Neurostress UPRES EA 4347 and CNRS UMR 8576, Université Lille Nord de France, University of Lille 1, 59655, Villeneuve d'Ascq, France.
Psychopharmacology (Berl). 2011 Mar;214(1):197-208. doi: 10.1007/s00213-009-1765-3. Epub 2010 Jan 27.
In rats, prenatal restraint stress (PRS) induces persistent behavioral and neurobiological alterations leading to a greater consumption of psychostimulants during adulthood. However, little is known about alcohol vulnerability in this animal model.
We examined in adolescent and adult male Sprague Dawley rats the long-lasting impact of PRS exposure on alcohol consumption.
PRS rats were subjected to a prenatal stress (three daily 45-min sessions of restraint stress to the mothers during the last 10 days of pregnancy). Alcohol preference was assessed in a two-bottle choice paradigm (alcohol 2.5%, 5%, or 10% versus water), in both naïve adolescent rats and adult rats previously exposed to a chronic alcohol treatment. Behavioral indices associated with incentive motivation for alcohol were investigated. Finally, plasma levels of transaminases (marker of hepatic damages) and ΔFosB levels in the nucleus accumbens (a potential molecular switch for addiction) were evaluated following the chronic alcohol exposure.
Alcohol preference was not affected by PRS. Contrary to our expectations, stressed and unstressed rats did not display signs of compulsive alcohol consumption. The consequences of the alcohol exposure on locomotor reactivity and on transaminase levels were more prominent in PRS group. Similarly, PRS potentiated alcohol-induced ΔFosB levels in the nucleus accumbens.
Our data suggest that negative events occurring in utero do not modulate alcohol preference in male rats but potentiate chronic alcohol-induced molecular neuroadaptation in the brain reward circuitry. Further studies are needed to determine whether the exacerbated ΔFosB upregulation in PRS rats could be extended to other reinforcing stimuli.
在大鼠中,产前束缚应激(PRS)会导致持久的行为和神经生物学改变,从而导致成年后对精神兴奋剂的消费增加。然而,关于这种动物模型中的酒精易感性知之甚少。
我们在青春期和成年雄性 Sprague Dawley 大鼠中检查了 PRS 暴露对酒精消费的长期影响。
PRS 大鼠接受产前应激(在妊娠最后 10 天每天对母亲进行三次 45 分钟的束缚应激)。在双瓶选择范式中评估酒精偏好(酒精 2.5%、5%或 10%与水),包括在未接触过慢性酒精处理的青春期大鼠和成年大鼠中。研究了与酒精激励动机相关的行为指标。最后,在慢性酒精暴露后评估了血浆转氨酶水平(肝损伤标志物)和伏隔核中的 ΔFosB 水平(成瘾的潜在分子开关)。
PRS 并未影响酒精偏好。与我们的预期相反,应激和非应激大鼠没有表现出强迫性饮酒的迹象。在 PRS 组中,酒精暴露对运动反应性和转氨酶水平的影响更为明显。同样,PRS 增强了酒精诱导的伏隔核中 ΔFosB 水平。
我们的数据表明,宫内发生的负面事件不会调节雄性大鼠对酒精的偏好,但会增强大脑奖励回路中慢性酒精诱导的分子神经适应。需要进一步的研究来确定 PRS 大鼠中增强的 ΔFosB 上调是否可以扩展到其他强化刺激。