Mu opioid receptor mRNA in nucleus accumbens is elevated following dopamine receptor activation
Mu opioid receptor mRNA in nucleus accumbens is elevated following dopamine receptor activation
复制标题
DOI：
10.1007/bf02532382
复制
发表时间：
1996-11-01
影响因子：
4.4
通讯作者：
Cox, BM
中科院分区：
文献类型：
--
作者：
Azaryan, AV;Clock, BJ;Cox, BM
我们先前已经证明，连续可卡因处理三天可诱导丘脑核中μ阿片受体（莫尔）mRNA的显著但短暂的增加（n. acc.）; SCH 23390和依替氯必利，D1和D2样多巴胺（DA）受体的选择性拮抗剂，分别阻断可卡因诱导的莫尔mRNA的上调。表明DA受体的两个亚家族参与可卡因的作用（1，2）。在本研究中，研究了选择性DA D3受体拮抗剂萘法多曲胺（3，4）阻止可卡因诱导的N. acc.已被检查。此外，还研究了长期给予DA激动剂SKF 38393、R（（+））-6-Bromo-APB氢溴酸盐或溴隐亭后对莫尔mRNA的调节。雄性Sprague-Dawley大鼠用盐水、可卡因、通过渗透微型泵递送的Db受体激动剂或拮抗剂处理3天。莫尔mRNA在n.通过逆转录后的定量竞争性聚合酶链反应（PCR）测定来估计acc.。萘多苷（1.0 mg/kg/天）可防止可卡因诱导的黑猩猩莫尔mRNA上调。单独给药时，萘法多曲胺未改变莫尔mRNA的表达。莫尔mRNA水平在n.用DA激动剂SKF 38393（4.0 mg/kg/天）、R（（+））-6-溴-APB氢溴酸盐（4.0 mg/kg/天）或溴隐亭（5.0 mg/kg/天）处理3天后，因此，DA受体激动剂模拟可卡因对大鼠脑内莫尔mRNA表达的影响。这些数据证实了多巴胺能机制参与可卡因效应的介导，表明间接和直接DA受体激动剂作用的可比性，并指出可卡因作为暴露多巴胺能和阿片系统之间相互作用的工具的有用性。结果提示，莫尔mRNA表达的增加需要多种DA受体的激活。
We have previously demonstrated that continuous cocaine treatment for three days induces a marked but transient increase in mu opioid receptor (MOR) mRNA in nucleus accumbens (n. acc.); SCH 23390 and eticlopride, selective antagonists of D1- and D2-like dopamine (DA) receptors, respectively, blocked this cocaine-induced upregulation of MOR mRNA in n. acc. suggesting involvement of both subfamilies of DA receptors in the effect of cocaine (1,2). In the present study the ability of the selective DA D3 receptor antagonist, nafadotride (3,4), to prevent the cocaine-induced upregulation of MOR mRNA in n. acc. has been examined. Also, regulation of MOR mRNA following chronic administration of the DA agonists, SKF 38393, R((+))-6-Bromo-APB hydrobromide, or bromocriptine, has been studied. Male Sprague-Dawley rats were treated for 3 days with saline, cocaine, the Db receptor agonists or antagonist delivered by osmotic minipump. Expression of MOR mRNA in n. acc. was estimated by quantitative competitive polymerase chain reaction (PCR) assays following reverse transcription. Nafadotride (1.0 mg/kg/day) prevented the cocaine-induced upregulation of MOR mRNA in n. acc. When administered alone, nafadotride did not change the expression of MOR mRNA. The levels of MOR mRNA were elevated in n. acc. after 3 days treatment with each of the DA agonists, SKF 38393 (4.0 mg/kg/day), R((+))-6-Bromo-APB hydrobromide (4.0 mg/kg/day), or bromocriptine (5.0 mg/kg/day). Thus, DA agonists mimick the effect of cocaine on the expression of MOR mRNA in n. acc. These data confirm the involvement of dopaminergic mechanisms in the mediation of cocaine effects, indicate the comparability of actions of indirect and direct DA agonists, and point to the usefulness of cocaine as a tool to expose interaction between dopaminergic and opioid systems. The results suggest that activation of more than one type of DA receptor is required for the increased expression of MOR mRNA.