Lisboa Sabrina F S, Oliveira Paulo E, Costa Leandro C, Venâncio Emerson J, Moreira Estefânia G
Department of Physiological Sciences, State University of Londrina, Londrina, Brazil.
Pharmacology. 2007;80(1):49-56. doi: 10.1159/000103097. Epub 2007 May 23.
BACKGROUND/AIMS: Fluoxetine (FLX) has been widely prescribed for depression during pregnancy and/or lactation. Since serotonin is a neurotrophic factor, the use of FLX by mothers could disrupt brain development resulting in behavioral alterations in their progeny. This study evaluated the effects of developmental FLX exposure on anxiety, depression, aggressivity and pain sensitivity of male and female mice pups.
Swiss dams were treated daily, by gavage, with 7.5 mg/kg of FLX during pregnancy and lactation. Pups were submitted to open-field, forced swimming, elevated plus-maze, intruder-resident and hot plate tests at adolescence and adulthood.
In male pups, exposure to FLX decreased ambulation at postnatal day (PND) 40 and tended (p=0.07) to increase the latency to the first attack in the intruder-resident test at PND 70, suggesting decreased impulsivity. In female pups, FLX exposure increased immobility time in the forced swimming test at both PND 30 and 70, which is interpreted as depressive-like behavior. In conclusion, our results suggest that maternal exposure to FLX during pregnancy and lactation results in enduring behavioral alterations in male and female pups throughout life.
背景/目的：氟西汀（FLX）已被广泛用于孕期和/或哺乳期抑郁症的治疗。由于血清素是一种神经营养因子，母亲使用氟西汀可能会干扰大脑发育，导致其后代出现行为改变。本研究评估了发育过程中暴露于氟西汀对雄性和雌性小鼠幼崽焦虑、抑郁、攻击性和疼痛敏感性的影响。
瑞士母鼠在怀孕和哺乳期每天通过灌胃给予7.5mg/kg的氟西汀。幼崽在青春期和成年期接受旷场试验、强迫游泳试验、高架十字迷宫试验、入侵者-居住者试验和热板试验。
在雄性幼崽中，暴露于氟西汀会使出生后第40天（PND40）的活动减少，并在出生后第70天（PND70）的入侵者-居住者试验中倾向于（p=0.07）增加首次攻击的潜伏期，表明冲动性降低。在雌性幼崽中，暴露于氟西汀会使出生后第30天和第70天的强迫游泳试验中的不动时间增加，这被解释为类似抑郁的行为。总之，我们的结果表明，孕期和哺乳期母亲暴露于氟西汀会导致雄性和雌性幼崽终生出现持久的行为改变。
