Jewett D C, Mosberg H I, Woods J H
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
Psychopharmacology (Berl). 1996 Oct;127(3):225-30.
The present study assessed the discriminative stimulus effects of the delta-opioid agonist [D-Pen2-D-Pen5]enkephalin (DPDPE) in pigeons. Food-restricted pigeons were trained to discriminate between i.c.v injections of 100 micrograms [D-Pen2-D-Pen5]enkephalin (DPDPE) and saline in a two-key operant procedure; acquisition of discriminative control was rapid (14-28 daily sessions). [D-Ser2, Leu5, Thr6]enkephalin (DSLET) and [D-Ala2]deltorphin II, peptides selective for delta-opioid receptors, produced discriminative stimulus effects similar to DPDPE, and were approximately equipotent to DPDPE. The non-peptidic, delta-opioid agonist BW373U86 (0.032-100 mg/kg, i.m.) partially generalized to DPDPE. The kappa-opioid agonist U69,593 (0.01-1 mg/kg, i.m.), and the mu-opioid agonists, DAMGO (0.1-3.2 micrograms, i.c.v) and morphine (1-10 mg/kg, i.m.), did not produce discriminative stimulus effects similar to DPDPE, up to doses that markedly decreased response rates. Naltrindole (0.1 mg/kg. i.m.), an antagonist selective for delta-opioid receptors, produced approximately a 30-fold reduction in the potency of DPDPE. DPDPE's discriminative stimulus effect in pigeons appears to be mediated through a delta-opioid receptor; this effect may provide a procedure for assessing delta-opioid receptor function in vivo.
本研究评估了δ-阿片受体激动剂[D-青霉胺2,D-青霉胺5]脑啡肽(DPDPE)对鸽子的辨别刺激效应。对食物受限的鸽子进行训练,使其在双键操作性程序中区分脑室内注射100微克[D-青霉胺2,D-青霉胺5]脑啡肽(DPDPE)和生理盐水;辨别性控制的获得很快(每天14 - 28次训练)。[D-丝氨酸2,亮氨酸5,苏氨酸-6]脑啡肽(DSLET)和[D-丙氨酸2]强啡肽II,这两种对δ-阿片受体有选择性的肽,产生了与DPDPE相似的辨别刺激效应,且与DPDPE的效力大致相当。非肽类δ-阿片受体激动剂BW373U86(0.032 - 100毫克/千克,肌肉注射)部分泛化至DPDPE。κ-阿片受体激动剂U69,593(0.01 - 1毫克/千克,肌肉注射)以及μ-阿片受体激动剂DAMGO(0.1 - 3.2微克,脑室内注射)和吗啡(1 - 10毫克/千克,肌肉注射),在剂量达到显著降低反应率时,均未产生与DPDPE相似的辨别刺激效应。δ-阿片受体选择性拮抗剂纳曲吲哚(0.1毫克/千克,肌肉注射)使DPDPE的效力降低了约30倍。DPDPE对鸽子的辨别刺激效应似乎是通过δ-阿片受体介导的;这种效应可能为评估体内δ-阿片受体功能提供一种方法。