大鼠出生后不同时期使用氟西汀对体质量和行为远期影响的初步研究

Long-term influence of fluoxetine exposure at different neonate period on the body weight and behavior of rats

目的 探讨大鼠出生后不同时期使用氟西汀对其体质量和行为的远期影响.方法 随机选择雄性SPrague-Dawley大鼠,在其出生后1～7 d、8～21 d分别皮内注射氟西汀（浓度2 g/L,注射剂量5 ml/kg体质量）（F1组,22只;F2组,20只）和生理盐水（0.9%NaCl,注射剂量5 ml/kg体质量）（S1组,20只;S2组,19只）,并追踪观察4组大鼠体质量;大鼠成年后（出生后第90天）进行行为学检测,包括旷场实验、高架十字迷宫、新奇抑制摄食和强迫游泳实验.结果 （1）F1组大鼠体质量的增加延缓,出生后第25天,F1组体质量[（35.5±3.4）g]于S1组[（43.0±3.9）g],至出生后第90天,F1组体质量[（190.7±12.1）g]均小于S1组[（208.0±13.5）g]和F2组[（218.3±14.6）g]（两样本t检验,P＜0.05）.（2）幼鼠早期使用氟西汀,成年后探索性行为减少,F1组旷场行为总行程[（18.9±2.3）m]明显小于S1组[（38.9±8.1）m],F2组[（33.3±6.2）m]于S2组[（43.7±6.2）m];高架十字迷宫总穿臂次数F1组[（13.8±3.2）次]少于S1组[（37.6±6.3）次],F2组[（32.3±7.1）次]少于S2组[（57±7.3）次]（两样本t检验,P＜0.05）;焦虑抑郁相关行为增加,新奇抑制摄食潜伏期F1组[（432.2±45.4）s]长于S1组[（167.7±20.3）s],F2组[（270.2±27.2）s]长于S2组[（185.3±19.2）s];强迫游泳静止不动时间百分比F1组[（41.2±3.2）%]长于S1组[（26.5±2.3）%],F2组[（35.1±3.6）%]长于S2组[（27.8±2.5）%]（两样本t检验,P＜0.05）;且F1组大鼠的异常行为重于F2组（两样本t检验,P＜0.05）.结论 幼鼠出生后早期使用氟西汀可导致大鼠体质量增加延缓,成年后出现焦虑抑郁行为,使用氟西汀越早风险越大.

Objective To evaluate the long-term influence of fluoxetine exposure at different neonate period on the body weight and behavior in rats. Methods Male SPrague-Dawley rats were randomized to be treated with fluoxetine （concentration： 2 g/L, 5 ml/kg） （F1 ：n =22,F2：n =20）or saline （0. 9% NaCl, 5 ml/kg） （S1 ：n =20,S2：n = 19） on days 1 -7 or days 8 -21 after birth. The body weights of rats in all 4 groups were trailed. Ethological tests, including open field test, elevated-plus maze, noveltysuppressed feeding test and forced swim test, were performed in the adult rats （90 days after birth）. Results （ 1 ） Weight gain was delayed to 25 days after birth in F1 group, and was lower [ （ 35.5 ± 3.4 ） g ] in comparison to group S1 [ （43. 0 ± 3.9） g], and was [ （190. 7 ± 12. 1 ） g] lower than that in group S1[ （208.0±13.5） g] and group F2 [218.3 ± 14.6） g] on days 90 （P 〈0.05）. （2） Early fluoxetine exposure in neonate led to reduced exploratory behavior in adult rats. The total distance traveled in open field was significantly shorter in group F1 [ （ 18.9 ± 2. 3） m] than in group S1 [ （38. 9 ± 8. 1 ） m], and shorter in group F2 [ （33. 3 ± 6. 2） m ] than in group S2 [ （43.7 ± 6. 2 ） m ]. The total entries in elevated plus-maze was fewer in group F1 （ 13. 8 ± 3.2） than in group S1 （ 37. 6 ± 6. 3 ）, and fewer in group F2 （ 32. 3 ± 7. 1 ）than in group S2 （57 ± 7.3 ） （ P 〈 0. 05 ）. Depression anxiety behavior increased in adult rats with neonatal fluoxetine exposure, the latency in novelty-suppressed feeding test was longer in group F1 [ （432. 2 ±45.4）s] than in group S1[ （167.7 ±20.3） s], and longer in group F2[ （270. 2 ±27.2） s] than in group S2[ （ 185.3 ± 19. 2） s], the percentage observations of immobility in forced swim test was higher in group F1[ （41.2 ± 3. 2 ）% ] than in group S1 [ （26. 5 ± 2. 3 ）% ], and in group F2 [ （35. 1 ± 3.6 ）% ] than in group S2 [ （ 27. 8± 2. 5 ） % ] （ P 〈 0. 05 ） . Abnormal behavior was severer in group F1 than in group F2（P 〈0. 05）. Conclusions Early exposure to fluoxetine after birth may result in slower weight gain and depression anxiety behavior in adult rats, the earlier fluoxetine exposure, the higher risk.