Fanselow M S, Calcagnetti D J, Helmstetter F J
Department of Psychology, Dartmouth College, Hanover, New Hampshire.
J Pharmacol Exp Ther. 1989 Sep;250(3):825-30.
When rats are returned to an environment in which they previously received electric shock they show a reduction in sensitivity to painful stimuli. This conditional fear-induced analgesia was measured using the formalin test. The octapeptide Cys2Tyr3Orn5Pen7-amide (CTOP; 0, 10, 40 and 160 ng/rat) dose-dependently reversed conditional analgesia when administered i.c.v. The 40-ng dose partially attenuated fear-induced analgesia, whereas the 160-ng dose reversed it completely. Using similar procedures, CTOP was tested for its ability to reverse the analgesia produced by i.c.v. administered [D-Ala2,-NMPhe4, Glyol5]-enkephalin, [D-Pen2,D-Pen5]-enkephalin and U50488H, which are highly selective opioid agonists at mu, delta and kappa receptors, respectively. At 40 ng/rat, CTOP reversed the analgesia produced by the mu selective ligand but not that produced by the delta ligand or the kappa ligand. At 80 ng CTOP antagonized the analgesia produced both by both enkephalin analogs but not U50488H. Nor-binaltorphimine (0, 1, 3, 10 and 30 micrograms/rat) had no effect on conditional analgesia. However, the 10- and 30-micrograms doses could reverse completely the analgesia produced by U50488H. Therefore, it appears that mu and delta, but not kappa receptors, are involved in this opioid form of stress-induced analgesia.
当大鼠被放回它们之前遭受过电击的环境中时，它们对疼痛刺激的敏感性会降低。这种条件性恐惧诱导的镇痛作用通过福尔马林试验来测定。八肽Cys2Tyr3Orn5Pen7-酰胺（CTOP；0、10、40和160纳克/只大鼠）经脑室内给药时，剂量依赖性地逆转了条件性镇痛作用。40纳克的剂量部分减弱了恐惧诱导的镇痛作用，而160纳克的剂量则完全逆转了它。使用类似的程序，测试了CTOP逆转脑室内注射[D-丙氨酸2，-N-甲基苯丙氨酸4，甘油5]-脑啡肽、[D-青霉胺2，D-青霉胺5]-脑啡肽和U50488H所产生的镇痛作用的能力，这些分别是μ、δ和κ受体的高选择性阿片类激动剂。在40纳克/只大鼠的剂量下，CTOP逆转了μ选择性配体所产生的镇痛作用，但没有逆转δ配体或κ配体所产生的镇痛作用。在80纳克时，CTOP拮抗了两种脑啡肽类似物所产生的镇痛作用，但没有拮抗U50488H所产生的镇痛作用。去甲二氢吗啡酮（0、1、3、10和30微克/只大鼠）对条件性镇痛作用没有影响。然而，10微克和30微克的剂量可以完全逆转U50488H所产生的镇痛作用。因此，似乎μ和δ受体，而不是κ受体，参与了这种阿片类形式的应激诱导镇痛作用。
