Fuentes Silvia, Carrasco Javier, Hatto Abigail, Navarro Juan, Armario Antonio, Monsonet Manel, Ortiz Jordi, Nadal Roser
Institut de Neurociències, Universitat Autònoma de Barcelona, Barcelona, Spain.
Psychobiology Unit (School of Psychology), Universitat Autònoma de Barcelona, Barcelona, Spain.
PLoS One. 2018 Jan 11;13(1):e0190044. doi: 10.1371/journal.pone.0190044. eCollection 2018.
Early life stress (ELS) induces long-term effects in later functioning and interacts with further exposure to other stressors in adulthood to shape our responsiveness to reward-related cues. The attribution of incentive salience to food-related cues may be modulated by previous and current exposures to stressors in a sex-dependent manner. We hypothesized from human data that exposure to a traumatic (severe) adult stressor will decrease the attribution of incentive salience to reward-associated cues, especially in females, because these effects are modulated by previous ELS. To study these factors in Long-Evans rats, we used as an ELS model of restriction of nesting material and concurrently evaluated maternal care. In adulthood, the offspring of both sexes were exposed to acute immobilization (IMO), and several days after, a Pavlovian conditioning procedure was used to assess the incentive salience of food-related cues. Some rats developed more attraction to the cue predictive of reward (sign-tracking) and others were attracted to the location of the reward itself, the food-magazine (goal-tracking). Several dopaminergic markers were evaluated by in situ hybridization. The results showed that ELS increased maternal care and decreased body weight gain (only in females). Regarding incentive salience, in absolute control animals, females presented slightly greater sign-tracking behavior than males. Non-ELS male rats exposed to IMO showed a bias towards goal-tracking, whereas in females, IMO produced a bias towards sign-tracking. Animals of both sexes not exposed to IMO displayed an intermediate phenotype. ELS in IMO-treated females was able to reduce sign-tracking and decrease tyrosine hydroxylase expression in the ventral tegmental area and dopamine D1 receptor expression in the accumbens shell. Although the predicted greater decrease in females in sign-tracking after IMO exposure was not corroborated by the data, the results highlight the idea that sex is an important factor in the study of the long-term impact of early and adult stressors.
早期生活应激(ELS)会对后期功能产生长期影响,并与成年后进一步暴露于其他应激源相互作用,从而塑造我们对奖励相关线索的反应。对与食物相关线索的动机显著性归因可能会受到先前和当前应激源暴露的性别依赖性调节。基于人类数据我们推测,暴露于创伤性(严重)成年应激源会降低对奖励相关线索的动机显著性归因,尤其是在女性中,因为这些影响会受到先前ELS的调节。为了在长 Evans 大鼠中研究这些因素,我们使用限制筑巢材料作为 ELS 模型,并同时评估母性关怀。成年后,两性后代都接受急性固定(IMO),几天后,使用经典条件反射程序来评估与食物相关线索的动机显著性。一些大鼠对预测奖励的线索产生了更多吸引力(信号追踪),而另一些则被奖励本身的位置,即食物槽(目标追踪)所吸引。通过原位杂交评估了几种多巴胺能标记物。结果表明,ELS 增加了母性关怀并降低了体重增加(仅在雌性中)。关于动机显著性,在绝对对照动物中,雌性表现出比雄性稍大的信号追踪行为。未暴露于 ELS 的雄性大鼠在接受 IMO 后表现出偏向目标追踪的倾向,而在雌性中,IMO 导致偏向信号追踪的倾向。未接受 IMO 的两性动物表现出中间表型。接受 IMO 处理的雌性大鼠中的 ELS 能够减少信号追踪,并降低腹侧被盖区酪氨酸羟化酶的表达以及伏隔核壳中多巴胺 D1 受体的表达。尽管数据并未证实预测的 IMO 暴露后雌性信号追踪减少幅度更大,但结果突出了性别是研究早期和成年应激源长期影响的重要因素这一观点。