Broccardo M, Improta G, Negri L, Melchiorri P
Eur J Pharmacol. 1985 Mar 26;110(1):55-61. doi: 10.1016/0014-2999(85)90028-7.
Rats chronically implanted with osmotic minipumps in the left lateral ventricle were used to study the ability of dermorphin to produce tolerance and physical dependence. The development of tolerance, assessed by evaluating the time reduction of analgesia, catalepsy and rigidity, occurred in a dose-dependent fashion over a maximum period of 48 h. After 3 days of peptide infusions into the rat brain, the dependent state was established and was revealed by precipitating the withdrawal syndrome with intraperitoneal naloxone injections. Escape behavior, shaking, salivation and rhynorrhea were the main symptoms, qualitatively similar to those obtained in rats made dependent on morphine. Considering that dermorphin displays strong analgesic activity, the well-known combination of antinociception tolerance and dependence capacities of opiates also seems to be valid for dermorphin.
将渗透微型泵长期植入左侧脑室的大鼠被用于研究皮啡肽产生耐受性和身体依赖性的能力。通过评估镇痛、僵住症和强直的时间缩短来评估耐受性的发展，其在最长48小时内呈剂量依赖性。在向大鼠脑内输注肽3天后，建立了依赖状态，通过腹腔注射纳洛酮引发戒断综合征来揭示。逃避行为、颤抖、流涎和鼻溢是主要症状，在性质上与依赖吗啡的大鼠所出现的症状相似。鉴于皮啡肽具有强大的镇痛活性，阿片类药物众所周知的抗伤害感受耐受性和依赖性能力的组合似乎对皮啡肽也同样适用。
