Neisewander J L, Nonneman A J, Rowlett J K, Bardo M T
Department of Psychology, University of Kentucky, Lexington 40506.
Neurobiol Aging. 1994 Jan-Feb;15(1):91-7. doi: 10.1016/0197-4580(94)90148-1.
Chronic administration of opiate antagonists produces an increase in the density of opiate receptors, as well as an enhanced sensitivity to the analgesic and locomotor depressant effects of morphine. The present study assessed whether aging alters these regulatory processes. Young (3-4 months), middle-aged (10-11 months), and senescent (25-30 months) rats were implanted subdermally with slow-release naltrexone pellets or were given sham surgery. The pellets were removed 10 days later. Twenty-four hours after pellet removal, morphine-induced (5 mg/kg, SC) analgesia and locomotor activity were assessed. Young and middle-aged rats treated with naltrexone showed enhanced sensitivity to the analgesic and locomotor activity depressant effects of morphine relative to age-matched controls. In contrast, senescent rats treated with naltrexone did not differ from age-matched controls in their response to morphine. The density of opiate receptors labeled with 3H-naloxone was measured in the anterior striatum. Both young and senescent rats treated with naltrexone exhibited an increase in opiate receptor density relative to age-matched controls. The results indicate that senescent rats are capable of up-regulating opiate receptors following chronic naltrexone treatment but do not exhibit the corresponding functional supersensitivity to morphine.
长期给予阿片类拮抗剂会使阿片受体密度增加，同时对吗啡的镇痛和运动抑制作用的敏感性增强。本研究评估了衰老是否会改变这些调节过程。将年轻（3 - 4个月）、中年（10 - 11个月）和老年（25 - 30个月）大鼠皮下植入缓释纳曲酮微丸或进行假手术。10天后取出微丸。取出微丸24小时后，评估吗啡诱导的（5毫克/千克，皮下注射）镇痛和运动活性。与年龄匹配的对照组相比，用纳曲酮治疗的年轻和中年大鼠对吗啡的镇痛和运动活性抑制作用表现出更高的敏感性。相比之下，用纳曲酮治疗的老年大鼠对吗啡的反应与年龄匹配的对照组没有差异。在前纹状体中测量用³H - 纳洛酮标记的阿片受体密度。与年龄匹配的对照组相比，用纳曲酮治疗的年轻和老年大鼠均表现出阿片受体密度增加。结果表明，老年大鼠在长期纳曲酮治疗后能够上调阿片受体，但对吗啡没有表现出相应的功能超敏反应。
