Rubio P, Rodríguez de Fonseca F, Martín-Calderón J L, Del Arco I, Bartolomé S, Villanúa M A, Navarro M
Instituto Universitario de Drogodependencias (Departamento de Psicobiología, Facultad de Psicología), Universidad Complutense, Madrid, Spain.
Pharmacol Biochem Behav. 1998 Nov;61(3):229-38. doi: 10.1016/s0091-3057(98)00099-9.
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.
对妊娠和哺乳期暴露于δ9 - 四氢大麻酚（THC，1、5或20毫克/千克）的母鼠所生的雄性和雌性大鼠中，是否存在对吗啡强化特性易感性增加的情况进行了分析。母鼠暴露于与人类消费相关的低剂量THC（1和5毫克/千克），导致成年雄性后代在位置偏爱条件反射范式（CPP）中对中等剂量吗啡（350微克/千克）的强化作用反应增强。这些动物在防御性退缩试验中也表现出增强的探索行为。然而，只有出生于暴露于1毫克/千克THC的母鼠的雌性后代在吗啡诱导的位置条件反射中表现出小幅增加。通过监测基础和中等应激条件下（CPP试验结束后）促肾上腺皮质激素（ACTH）和皮质酮的血浆水平，分析了下丘脑 - 垂体 - 肾上腺轴（HPA）的可能影响。围产期暴露于THC（1或5毫克/千克）的雌性后代表现出高基础水平的皮质酮，并且对CPP试验的HPA激活作用的肾上腺反应减弱。然而，出生于暴露于THC（1或5毫克/千克）的母鼠的雄性后代表现出相反的模式：皮质酮基础水平正常至低水平，并且对CPP挑战有强烈的肾上腺反应。本研究表明，母鼠暴露于低剂量THC会导致成年雄性后代对吗啡强化作用的敏感性增加，并在对新奇或位置偏爱测试等应激源的适应性反应中出现性别差异的行为和内分泌改变。这些结果支持了越来越多的证据表明监测母体食用大麻衍生物的长期后果的重要性。
