Ceger P, Kuhn C M
Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA.
Psychopharmacology (Berl). 2000 Jun;150(3):253-9. doi: 10.1007/s002130000413.
Treatment of developing rat pups with morphine (MOR) causes the development of physical dependence, but the relationship of the withdrawal syndrome to the duration/intensity of treatment has not been described.
The purpose of the present study was to characterize the emergence of various behavioral components of withdrawal in neonatal rats, and to develop a useful measure of overall intensity of withdrawal (OIW).
Rat pups were treated with morphine (MOR) (20 mg/kg, SC, b.i.d.) for 0-5 days. On postnatal day 10 (P10), animals received saline (SAL) or a challenge dose of MOR (25 mg/kg). Withdrawal was precipitated with naloxone HCl (NAL) (0.1, 0.5 or 2.5 mg/kg) 2 h after the MOR injection, and behaviors were quantitated for 10 min. To investigate the ability of clonidine HCl (CLON) to suppress withdrawal, pups were treated for 0 or 5 days with MOR, given a MOR challenge and either SAL or CLON (0.2 mg/kg), followed by SAL or NAL (2.5 mg/kg, SC). To evaluate endocrine components of withdrawal, growth hormone responses to withdrawal were examined.
The OIW and NAL-induced GH suppression increased with increasing NAL dose and duration of morphine treatment. However, individual behaviors showed differing patterns of expression. Clonidine decreased the severity of tremor and reduced the OIW.
These results demonstrate that the intensity of neonatal opiate withdrawal is related to the duration and intensity of treatment. The profile of observed withdrawal behaviors may reflect the involvement of the noradrenergic system.
用吗啡（MOR）处理发育中的大鼠幼崽会导致身体依赖性的形成，但戒断综合征与治疗持续时间/强度之间的关系尚未得到描述。
本研究的目的是描述新生大鼠戒断的各种行为成分的出现情况，并开发一种有用的戒断总体强度（OIW）测量方法。
大鼠幼崽用吗啡（MOR）（20mg/kg，皮下注射，每日两次）处理0至5天。在出生后第10天（P10），动物接受生理盐水（SAL）或一剂挑战剂量的吗啡（25mg/kg）。在吗啡注射后2小时，用盐酸纳洛酮（NAL）（0.1、0.5或2.5mg/kg）诱发戒断，并对行为进行10分钟的定量。为了研究盐酸可乐定（CLON）抑制戒断的能力，幼崽用吗啡处理0天或5天，给予吗啡挑战，然后给予生理盐水或可乐定（0.2mg/kg），接着给予生理盐水或纳洛酮（2.5mg/kg，皮下注射）。为了评估戒断的内分泌成分，检查了生长激素对戒断的反应。
戒断总体强度（OIW）和纳洛酮诱导的生长激素抑制随着纳洛酮剂量和吗啡治疗持续时间的增加而增加。然而，个体行为表现出不同的表达模式。可乐定降低了震颤的严重程度并降低了戒断总体强度（OIW）。
这些结果表明，新生儿阿片类药物戒断的强度与治疗的持续时间和强度有关。观察到的戒断行为特征可能反映了去甲肾上腺素能系统的参与。
