OPIATE ABUSE, REWARD AND AGING

描述(申请人提供)：有证据表明年长的患者 与年轻患者相比，需要更少的吗啡才能有效止痛， 说明止痛剂的效力随年龄增长而增加。同时服用鸦片 吸毒者中的使用量似乎随着年龄的增长而下降，这表明 鸦片类药物的享乐性效力可能会随着年龄的增长而减弱。建议数 实验将确定是否有不同的享乐效果 吗啡是一种典型的鸦片类药物，通过吗啡对 对年轻人进行脑电刺激的奖励阈值， 中老年大鼠。这些结果将与 由逃避阈值的变化确定对吗啡的镇痛反应 来自三个年龄组的大鼠的厌恶电刺激。 因为大鼠很快就会对吗啡诱导的刻板印象咬伤敏感 以及运动行为和这种敏感化可能模拟了大脑的变化 与阿片类成瘾者的复发有关；发展和表达 将比较三组受试者的吗啡致敏行为。 此外，因为衰老可能会改变药物分布和消除的模式 率，吗啡的药代动力学将被比较在这些不同的 老年群体。据我们所知，拟议中的实验将是第一个 考察阿片类药物的止痛和享乐作用之间的关系 和衰老。这项研究的发现可能对这两个方面都有影响 老年人的疼痛管理和阿片类药物滥用。

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.