EVIDENCE THAT THE AVERSIVE EFFECTS OF OPIOID ANTAGONISTS AND KAPPA-AGONISTS ARE CENTRALLY MEDIATED
EVIDENCE THAT THE AVERSIVE EFFECTS OF OPIOID ANTAGONISTS AND KAPPA-AGONISTS ARE CENTRALLY MEDIATED
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DOI：
10.1007/bf00444692
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发表时间：
1989-01-01
影响因子：
3.4
通讯作者：
SHIPPENBERG, TS
中科院分区：
文献类型：
--
作者：
BALSKUBIK, R;HERZ, A;SHIPPENBERG, TS
用无偏倚的位置偏爱条件反射程序研究中枢阿片受体和外周阿片受体在阿片类药物厌恶效应中的作用。非选择性阿片拮抗剂纳洛酮(NLX)在皮下(SC)和脑室(ICV)给药后对药物相关部位产生条件性厌恶。位置厌恶也被观察到对脑室注射选择性单位拮抗剂CTOP的反应。相反，选择性β-拮抗剂ICI 174,864和选择性β-受体拮抗剂去甲肾上腺素(Nor-BNI)(Icv)无效。中心应用选择性Kappa激动剂U50,488H和强啡肽衍生物E-2078也产生了位置厌恶。对于那些接受测试的阿片配体，ICV后产生地点厌恶所需的剂量比SC给药低得多。这些数据证实了-kappa激动剂和阿片类拮抗剂在药物天然动物中产生厌恶状态，并证明这种影响是中央调节的。此外，与ICI 174,864和NOR-BNI相比，NLX和CTOP产生位置厌恶的能力表明，阿片类拮抗剂的厌恶效应是由于阻断单位受体而产生的。
The role of central versus peripheral opioid receptors in mediating the aversive effects of opioids was examined by use of an unbiased place preference conditioning procedure in rats. The non-selective opioid antagonist naloxone (NLX) produced conditioned aversions for the drug-associated place after subcutaneous (SC) as well as intracerebroventricular (ICV) administration. Place aversions were also observed in response to the ICV administration of the selective .mu.-antagonist CTOP. In contrast, the selective .delta.-antagonist ICI 174,864 and the selective .kappa.-antagonist norbinaltorphimine (nor-BNI) (ICV) were without effect. Place aversions were also produced by central applications of the selective .kappa.-agonist U50,488H and the dynorphin derivative E-2078. For those opioid ligands tested, the doses required to produce place aversions were substantially lower following ICV as compared to SC administration. These data confirm that .kappa.-agonists and opioid antagonists produce aversive states in the drug-native animal and demonstrate that this effect is centrally mediated. Furthermore, the ability of NLX and CTOP, in contrast to both ICI 174,864 and nor-BNI, to produce place aversions suggests that the aversive effects of opioid antagonists result from the blockade of .mu.-receptors.