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首页> 外文期刊>The European Journal of Neuroscience >Sexually dimorphic activation of the periaqueductal gray-rostral ventromedial medullary circuit during the development of tolerance to morphine in the rat.
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Sexually dimorphic activation of the periaqueductal gray-rostral ventromedial medullary circuit during the development of tolerance to morphine in the rat.

机译：在大鼠对吗啡的耐受性发展过程中，导水管周围灰色灰质腹侧延髓的性双态激活。

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The midbrain periaqueductal gray (PAG) and its descending projections to the rostral ventromedial medulla (RVM) provides an essential neural circuit for the antinociceptive effects of opiates, and has been implicated in the development of tolerance to morphine. Systemic morphine activates a greater proportion of PAG-RVM neurons in male vs female rats, and induces tolerance to a greater degree in males. The present studies tested the hypothesis that if the PAG-RVM pathway is essential for the development of tolerance, then: (i) morphine activation of the PAG-RVM pathway should decline as tolerance develops; and (ii) sex differences in the development of tolerance to morphine should be reflected as a greater decline in the activation of this pathway in males. These hypotheses were tested in male and female rats using behavioral testing (hot-plate) and immunohistochemistry to map the activation of the PAG-RVM pathway following repeated morphine administration (5 mg/kg; s.c.). In males, morphine potency decreased from 3.0 to 6.3 mg/kg, indicating tolerance, and this was paralleled by a steady decline in the percentage of PAG-RVM output neurons activated by morphine. In contrast, in females the shift in morphine potency was significantly attenuated (D(50) 6-8.3 mg/kg), and no significant difference in the activity of PAG-RVM output neurons was noted. These results demonstrate that the greater development of tolerance to morphine administration in male rats corresponds with a significant reduction in the activation of the PAG-RVM circuit and suggest a central role for the PAG in the development of tolerance to morphine.
机译：中脑导水管周围灰色（PAG）及其向下投影到延髓腹侧延髓（RVM）为鸦片的抗伤害感受作用提供了必不可少的神经回路，并且与吗啡耐受性的发展有关。系统性吗啡在雄性和雌性大鼠中激活更大比例的PAG-RVM神经元，并在雄性中诱导更大程度的耐受性。本研究检验了以下假设：如果PAG-RVM途径对耐受性的发展至关重要，则：（i）随着耐受性的发展，PAG-RVM途径的吗啡激活应下降; （ii）对吗啡的耐受性发展中的性别差异应反映为男性中该途径活化程度的更大下降。使用行为测试（热板）和免疫组织化学法在雄性和雌性大鼠中测试了这些假设，以绘制重复给予吗啡（5 mg / kg;皮下注射）后PAG-RVM途径的激活情况。在男性中，吗啡效价从3.0毫克/千克降低至6.3毫克/千克，表明具有耐受性，与此同时，吗啡激活的PAG-RVM输出神经元的百分比稳定下降。相比之下，在女性中，吗啡效价的变化显着减弱（D（50）6-8.3 mg / kg），并且未观察到PAG-RVM输出神经元活性的显着差异。这些结果表明，雄性大鼠对吗啡给药的耐受性的更大发展与PAG-RVM回路激活的显着降低相对应，并暗示了PAG在吗啡耐受性发展中的重要作用。

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