Roberts Benjamin Z, O'Connor Molly A, Kenton Johnny A, Barnes Samuel A, Young Jared W
Department of Psychiatry, UC San Diego School of Medicine, University of California, San Diego, La Jolla, CA, 92093-0804, USA.
Research Service, VA San Diego Healthcare System, San Diego, USA.
Psychopharmacology (Berl). 2023 Nov;240(11):2303-2315. doi: 10.1007/s00213-023-06337-3. Epub 2023 Feb 18.
Seasonal birth patterns consistently implicate winter gestation as a risk factor for several psychiatric conditions. We recently demonstrated that short-active (SA; 19:5 light:dark)-i.e., "winter-like"-photoperiod exposure across gestation and early life (E0-P28) induces psychiatrically relevant behavioral abnormalities in adult mice, including reduced immobility in the forced swim test (FST) and effortful amotivation. It is unknown, however, whether these effects were driven primarily by prenatal or postnatal mechanisms, and whether perinatal SA photoperiod would similarly reduce effort expenditure in a task relevant to everyday decision-making.
We first tested male and female mice exposed to either gestational (E0-P0) or postnatal (E0-P28) SA photoperiod in the FST to determine whether the previously observed alteration was driven primarily by prenatal versus postnatal photoperiod. We then assessed whether SA gestational photoperiod reduces effortful choice behavior in the cross-species effort-based decision-making task (EBDMT) and whether any such deficit could be remediated by d-amphetamine (0.1 and 0.3 mg/kg, i.p.).
Mice exposed to prenatal, but not postnatal, SA photoperiod exhibited reduced FST immobility relative to controls and also demonstrated condition-dependently reduced preference for high-effort/high-reward versus low-effort/low-reward contingencies in the EBDMT. This effortful choice deficit was normalized by 0.1 mg/kg amphetamine.
These data: (1) suggest a greater contribution of gestational versus postnatal light conditions to the behavioral effects of perinatal SA photoperiod; and (2) implicate altered dopamine signaling in the behavioral phenotype of the SA-born mouse and possibly in the etiology of winter gestation-associated cases of psychiatric disease.
季节性出生模式一直表明冬季妊娠是多种精神疾病的危险因素。我们最近证明,在整个妊娠期和生命早期(E0 - P28)暴露于短光照(SA;19:5光照:黑暗)——即“类似冬季”的光周期——会在成年小鼠中诱发与精神相关的行为异常,包括在强迫游泳试验(FST)中不动时间减少以及努力缺乏动力。然而,尚不清楚这些影响主要是由产前还是产后机制驱动的,以及围产期SA光周期是否会同样减少与日常决策相关任务中的努力消耗。
我们首先在FST中测试暴露于妊娠期(E0 - P0)或产后(E0 - P28)SA光周期的雄性和雌性小鼠,以确定先前观察到的改变主要是由产前还是产后光周期驱动的。然后,我们评估SA妊娠期光周期是否会减少跨物种基于努力的决策任务(EBDMT)中的努力选择行为,以及这种缺陷是否可以通过d - 苯丙胺(0.1和0.3 mg/kg,腹腔注射)得到改善。
与对照组相比,暴露于产前而非产后SA光周期的小鼠在FST中的不动时间减少,并且在EBDMT中也表现出根据条件对高努力/高回报与低努力/低回报意外情况的偏好降低。这种努力选择缺陷通过0.1 mg/kg苯丙胺恢复正常。
这些数据:(1)表明妊娠期而非产后光照条件对围产期SA光周期的行为影响贡献更大;(2)提示SA出生小鼠行为表型中多巴胺信号改变,可能与冬季妊娠相关精神疾病病例的病因有关。