Department of Psychology, The University of Texas at El Paso, El Paso, TX, USA; Department of Psychology, California State University, San Bernardino, CA, USA.
Fishberg Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
J Affect Disord. 2019 Apr 15;249:347-356. doi: 10.1016/j.jad.2019.02.051. Epub 2019 Feb 19.
Epidemiological reports indicate that mood-related disorders are common in the adolescent population. The prevalence of juvenile major depressive disorder has resulted in a parallel increase in the prescription rates of fluoxetine (FLX) within this age group. Although such treatment can last for years, little is known about the enduring consequences of adolescent antidepressant exposure on memory-related performance.
We exposed separate groups of adolescent (postnatal day [PD] 35) male and female C57BL/6 mice to FLX (20 mg/kg) for 15 consecutive days (PD35-49). Three weeks after FLX exposure (PD70), we assessed learning and memory performance on a single-day training object novelty recognition test, or a spatial memory task on the Morris water maze (MWM).
We found that FLX pretreatment did not influence performance on either the object novelty recognition task or the MWM, 24 h after training. Conversely, 48 h post spatial-training on the MWM, FLX pretreated male mice spent significantly less time on the quadrant of the missing platform during a standard probe trial. No differences in MWM performance were observed in the adult female mice pretreated with FLX.
A limitation of this study is that normal adolescent mice (i.e., non-stressed) were evaluated for memory-related behavior three weeks after antidepressant exposure. Thus, it is possible that FLX pre-exposure in combination with animal models for the study of depression may yield different results.
Together, these results demonstrate enduring spatial memory-related deficiencies after pre-exposure to FLX during adolescence in male, but not female, C57BL/6 mice.
流行病学报告表明，情绪相关障碍在青少年人群中很常见。青少年重度抑郁症的患病率导致该年龄段氟西汀（FLX）的处方率也相应增加。尽管这种治疗可能持续多年，但人们对青少年抗抑郁药物暴露对与记忆相关的表现的持久后果知之甚少。
我们将单独的雄性和雌性 C57BL/6 幼鼠（出生后第 35 天）分别暴露于氟西汀（20mg/kg）中，连续 15 天（第 35-49 天）。在氟西汀暴露后 3 周（第 70 天），我们在单次训练日物体新颖性识别测试或 Morris 水迷宫（MWM）上的空间记忆任务上评估学习和记忆表现。
我们发现，氟西汀预处理不影响物体新颖性识别任务或 MWM 的表现，在训练后 24 小时。相反，在 MWM 空间训练后 48 小时，氟西汀预处理的雄性小鼠在标准探针试验中在缺失平台的象限上花费的时间明显减少。氟西汀预处理的成年雌性小鼠在 MWM 上的表现没有差异。
本研究的一个局限性是，在抗抑郁药物暴露后三周评估了正常青少年小鼠（即未受压力）的记忆相关行为。因此，氟西汀预先暴露结合抑郁研究的动物模型可能会产生不同的结果。
综上所述，这些结果表明，在雄性但不是雌性 C57BL/6 小鼠中，在青春期预先暴露于氟西汀后，会出现持久的空间记忆相关缺陷。
