Churchill L, Roques B P, Kalivas P W
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman, USA.
Psychopharmacology (Berl). 1995 Aug;120(3):347-55. doi: 10.1007/BF02311183.
The aim of this study is to analyze further the opioid receptor subtypes involved in the augmentation of behavioral activity after dopamine depletion in the nucleus accumbens of rats. Initially, the opioid receptors involved in the augmentation of locomotion produced by endogenous opioids were evaluated by microinjection of kelatorphan, an inhibitor of proteolytic enzymes that inactivates enkephalin, with or without specific antagonists for mu 1 or delta-opioid receptors, naloxonazine or naltrindole, respectively. Kelatorphan produced a dose-dependent increase in horizontal photocell counts and vertical movements. At all doses examined the behavioral response was augmented in rats sustaining accumbal dopamine lesions. The augmentation in dopamine-depleted rats was partially blocked by naloxonazine or naltrindole. Since the motor stimulant response to intra-accumbens microinjection of the delta-opioid agonist, [D-penicillamine2,5]-enkephalin, was not augmented in a previous study, we tested the behavioral response to a new endogenous delta-opioid agonist, [D-Ala2] deltorphin I. The locomotor response to deltorphin was slightly augmented in dopamine-depleted rats. These data suggest that the augmentation in the motor response elicited by endogenous opioids after dopamine lesions in the nucleus accumbens involves both mu 1, and delta-opioid receptors.
本研究的目的是进一步分析参与大鼠伏隔核多巴胺耗竭后行为活动增强的阿片受体亚型。最初，通过分别注射蛋白酶抑制剂凯拉托啡（一种可使脑啡肽失活的蛋白酶抑制剂），以及μ1或δ阿片受体的特异性拮抗剂纳洛嗪或纳曲吲哚，来评估内源性阿片类物质所引起的运动增强中涉及的阿片受体。凯拉托啡使水平光电管计数和垂直运动呈剂量依赖性增加。在所有检测剂量下，伏隔核多巴胺损伤大鼠的行为反应均增强。多巴胺耗竭大鼠的反应增强被纳洛嗪或纳曲吲哚部分阻断。由于在之前的一项研究中，对伏隔核内微量注射δ阿片受体激动剂[D-青霉胺2,5]-脑啡肽的运动刺激反应并未增强，因此我们测试了对一种新的内源性δ阿片受体激动剂[D-Ala2]强啡肽I的行为反应。多巴胺耗竭大鼠对强啡肽的运动反应略有增强。这些数据表明，伏隔核多巴胺损伤后内源性阿片类物质引起的运动反应增强涉及μ1和δ阿片受体。
