Ceci Chiara, Mela Virginia, Macrì Simone, Marco Eva M, Viveros Maria-Paz, Laviola Giovanni
Section of Behavioral Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Rome, Italy.
Psychopharmacology (Berl). 2014 May;231(10):2131-44. doi: 10.1007/s00213-013-3367-3. Epub 2013 Dec 6.
The central endocannabinoid system (eCB system) sustains the activity of the hypothalamus-pituitary-adrenal (HPA) axis in mediating individual emotional responses. Deviation in maturational trajectories of these two physiological systems, may persistently adjust individual behavioral phenotype.
We investigated, in outbred CD1 male mice, whether exposure to prenatal stress may influence short- and long-term emotional and neurochemical responses to a pharmacological stimulation of the eCB system during adolescence.
To mimic prenatal stress, pregnant mice were supplemented with corticosterone in the drinking water (33.3 mg/l); their adolescent male offspring received daily injections of the fatty acid amide hydrolase inhibitor, URB597 (0.4 mg/kg), in order to enhance eCB signaling. Mice were then tested for: locomotor activity during adolescence and locomotor activity, anxiogenic, and anhedonic profiles in adulthood. We analyzed the expression of CB1 receptors (CB1Rs) in prefrontal cortex, hippocampus, striatum, and cerebellum in adulthood.
Corticosterone administration (PC group) resulted, in adolescence, in a reduction in body weight and locomotion, while in adulthood, in increased anxiety-related behavior and reduced CB1Rs expression in cerebellum. URB597 exposure reduced locomotor activity and increased anhedonia in adulthood. CB1Rs were up-regulated in striatum and hippocampus and down-regulated in the cerebellum. PC-URB597 mice failed to show reductions in locomotion; exhibited increased risk assessment behavior; and showed reduced CB1Rs expression within the prefrontal cortex.
Present results provide support to the hypothesis that precocious manipulations mapping onto the HPA axis and eCB system may persistently adjust individual emotional responses and eCB system plasticity.
中枢内源性大麻素系统（eCB系统）在介导个体情绪反应时维持下丘脑 - 垂体 - 肾上腺（HPA）轴的活性。这两个生理系统成熟轨迹的偏差可能会持续调整个体行为表型。
我们在远交系CD1雄性小鼠中研究了产前应激暴露是否会影响青春期对eCB系统药理刺激的短期和长期情绪及神经化学反应。
为模拟产前应激，给怀孕小鼠的饮用水中添加皮质酮（33.3毫克/升）；它们的青春期雄性后代每天注射脂肪酸酰胺水解酶抑制剂URB597（0.4毫克/千克），以增强eCB信号传导。然后对小鼠进行以下测试：青春期的运动活动以及成年后的运动活动、焦虑样和快感缺失特征。我们分析了成年小鼠前额叶皮质、海马体、纹状体和小脑中CB1受体（CB1Rs）的表达。
给予皮质酮（PC组）在青春期导致体重和运动减少，而在成年期导致焦虑相关行为增加以及小脑中CB1Rs表达减少。暴露于URB597会降低成年小鼠的运动活动并增加快感缺失。CB1Rs在纹状体和海马体中上调，在小脑中下调。PC - URB597组小鼠的运动没有减少；表现出风险评估行为增加；并且前额叶皮质内的CB1Rs表达降低。
目前的结果支持以下假设，即映射到HPA轴和eCB系统上的早熟操作可能会持续调整个体情绪反应和eCB系统可塑性。
