Djeridane Yasmina, Lemmer Björn, Touitou Yvan
Faculté de Médecine, Pitié-Salpêtrière, Service de Biochimie Médicale et Biologie Moléculaire and INSERM U713, Paris, France.
Chronobiol Int. 2005;22(6):975-85. doi: 10.1080/07420520500395094.
The present study investigates the effects of a chronic administration of diazepam, a benzodiazepine widely used as an anxiolytic, on locomotor activity and body core temperature rhythms in male Wistar rats housed under 12 : 12 light : dark (LD) cycle conditions. Diazepam was administered subcutaneously for 3 wks in a dosage of 3 mg/kg body weight/day, 1 h before the onset of darkness. Diazepam increased the level of locomotor activity from the first day until the end of treatment, and also increased the amplitude of the activity circadian rhythm, but only on the third wk of treatment. Diazepam exerted no effects on the length of the period and did not affect the phase of the locomotor activity rhythm. The body temperature rhythm of rats was affected neither by short-term (a single injection) nor by long-term (every day for 3 wks) diazepam treatment. Diazepam lacked effect on body core temperature even on the first day of administration, thereby ruling out the possibility of drug tolerance development. The fact that diazepam affects locomotor activity, but not core body temperature, suggests that different mechanisms mediate the actions of diazepam on locomotor activity and on core body temperature.
本研究调查了长期给予地西泮（一种广泛用作抗焦虑药的苯二氮䓬类药物）对处于12:12光照:黑暗（LD）循环条件下的雄性Wistar大鼠的运动活动和体核温度节律的影响。地西泮以3毫克/千克体重/天的剂量在黑暗开始前1小时皮下注射，持续3周。从治疗第一天到结束，地西泮均增加了运动活动水平，并且在治疗的第三周增加了活动昼夜节律的幅度。地西泮对周期长度没有影响，也不影响运动活动节律的相位。大鼠的体温节律既不受短期（单次注射）地西泮治疗的影响，也不受长期（每天注射，持续3周）地西泮治疗的影响。即使在给药的第一天，地西泮对体核温度也没有影响，从而排除了产生药物耐受性的可能性。地西泮影响运动活动但不影响体核温度这一事实表明，不同的机制介导了地西泮对运动活动和体核温度的作用。
