Eisenberg R M
Department of Pharmacology, University of Minnesota-Duluth, School of Medicine 55812.
Pharmacol Biochem Behav. 1994 Apr;47(4):943-6. doi: 10.1016/0091-3057(94)90300-x.
Previous work in our laboratory has shown that DAMGO (ICV) will cause an elevation in plasma corticosterone (CS). The effect was blocked by pretreatment with beta-FNA but not by naloxonazine, suggesting indirectly that DAMGO's effect was via a mu 2-opioid receptor. TRIMU-5, a mu 2 agonist/mu 1 antagonist, was tested in a similar series of experiments to show more directly that the effect of DAMGO to increase plasma CS was via the mu 2 receptor. Experiments were conducted on conscious, unrestrained, male Sprague-Dawley rats with chronic IV catheters and ICV cannula guides allowing for serial blood sampling and drug injection into the right lateral ventricle. During this process, animals remained isolated in sound-attenuated one-way vision boxes. TRIMU-5, 50 micrograms, produced a sustained increase in plasma CS for a 3-h period. The response peaked at 30 min, showing a plasma CS level of 19.7 +/- 1.4 micrograms/dl. A lower dose, 10 micrograms, did not produce a significant response. A higher dose, 100 micrograms, produced an elevated hormone response in a pilot study but was lethal in half the animals. The plasma CS increase was blocked by pretreatment with beta-FNA, 20 micrograms ICV, given 18 h before TRIMU-5, but was unaffected by naloxonazine pretreatment, 20 mg/kg i.v., also administered 18 h before TRIMU-5. These data confirm our earlier conclusion that the effect of DAMGO to elevate plasma CS was through a mu 2-opioid receptor.
我们实验室之前的研究表明，脑室内注射DAMGO会导致血浆皮质酮（CS）水平升高。β-FNA预处理可阻断该效应，但纳洛酮嗪则不能，这间接表明DAMGO的作用是通过μ2阿片受体介导的。TRIMU-5是一种μ2激动剂/μ1拮抗剂，在一系列类似实验中进行了测试，以更直接地证明DAMGO增加血浆CS的作用是通过μ2受体介导的。实验在清醒、不受约束的雄性Sprague-Dawley大鼠身上进行，这些大鼠带有慢性静脉导管和脑室内插管导向装置，以便进行连续采血和向右侧脑室注射药物。在此过程中，动物被单独置于隔音的单向视觉箱中。50微克的TRIMU-5可使血浆CS在3小时内持续升高。反应在30分钟时达到峰值，血浆CS水平为19.7±1.4微克/分升。较低剂量10微克未产生显著反应。较高剂量100微克在一项初步研究中产生了升高的激素反应，但在一半的动物中是致命的。在注射TRIMU-5前18小时脑室内注射20微克β-FNA预处理可阻断血浆CS的升高，但在注射TRIMU-5前18小时静脉注射20毫克/千克纳洛酮嗪预处理则无影响。这些数据证实了我们之前的结论，即DAMGO升高血浆CS的作用是通过μ2阿片受体介导的。
