Michaels Clifford C, Holtzman Stephen G
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Pharmacol Biochem Behav. 2007 Apr;86(4):784-96. doi: 10.1016/j.pbb.2007.03.007. Epub 2007 Mar 28.
Early-life stress has been identified as a risk factor in the development of a host of disorders, including substance abuse; however the link between early postnatal stress and changes in measures of reward has not been thoroughly researched. The current study had two main objectives: 1) to determine the impact of maternal separation (an animal model of early-life stress) on the consumption of 10% and 2.5% sucrose solutions by Long-Evans rat dams and male and female offspring, and 2) to determine the effect of the opioid antagonist naltrexone (0.1-3.0 mg/kg) on drinking by each of those groups. Dam-pup separations occurred for varying lengths of time during the first two postnatal weeks. In Experiment 1, a two-bottle choice test (sucrose solution vs. water) was administered across five days to both nonhandled (NH) and maternally-separated (MS) offspring as adults and to dams 2-4 weeks post-weaning. In Experiment 2, naltrexone was administered prior to two-bottle choice tests. MS males and the dams of MS litters exhibited increased intake of total fluid and sucrose solutions, whereas results from females were less consistent. Naltrexone elicited a greater decrease in fluid intake and sucrose intake in male MS offspring compared to male NH offspring. These results indicate that early postnatal stress alters both sucrose consumption, a non-drug measure of reward, and apparently the brain opioid systems that mediate naltrexone-induced drinking suppression.
早年生活应激已被确定为包括药物滥用在内的一系列疾病发展的风险因素;然而,出生后早期应激与奖赏指标变化之间的联系尚未得到充分研究。当前的研究有两个主要目标:1)确定母体分离(早年生活应激的一种动物模型)对Long-Evans大鼠母鼠以及雄性和雌性后代摄入10%和2.5%蔗糖溶液的影响,2)确定阿片类拮抗剂纳曲酮(0.1 - 3.0毫克/千克)对这些组中每组饮水的影响。在出生后的前两周内,母鼠与幼崽分离的时间长短各不相同。在实验1中,对成年时未处理(NH)和经母体分离(MS)的后代以及断奶后2 - 4周的母鼠进行了为期五天的双瓶选择测试(蔗糖溶液与水)。在实验2中,在双瓶选择测试前给予纳曲酮。MS雄性后代以及MS窝的母鼠表现出总液体和蔗糖溶液摄入量增加,而雌性的结果则不太一致。与雄性NH后代相比,纳曲酮使雄性MS后代的液体摄入量和蔗糖摄入量有更大幅度的减少。这些结果表明,出生后早期应激会改变蔗糖消耗(一种非药物奖赏指标),并且显然会改变介导纳曲酮诱导的饮水抑制的脑阿片系统。