SYNERGISTIC BEHAVIORAL-EFFECTS OF DOPAMINE-D1 AND DOPAMINE-D2 RECEPTOR AGONISTS ARE DETERMINED BY CIRCADIAN-RHYTHMS
SYNERGISTIC BEHAVIORAL-EFFECTS OF DOPAMINE-D1 AND DOPAMINE-D2 RECEPTOR AGONISTS ARE DETERMINED BY CIRCADIAN-RHYTHMS
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DOI：
10.1016/0014-2999(92)90616-c
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发表时间：
1992-04-29
影响因子：
5
通讯作者：
YAMADA, N
中科院分区：
文献类型：
--
作者：
MARTINIVERSON, MT;YAMADA, N
研究了连续皮下输注溶媒、SKF 38393（多巴胺D1受体激动剂）、（+）-4-丙基-9-羟基萘恶嗪（PHNO，多巴胺D2受体激动剂）或D1和D2受体激动剂336 h对大鼠自发活动的影响。在药物处理之前和期间，将大鼠保持在恒定的光照条件下，连续黑暗（黑暗：黑暗）或连续光照（光照：光照），以确定自由运行的昼夜节律对药物反应的影响。D2受体激动剂最初增加运动在大鼠保持在黑暗中：黑暗中主观夜间（最大运动期）和白天（最小运动期），但在大鼠保持在光：光在整个336小时的治疗没有影响。D2受体激动剂对保持在黑暗中的大鼠的运动刺激作用：在主观夜间（致敏）的治疗过程中，黑暗增加，但在大鼠的主观白天（耐受性）减少。D1受体激动剂SKF 38393本身没有影响，无论光照条件和治疗持续时间如何。然而，D1受体激动剂与D2受体激动剂在维持在光照下的大鼠中协同相互作用：光照取决于治疗持续时间。在黑暗条件下大鼠开始给药时也观察到协同效应：黑暗，但仅在主观白天。对受体激动剂协同作用的耐受性是治疗持续时间的函数，但仅在主观日内发生。D1受体激动剂在给药100 h后的大鼠主观夜间阻断了D2受体激动剂的作用，但在25或325 h后没有阻断。它的结论是，运动兴奋剂的D2受体激动剂的作用，行为D1/D2多巴胺受体的相互作用，和发展的敏化和耐受性的D2受体激动剂的运动效果是由内源性自由运行的昼夜节律，照明条件和治疗的持续时间。
The effects of continuous subcutaneous infusions of rats for 336 h with vehicle, SKF 38393 (a dopamine D1 receptor agonist), (+)-4-propyl-9-hydroxynaphthoxazine (PHNO, a dopamine D2 receptor agonist) or both D1 and D2 receptor agonists, on locomotor activity were investigated. Rats were maintained under constant lighting conditions, either continuous dark (dark:dark) or continuous light (light:light), before and during drug treatments in order to determine the influence of free-running circadian rhythms on drug responses. The D2 receptor agonist initially increased locomotion in rats kept under dark:dark during both subjective night (period of maximum locomotion) and day (period of minimum locomotion), but had no effect in rats maintained in light:light throughout the 336 h of treatment. The motor stimulant effects of the D2 receptor agonist on rats kept in dark:dark increased during the course of treatment during subjective night (sensitization), but decreased during the rats' subjective day (tolerance). The D1 receptor agonist, SKF 38393, had no effect on its own regardless of the lighting conditions and the duration of treatment. However, the D1 receptor agonist interacted synergistically with the D2 receptor agonist in rats maintained under light:light, depending on the duration of treatment. Synergistic effects were also observed on initiation of treatment in rats under dark:dark but only during subjective day. Tolerance to the synergistic effects of the receptor agonists occurred as a function of treatment duration, but only during subjective day. The D1 receptor agonist blocked the effects of the D2 receptor agonist during the rats' subjective night after 100 h of treatment, but not after 25 or 325 h. It is concluded that the motor stimulant effects of a D2 receptor agonist, behavioural D1/D2 dopamine receptor interactions, and the development of sensitization and tolerance to the locomotor effects of a D2 receptor agonist are determined by endogenous free-running circadian rhythms, lighting conditions and duration of treatment.