Eisenberg R M, Sparber S B
J Pharmacol Exp Ther. 1979 Nov;211(2):364-9.
Changes in plasma corticosterone levels have been utilized as a sensitive and reliable indicator of opiate withdrawal. By using rats prepared with chronic indwelling i.v. catheters, drug injections and sequential blood sampling were accompanied in conscious undisturbed animals. Acute administration of levorphanol tartrate (LT) at 0.5, 1.0 or 2.0 mg/kg b.wt. caused an elevation in circulating corticosterone. With the lowest dose of LT, hormone levels returned to pretreatment values by 180 min. Naloxone hydrochloride (NX), 0.4 mg/kg, administered 3 hr after pretreatment with LT, 0.5 mg/kg, produced a significant elevation in plasma corticosterone. In contrast, animals pretreated with saline did not show the same increase in hormone levels after NX. NX, administered at several doses, along with LT, suppressed the plasma corticosterone increase which is normally observed when LT is given acutely. When NX is administered at sufficient dosage, along with LT pretreatment, the subsequent administration of the antagonist did not elicit the withdrawal response. These data indicate that a similar increase in plasma corticosterone, upon challenge with NX after a single dose of morphine, generalizes to other opiates. Blockade of the initial rise in plasma corticosterone and subsequent increase upon injection of the antagonist speak to the probability of the responses being related and opiate specific.
血浆皮质酮水平的变化已被用作阿片类药物戒断的敏感且可靠指标。通过使用植入慢性静脉导管的大鼠，在清醒且未受干扰的动物身上进行药物注射并连续采血。以0.5、1.0或2.0mg/kg体重的剂量急性给予酒石酸左啡诺（LT）会导致循环皮质酮升高。使用最低剂量的LT时，激素水平在180分钟时恢复到预处理值。在用0.5mg/kg的LT预处理3小时后给予0.4mg/kg的盐酸纳洛酮（NX），会使血浆皮质酮显著升高。相比之下，用生理盐水预处理的动物在给予NX后激素水平没有出现同样的升高。与LT一起给予几种剂量的NX，抑制了急性给予LT时通常观察到的血浆皮质酮升高。当以足够剂量与LT预处理一起给予NX时，随后给予拮抗剂不会引发戒断反应。这些数据表明，在单剂量吗啡后用NX激发时，血浆皮质酮的类似升高也适用于其他阿片类药物。血浆皮质酮最初的升高以及注射拮抗剂后的后续升高被阻断，这表明这些反应相关且具有阿片类药物特异性的可能性。
