AGE-RELATED DIFFERENCES IN OPIOID SENSITIVITY

阿片类药物滥用研究的一个主要目标是确定导致阿片类药物滥用的各种生物学、药理学和情境因素。 这项研究的一个重要组成部分是检查受试人群中阿片类药物敏感性的差异。 这项研究表明，对阿片类药物影响的敏感性往往因年龄组而异。 虽然造成这些差异的机制尚未完全了解，但有数据表明阿片受体生理学中与年龄相关的改变可能起作用。 这种改变可能会影响个体对阿片类药物的反应，并可能导致受试者群体之间阿片类药物敏感性的巨大差异。 本研究项目的目的是检查与年龄相关的抗伤害性敏感性差异（即，镇痛）的作用μ阿片类药物在温水，尾部撤回程序。 在该过程中，将大鼠束缚，并记录从50和55 ℃水中取出其尾巴的时间。 在实验I中，将在年轻（3个月）、成熟（12个月）和老年（24个月）大鼠中检查几种μ阿片类药物的抗伤害感受作用。 本实验的目的是量化对μ阿片类药物的抗伤害感受作用的敏感性的年龄相关差异，并确定这些差异是否受到伤害感受刺激强度的影响（即，水温）和/或测试药物的内在功效（即，其在结合到其受体位点后引发细胞应答的能力）。 在实验II中，将在三个年龄组中检查对μ阿片类药物作用的耐受性和交叉耐受性的发展。 在尾部戒断程序中，将在长期吗啡给药方案（20 mg/kg b.i.d.）之前和期间检查几种μ阿片类药物的抗伤害感受作用。 本实验的目的是量化与年龄相关的差异的速度和幅度的耐受性发展的μ阿片类药物的影响，并确定这些差异是否受到阿片类药物的内在疗效。

A major goal of opioid abuse research is to identify the various biological, pharmacological and situational factors that contribute to opioid abuse. One important component of this research involves examining differences in opioid sensitivity across subject populations. This research has shown that sensitivity to the effects of opioids often differs across age groups. Although the mechanisms responsible for these differences are not fully understood, there are data indicating that age-related alterations in opioid receptor physiology may play a role. Such alterations may influence an individual's response to opioids, and may result in large differences in opioid sensitivity across subject populations. The purpose of this research project is to examine age-related differences in sensitivity to the antinociceptive (i.e., analgesic) effects of mu opioids in the warm-water, tail-withdrawal procedure. In this procedure, rats are restrained and the latencies to remove their tails from 50 and 55 C water are recorded. In experiment I, the antinociceptive effects of several mu opioids will be examined in young (3 months), mature, (12 months) and aged (24 months) rats. The aim of this experiment is to quantify age- related differences in sensitivity to the antinociceptive effects of mu opioids, and to determine if these differences are influenced by the intensity of the nociceptive stimulus (i.e., water temperature) and/or the intrinsic efficacy of the test drug (i.e., its ability to initiate a cellular response after binding to its receptor site). In experiment II, the development of tolerance and cross-tolerance to the effects of mu opioids will be examined across the three age groups. In the tail-withdrawal procedure, the antinociceptive effects of several mu opioids will be examined before and during a regimen of chronic morphine administration (20 mg/kg b.i.d.). The aim of this experiment is to quantify age-related differences in the speed and magnitude to which tolerance develops to the effects of mu opioids, and to determine if these differences are influenced by an opioid's intrinsic efficacy.