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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Circadian rhythm-dependent development of melatonin effects and tolerance to PHNO in rats.
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Circadian rhythm-dependent development of melatonin effects and tolerance to PHNO in rats.

机译：昼夜节律依赖性褪黑激素作用的发展和对大鼠PHNO的耐受性。

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摘要

Male Sprague-Dawley rats were given 12 days of continuous infusions of (+)-4-propyl-9-hyroxynapthoxazine (PHNO, 5&mgr;g/h), a highly selective dopamine D(2) receptor agonist, via subcutaneous ALZET((R)) osmotic pumps. Motor stimulant effects (locomotion and rearing) were monitored throughout the treatment period, including after the animals were injected with 2-iodo-melatonin (0.5 mg/kg) on days 8-10 and 13 after initiation of PHNO infusions. The rats (maintained on 12 L:12 D cycle) developed tolerance to the motor stimulant effects of PHNO during the day, and behavioral sensitization to PHNO during the night. Arousing rats with a vehicle injection transiently blocked the daytime tolerance. A more sustained environmental noise without handling of animals, which had a stronger effect on increasing motor activity of control rats, reversed tolerance to sensitization. Therefore, graded levels of arousal produce graded increases in motor activity in rats otherwise tolerant to the effects of PHNO. Daytime tolerance to PHNO was reversed to sensitization by 2-iodo-melatonin. This effect was more than an additive effect of drug + injection procedure stress. The differential development of nocturnal sensitization and diurnal tolerance to PHNO effects on motor activity may depend upon circadian rhythms in melatonin release, as well as on state of arousal.
机译：通过皮下ALZET给雄性Sprague-Dawley大鼠连续12天连续输注高度选择性的多巴胺D（2）受体激动剂（+）-4-丙基-9-羟吗啡嗪（PHNO，5＆g / g / h）（（ R））渗透泵。在整个治疗期间，包括在开始PHNO输注后的第8-10天和第13天，对动物注射2-碘褪黑激素（0.5 mg / kg）后，均监测运动刺激作用（运动和饲养）。大鼠（维持12 L：12 D周期）在白天对PHNO的运动刺激作用产生耐受性，而在夜间对PHNO的行为敏感。用媒介物注射激怒大鼠暂时阻断了白天的耐受性。在不处理动物的情况下，环境噪声持续时间更长，对控制大鼠的运动活动具有更强的作用，从而逆转了对敏化的耐受性。因此，在其他情况下耐受PHNO作用的大鼠中，唤醒活动的分级水平会导致其运动活动的分级增加。白天对PHNO的耐受性被2-碘褪黑激素逆转为致敏作用。该效果远大于药物+注射程序压力的累加效果。夜间敏化和对PHNO对运动活动影响的昼夜耐受性的差异发展可能取决于褪黑激素释放的昼夜节律以及唤醒状态。

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