Department of Biomedical Sciences, Section of Reproduction and Neuroscience, Tufts University, Cummings School of Veterinary Medicine, 200 Westboro Rd., North Grafton, MA 01536, United States.
Behav Brain Res. 2011 Mar 17;218(1):200-5. doi: 10.1016/j.bbr.2010.11.059. Epub 2010 Dec 5.
The use of narcotics by adolescent females is a growing problem, yet very little is known about the long-term consequences for either the user or her future offspring. In the current study, we utilized an animal model to examine the transgenerational consequences of opiate exposure occurring during this sensitive period. Female rats were exposed to increasing doses of morphine or its saline vehicle twice daily during adolescent development (postnatal days 30-40), after which they remained drug free. At 60 days of age, all females were mated and their adult offspring were tested for anxiety-like behavior and sensitivity to morphine. Specifically, offspring of adolescent morphine (MOR-F1)- or saline (SAL-F1)-exposed mothers were tested for acute locomotor responses in an open field, followed by testing of acute or chronic morphine analgesia on the hot plate. Open field testing indicated alterations in anxiety-like behavior in MOR-F1 female offspring, with effects dependent upon the stage of the estrus cycle. Hot plate testing revealed sex differences in baseline pain threshold and morphine sensitivity in all offspring, regardless of maternal exposure. However, when compared to their SAL-F1 counterparts, MOR-F1 male offspring demonstrated significantly increased sensitivity to the analgesic effects of acute morphine, and developed analgesic tolerance more rapidly following chronic morphine treatment. The findings indicate that prior opiate exposure during early adolescence in females produces sex-specific alterations of both emotionality and morphine sensitivity in their progeny.
青少年女性使用麻醉品是一个日益严重的问题，但对于使用者或她未来的后代，人们对此知之甚少。在目前的研究中，我们利用动物模型来研究在这个敏感时期发生的阿片类药物暴露对后代的长期影响。雌性大鼠在青春期发育期间（出生后第 30-40 天）每天两次接受递增剂量的吗啡或其生理盐水载体暴露，之后不再接触药物。在 60 天时，所有雌性大鼠都进行了交配，其成年后代接受了焦虑样行为和对吗啡敏感性的测试。具体来说，青春期吗啡（MOR-F1）或生理盐水（SAL-F1）暴露母亲的后代在开放场中接受急性运动反应测试，然后在热板上测试急性或慢性吗啡镇痛。开放场测试表明，MOR-F1 雌性后代的焦虑样行为发生了改变，这种影响取决于动情周期的阶段。热板测试显示，无论母体暴露如何，所有后代的基础疼痛阈值和吗啡敏感性都存在性别差异。然而，与 SAL-F1 对应物相比，MOR-F1 雄性后代对急性吗啡的镇痛效果表现出明显更高的敏感性，并且在慢性吗啡治疗后更快地发展出镇痛耐受。这些发现表明，女性在青春期早期接触阿片类药物会导致其后代的情感和吗啡敏感性出现特定的性别改变。
