Berglund L A, Simpkins J W
Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville.
Neuroendocrinology. 1988 Oct;48(4):394-400. doi: 10.1159/000125040.
We have previously observed that gonadal steroid treatments, which stimulate a proestrous-like LH surge is ovariectomized rats, cause a marked reduction in the responsiveness to opiates of a variety of CNS processes. The present study was undertaken to determine if a similar decline in opiate responses is associated with the endogenous steroid-induced LH surge on the afternoon of proestrous. Rats were evaluated for thermic, nociceptive, behavioral and LH secretory responses to morphine sulfate on diestrous I afternoon (DiPM) and proestrous morning (ProAM), times at which LH secretion is low, as well as on proestrous afternoon (ProPM) during the preovulatory LH surge. While on DiPM and ProAM, morphine caused a 33-45% reduction in serum LH levels at doses as low as 5 mg/kg b.w., in ProPM rats doses as high as 10 mg/kg did not affect LH secretion. Similarly, ProAM rats showed a prompt and sustained analgesic response to morphine, but ProPM rats showed a delayed response of shorter duration. DiPM rats showed an acute response intermediate to that of ProAM and ProPM animals. While DiPM and proAM rats exhibited the expected hypothermic response to a high dose of morphine (15 mg/kg), ProPM rats showed no decline in core body temperature, but exhibited a delayed hyperthermic response to the opiate. DiPM and ProAM rats showed a dose-dependent decline in locomotor behavior in response to morphine. In contrast, ProPM rats, which exhibited a significantly elevated basal locomotor activity, failed to show a reduction in locomotion after morphine treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
我们之前观察到,性腺类固醇治疗可刺激去卵巢大鼠出现类似发情前期的促黄体生成素(LH)激增,且会导致多种中枢神经系统过程对阿片类药物的反应性显著降低。本研究旨在确定发情前期下午内源性类固醇诱导的LH激增是否伴有类似的阿片类药物反应下降。对大鼠在动情间期I下午(DiPM)和发情前期上午(ProAM)(此时LH分泌较低)以及排卵前LH激增期间的发情前期下午(ProPM)进行评估,观察其对硫酸吗啡的体温、伤害性感受、行为及LH分泌反应。在DiPM和ProAM时,低至5mg/kg体重的吗啡剂量可使血清LH水平降低33 - 45%,而在ProPM大鼠中,高达10mg/kg的剂量对LH分泌无影响。同样,ProAM大鼠对吗啡表现出迅速且持续的镇痛反应,而ProPM大鼠的反应延迟且持续时间较短。DiPM大鼠的急性反应介于ProAM和ProPM动物之间。虽然DiPM和ProAM大鼠对高剂量吗啡(15mg/kg)表现出预期的体温降低反应,但ProPM大鼠的核心体温未下降,而是对阿片类药物表现出延迟的体温升高反应。DiPM和ProAM大鼠对吗啡的运动行为呈剂量依赖性下降。相比之下,基础运动活动显著升高的ProPM大鼠在吗啡治疗后运动未减少。(摘要截短至250字)