Ahlenius S, Ericson E L, Högberg K, Wijkström A
Department of Neuropharmacology, Astra Research Centre AB, Södertälje, Sweden.
Pharmacol Toxicol. 1991 Apr;68(4):302-9. doi: 10.1111/j.1600-0773.1991.tb01243.x.
Male Sprague-Dawley rats were treated with the dopamine (DA) D2 receptor blocking agent raclopride 0.5 or 8.0 mg kg-1 subcutaneously (1.0 and 16.0 mumol kg-1, respectively), twice daily for 21 days. The animals treated with raclopride gained weight at the same rate as saline controls, and gross observation did not indicate any behavioural abnormalities due to the subchronic raclopride treatment. Possible changes in brain DA receptor sensitivity due to prolonged blockade of DA receptors were evaluated in behavioural and biochemical models. There were no effects on locomotor activity, as observed by means of photobeam-equipped activity cages, 24 hr or 72 hr after withdrawal of 0.5 or 8.0 mg kg-1 subchronic raclopride treatment. Twenty-four hr after withdrawal of the raclopride treatment there was an increased post-synaptic DA receptor sensitivity as evidenced by increased behavioural and biochemical responses to apomorphine, and by an attenuated response to acute raclopride treatment, 0.1 mg kg-1. Thus, there was an increase in locomotor activity by the apomorphine treatment in animals pretreated with the 8 mg kg-1 dose, as compared to the response obtained in saline controls. Furthermore, the suppression of locomotor activity in saline controls produced by acute raclopride treatment was dose-dependently antagonized by the raclopride pretreatment and this also applied to the increase in striatal DOPAC levels produced by acute raclopride treatment. Finally, there was an increased DA receptor sensitivity presynaptically as evidenced by an enhanced effect on striatal DOPA levels by apomorphine in rats treated with NSD 1015 and reserpine.(ABSTRACT TRUNCATED AT 250 WORDS)
雄性Sprague-Dawley大鼠皮下注射多巴胺（DA）D2受体阻断剂雷氯必利，剂量分别为0.5或8.0 mg/kg（分别为1.0和16.0 μmol/kg），每日两次，共21天。接受雷氯必利治疗的动物体重增加速度与生理盐水对照组相同，大体观察未发现由于亚慢性雷氯必利治疗导致的任何行为异常。通过行为和生化模型评估了由于DA受体长期阻断导致的脑DA受体敏感性的可能变化。在撤去0.5或8.0 mg/kg亚慢性雷氯必利治疗后24小时或72小时，通过配备光电束的活动笼观察，未发现对运动活性有影响。撤去雷氯必利治疗24小时后，突触后DA受体敏感性增加，这表现为对阿扑吗啡的行为和生化反应增强，以及对急性雷氯必利治疗（0.1 mg/kg）的反应减弱。因此，与生理盐水对照组相比，用8 mg/kg剂量预处理的动物经阿扑吗啡治疗后运动活性增加。此外，雷氯必利预处理剂量依赖性地拮抗了急性雷氯必利治疗对生理盐水对照组运动活性的抑制作用，这也适用于急性雷氯必利治疗引起的纹状体3,4-二羟基苯乙酸（DOPAC）水平的升高。最后，用NSD 1015和利血平处理的大鼠中，阿扑吗啡对纹状体左旋多巴（DOPA）水平的增强作用表明突触前DA受体敏感性增加。（摘要截短于250字）
