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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Maternal exposure to low doses of delta9-tetrahydrocannabinol facilitates morphine-induced place conditioning in adult male offspring.
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Maternal exposure to low doses of delta9-tetrahydrocannabinol facilitates morphine-induced place conditioning in adult male offspring.

机译：孕妇暴露于低剂量的delta9-tetrahydrocannabinol可促进成年雄性后代中吗啡诱导的位置调节。

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摘要

The possible existence of an increased susceptibility to the reinforcing properties of morphine was analyzed in male and female rats born from mothers exposed to delta9-tetrahydrocannabinol (THC, 1, 5, or 20 mg/kg) during gestation and lactation. Maternal exposure to low doses of THC (1 and 5 mg/kg), relevant for human consumption, resulted in an increased response to the reinforcing effects of a moderate dose of morphine (350 microg/kg), as measured in the place-preference conditioning paradigm (CPP) in the adult male offspring. These animals also displayed an enhanced exploratory behavior in the defensive withdrawal test. However, only females born from mothers exposed to THC 1 mg/kg exhibited a small increment in the place conditioning induced by morphine. The possible implication of the hypothalamo-pituitary-adrenal axis (HPA) was analyzed by monitoring plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone in basal and moderate-stress conditions (after the end of the CPP test). Female offspring perinatally exposed to THC (1 or 5 mg/kg) displayed high basal levels of corticosterone and a blunted adrenal response to the HPA-activating effects of the CPP test. However, male offspring born from mothers exposed to THC (1 or 5 mg/kg) displayed the opposite pattern: normal to low basal levels of corticosterone, and a sharp adrenal response to the CPP challenge. The present study reveals that maternal exposure to low doses of THC results in an increased sensitivity to the reinforcing effects of morphine in the adult male offspring, and in sexually dimorphic behavioral and endocrine alterations in the adaptative responses to stressors such as novelty or place-preference testing. These results support the growing evidence of the importance of monitoring the long-term consequences of maternal consumption of cannabis derivatives.
机译：分析了在妊娠和哺乳期间暴露于delta9-四氢大麻酚（THC，1、5或20 mg / kg）的母亲所生的雄性和雌性大鼠中对吗啡增强特性的敏感性增加的可能存在。孕产妇暴露于与人类食用有关的低剂量四氢大麻酚（1和5 mg / kg）中，导致对中等剂量吗啡（350 microg / kg）的增强作用的反应增强，如在场所偏爱中所测成年男性后代中的条件范式（CPP）。这些动物在防御性撤退测试中还表现出增强的探索行为。但是，只有母亲暴露于THC 1 mg / kg的女性所产的雌性吗啡诱导的位置调节有少量增加。通过监测在基础和中等压力条件下（CPP测试结束后）的促肾上腺皮质激素（ACTH）和皮质酮的血浆水平来分析下丘脑-垂体-肾上腺轴（HPA）的可能含义。围产期暴露于THC（1或5 mg / kg）的雌性后代对CPP测试的HPA激活作用显示出较高的基础皮质酮水平，肾上腺反应迟钝。但是，母亲暴露于四氢大麻酚（1或5 mg / kg）后出生的雄性后代表现出相反的模式：正常至较低的基础皮质酮水平，以及对CPP刺激的强烈肾上腺反应。本研究表明，母体暴露于低剂量的四氢大麻酚会导致对成年雄性后代吗啡增强作用的敏感性增加，并导致对新奇或场所偏好等应激源的适应性反应中的双态性行为和内分泌改变测试。这些结果支持越来越多的证据表明，监测孕产妇食用大麻衍生物的长期后果的重要性。

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