Riffee W H, Wilcox R E, Smith R V
Res Commun Chem Pathol Pharmacol. 1978 Nov;22(2):301-12.
A preliminary evaluation of behavioral arousal in mice, as a model system for quantifying activity of presumptive antiparkinsonian and antischizophrenic agents, was made. In experiments not yet published, we have observed stereotypic cage climbing induced by two aporphines (apomorphine, APO; and N-n-propylnoraporphine, NPA) to be specifically dopaminergic. Time of peak effect was found to be 15--30 min and an ED50 of approximately 4 mg/kg was established for both drugs. In the present study we have investigated the activity of APO and NPA on behavioral arousal. As measured by electromagnetic sensors, behavioral arousal reflects several responses including spontaneous locomotor activity and repetitive movements (e.g., grooming and rearing). The procedures which we have employed minimize artifacts due to handling and injection routines while maximizing our ability to observe time of peak effect (based on blood levels). Dose and time response analyses of APO and NPA (i.p.) demonstrated a time of peak effect from 15--30 min and ED50 values of 3.0 and 2.5 mg/kg for APO and NPA, respectively. The results of our experiments show that for a 90 min period over the 1--10 mg/kg dose range employed, APO exhibits a linear dose response relationship whereas that for NPA is sigmoidal. Similarities in time of peak effect and ED50s for the two aporphines in stereotypic cage-climbing and behavioral arousal experiments suggest that the behavioral arousal induced by APO and NPA may be dopaminergically mediated.
对小鼠行为觉醒进行了初步评估,将其作为一种模型系统,用于量化假定的抗帕金森病和抗精神分裂症药物的活性。在尚未发表的实验中,我们观察到两种阿朴啡(阿扑吗啡,APO;和N - 正丙基去甲阿朴啡,NPA)诱导的刻板笼内攀爬具有特异性多巴胺能作用。发现两种药物的峰值效应时间为15 - 30分钟,且ED50约为4 mg/kg。在本研究中,我们研究了APO和NPA对行为觉醒的活性。通过电磁传感器测量,行为觉醒反映了包括自发运动活动和重复运动(如梳理毛发和竖毛)在内的多种反应。我们采用的程序将因处理和注射程序导致的假象降至最低,同时最大程度地提高我们观察峰值效应时间(基于血药浓度)的能力。对APO和NPA(腹腔注射)的剂量和时间反应分析表明,峰值效应时间为15 - 30分钟,APO和NPA的ED50值分别为3.0和2.5 mg/kg。我们的实验结果表明,在所采用的1 - 10 mg/kg剂量范围内,APO在90分钟内呈现线性剂量反应关系,而NPA的剂量反应关系呈S形。在刻板笼内攀爬和行为觉醒实验中,两种阿朴啡的峰值效应时间和ED50的相似性表明,APO和NPA诱导的行为觉醒可能是由多巴胺能介导的。