242084比CIM更有效地减弱PPX诱导的CFL，恢复对自由获取水的偏好。CFL，但不是烦渴，是由优先D3激活诱导的，这种作用被5 HT 2c受体阻断剂阻止。由于PPX干扰决策和5-HT 2c受体超敏性参与了强迫行为的表达，本研究支持多巴胺能诱导的CFL的强迫性质。
In rats, quinpirole, a dopaminergic D2/D3 receptor agonist, elicits both hyperdipsia and water "contrafreeloading" (CFL), a putative model of compulsivity. The role of D3 receptors in this effect remains unclear. Clomipramine (CIM) was found to contrast both hyperdipsia and CFL, but the role of serotonin in this effect requires further investigation.We studied the effects of the preferential D3 agonist pramipexole (PPX) in both models. Furthermore, we tested the sensitivity of PPX-induced CFL to CIM and to the 5HT2c antagonist SB242084.In experiment 1, drinking was measured at 2 and 5 h after eight daily injections of PPX (0 to 1.0 mg/kg intraperitoneally). In the CFL study, every other third lever press, the rat was reinforced by the delivery of water. On days 1-6, water was only available upon lever pressing. On days 7-15, choice between response-contingent and free access was provided. PPX doses as in the experiment 1 were given. In two further experiments, PPX (0.5 mg/kg) was administered alone or in combination with CIM (5 or 10 mg/kg) or SB242084 (0.3 or 1.0 mg/kg).PPX did not produce hyperdipsia but enhanced spontaneous CFL. SB242084 attenuated PPX-induced CFL more effectively than CIM, restoring the preference for free access to water.CFL, but not polydipsia, was induced by preferential D3 activation, an effect prevented by 5HT2c receptor blockade. Since PPX interferes with decision making and 5HT2c receptor supersensitivity is involved in the expression of compulsive behaviors, this study supports the compulsive nature of dopaminergic-induced CFL.