OPIATE ABUSE, REWARD AND AGING

阿片类药物滥用、奖励和老龄化

• 批准号: 6515820
• 负责人: CONAN KORNETSKY
• 金额: $ 16.3万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-15 至 2004-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6515820
• 关键词: age difference; aging; analgesia; behavioral habituation /sensitization; drug abuse; drug addiction; electrostimulus; endogenous opioid; laboratory rat; morphine; pharmacokinetics; reinforcer; substance abuse related behavior

DESCRIPTION (provided by applicant): There is evidence that older patients require less morphine for effective analgesic relief than younger patients, suggesting that analgesic potency increases with age. At the same time opiate use in addict populations appear to decline as a function of age, suggesting that the hedonic potency of opiates may decrease with age. The proposed experiments will determine if there are differences in the hedonic effects of morphine, the prototypic opiate, as measured by morphine's effect on the threshold for rewarding electrical intracranial stimulation in young, middle-aged and aged rats. These results will be compared to changes in the analgesic response to morphine as determined by threshold changes in escape from aversive electrical brain stimulation in the three age groups of rats. Because rats quickly become sensitized to morphine-induced stereotypic biting and locomotor behavior and this sensitization may be modeling brain changes associated with relapse in the opiate addict; the development and expression of morphine sensitized behavior will be compared in the three group of subjects. Also, because aging may alter patterns of drug distribution and elimination rates, the pharmacokinetics of morphine will be compared in these different aged groups. To our knowledge, the proposed experiments will be the first to examine the relationship between the analgesic and hedonic effects of opiates and aging. The findings of this study may have implications with regard to both pain management and opiate abuse in the elderly.

描述（由申请人提供）：有证据表明老年患者 与年轻患者相比，需要更少的吗啡以使有效的镇痛药缓解， 表明镇痛效力随着年龄的增长而增加。同时鸦片 在成瘾者中的使用似乎是年龄的函数，表明 阿片类药物的享乐效力可能会随着年龄的增长而降低。提议 实验将确定享乐效应是否存在 吗啡，原型鸦片，如吗啡对吗啡对 奖励年轻的颅内刺激的阈值， 中年和老鼠。这些结果将与变化进行比较 按偏度阈值变化确定的对吗啡的镇痛反应 从三个年龄组的大鼠厌恶性电脑刺激中。 因为大鼠迅速对吗啡引起的刻板印象敏感 运动行为和这种敏化可能正在建模大脑的变化 与鸦片瘾君子的复发有关；的发展和表达 在三组受试者中，将比较吗啡敏化行为。 另外，由于衰老可能会改变药物分布和消除的模式 在这些不同的不同的情况下，将比较吗啡的药代动力学 老年人组。据我们所知，拟议的实验将是第一个 检查阿片类药物的镇痛和享乐效应之间的关系 和老化。这项研究的发现可能对两者都有影响 老年人的疼痛管理和鸦片虐待。