Korkmaz S, Carlsson S, Wahlström G
Department of Pharmacology, Umeå University, Sweden.
Eur Neuropsychopharmacol. 1998 Aug;8(3):175-81. doi: 10.1016/s0924-977x(97)00058-8.
Rats were treated with lorazepam for four days (six times 2 mg kg(-1)) at the ages of 71, 118, 163 and 210 days. Increased excitation (physical dependence) in the withdrawal period was tested several times during 14 days with hexobarbital in an EEG threshold test. Lorazepam could induce physical dependence usually with a maximum (20% of the controls) on day four of withdrawal, but the age was a critical variable. A dose-response relationship with regard to lorazepam (0.5, 1, 2 mg kg(-1)) was found at 71 days but a more complicated pattern was found at 118 days of age. The rats treated with lorazepam 2 mg kg(-1) at the ages of either 71 and 118 days were given a treatment again with lorazepam 2 mg kg(-1) three months later. Compared with age-matched untreated rats, previous drug exposure influenced the pattern of increased excitation indicating a carry-over effect even after such a recovery period.
在71、118、163和210日龄时，给大鼠连续四天（六次，每次2 mg kg⁻¹）注射劳拉西泮。在停药期，通过脑电图阈值试验，用己巴比妥多次测试停药期兴奋度增加（身体依赖性）的情况。劳拉西泮通常可诱导身体依赖性，在停药第四天时依赖性最强（为对照组的20%），但年龄是一个关键变量。在71日龄时发现了劳拉西泮（0.5、1、2 mg kg⁻¹）的剂量反应关系，但在118日龄时发现了更复杂的模式。在71日龄和118日龄时接受2 mg kg⁻¹劳拉西泮治疗的大鼠，三个月后再次接受2 mg kg⁻¹劳拉西泮治疗。与年龄匹配的未治疗大鼠相比，先前的药物暴露影响了兴奋度增加的模式，表明即使经过这样一个恢复期仍有残留效应。
