Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats
Dopamine D1 and D3 receptor interactions in cocaine reward and seeking in rats
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DOI：
10.1007/s00213-016-4420-9
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发表时间：
2016-12-01
影响因子：
3.4
通讯作者：
Ranaldi, R.
中科院分区：
文献类型：
--
作者：
Galaj, E.;Harding, W.;Ranaldi, R.
动物研究已证明多巴胺 D1 和 D3 受体在可卡因奖励和寻求中的作用。在这里，我们研究了这两种多巴胺受体在提示诱导恢复可卡因寻求、可卡因条件性位置偏爱 (CPP) 和可卡因自我给药方面的潜在相互作用。D3 受体拮抗剂 NGB 2904 和 D1 部分激动剂 SKF 77434 的共同给药，在恢复或 CPP 测试之前，单独服用不会产生显着效果的剂量显着减少了杠杆按压和在可卡因配对环境中花费的时间，这表明组合化合物对可卡因寻求具有协同作用。当大鼠按照 NGB 2904 强化剂量渐进比例方案自我施用可卡因时，单独使用无效，显着增强了 SKF 77434 的断点减少效果。我们的结果表明，D1 受体部分激动剂和 D3 受体拮抗剂的联合治疗可显着降低可卡因寻求和奖励。这表明多巴胺 D1 和 D3 受体在可卡因相关行为中存在相互作用。
Animal research has demonstrated a role of dopamine D1 and D3 receptors in cocaine reward and seeking.Here, we investigated the potential interaction of these two dopamine receptors in cue-induced reinstatement of cocaine seeking, cocaine conditioned place preference (CPP), and cocaine self-administration in rats.The co-administration of a D3 receptor antagonist, NGB 2904 and a D1 partial agonist, SKF 77434, of doses which when administered individually produced no significant effects, prior to reinstatement or CPP tests significantly reduced lever pressing and time spent in the cocaine-paired environment, suggesting synergistic effects of the combined compounds on cocaine seeking. When given to rats self-administering cocaine under a progressive ratio schedule of reinforcement doses of NGB 2904 which were ineffective alone significantly enhanced the break point-reducing effects of SKF 77434.Our results indicate that the combined treatment with a D1 receptor partial agonist and D3 receptor antagonist produces robust decreases in cocaine seeking and reward. This suggests an interaction between dopamine D1 and D3 receptors in cocaine-related behaviors.