Cowan A, Rance M J, Blackburn T P
Department of Pharmacology, Temple University School of Medicine, Philadelphia, PA 19140.
NIDA Res Monogr. 1986;75:473-6.
[D-Pen2, D-Pen5]enkephalin (DPDPE), a selective agonist at delta opioid receptors, causes excessive vertical rearing when given icv to rats or s.c. to mice. Tolerance develops to this behaviour. Rats do not rear excessively when injected icv with the following prototype agonists at opioid receptors: DAGO, dynorphin A, U-50488H or SK&F 10047. The incidence of DPDPE-induced rearing is reduced when rats are pretreated s.c. with ICI 174864 (a selective antagonist at delta opioid receptors) (A50 = 0.09 mg/kg) but not by ICI 178173 (an inactive analogue of ICI 174864); this finding suggests that delta binding sites mediate the behaviour. Pretreatment with naloxone attenuates rearing but the antagonism is unimpressive over the dose range tested (0.05-1 mg/kg, s.c.). Low doses of haloperidol (A50 = 0.05 mg/kg, s.c.) antagonize the rearing. Dopamine may therefore mediate the behaviour through delta receptor modulation of dopamine release. The practical gain from this study is as follows: a simple, discriminating test is now available for evaluating novel delta agonists and antagonists in vivo.
[D-青霉胺2，D-青霉胺5]脑啡肽（DPDPE）是一种δ阿片受体的选择性激动剂，当脑室内注射给大鼠或皮下注射给小鼠时，会导致过度的垂直竖毛行为。对这种行为会产生耐受性。当给大鼠脑室内注射以下阿片受体原型激动剂时：DAGO、强啡肽A、U-50488H或SK&F 10047，大鼠不会过度竖毛。当大鼠皮下预先注射ICI 174864（一种δ阿片受体的选择性拮抗剂）（半数有效量=0.09毫克/千克）时，DPDPE诱导的竖毛发生率降低，但ICI 178173（ICI 174864的无活性类似物）则无此作用；这一发现表明δ结合位点介导了这种行为。用纳洛酮预处理可减弱竖毛行为，但在所测试的剂量范围（0.05-1毫克/千克，皮下注射）内，拮抗作用不明显。低剂量的氟哌啶醇（半数有效量=0.05毫克/千克，皮下注射）可拮抗竖毛行为。因此，多巴胺可能通过δ受体对多巴胺释放的调节来介导这种行为。这项研究的实际收获如下：现在有了一种简单、有鉴别力的试验，可用于在体内评估新型δ激动剂和拮抗剂。
