Majcher-Maślanka Iwona, Solarz Anna, Wędzony Krzysztof, Chocyk Agnieszka
Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, 31-343 Kraków, Smętna Street 12, Poland.
Institute of Pharmacology, Polish Academy of Sciences, Laboratory of Pharmacology and Brain Biostructure, 31-343 Kraków, Smętna Street 12, Poland.
Int J Dev Neurosci. 2017 Apr;57:24-33. doi: 10.1016/j.ijdevneu.2017.01.001. Epub 2017 Jan 5.
During adolescence, many neural systems, including the dopamine system, undergo essential remodeling and maturation. It is well known that early-life stress (ELS) increases the risk for many psychopathologies during adolescence and adulthood. It is hypothesized that ELS interferes with the maturation of the dopamine system. There is a sex bias in the prevalence of stress-related mental disorders. Information regarding the effects of ELS on brain functioning in females is very limited. In the current study, maternal separation (MS) procedures were carried out to study the effects of ELS on dopamine system functioning in adolescent female rats. Our study showed that MS increased the density of tyrosine hydroxylase immunoreactive fibers in the prelimbic cortex (PLC) and nucleus accumbens (Acb). These changes were accompanied by a decrease in the level of D5 receptor mRNA and an increase in D2 receptor mRNA expression in the PLC of MS females. Conversely, D1 and D5 receptor mRNA levels were augmented in the caudate putamen (CPu), while the expression of the D3 dopamine receptor transcript was reduced in MS females. Additionally, in the Acb, MS elicited a decrease in D2 receptor mRNA expression. At the behavioral level, MS increased apomorphine-induced locomotion; however, it did not change locomotor responses to selective D1/D5 receptor agonist and attenuated D2/D3 receptor agonist-triggered locomotion. Moreover, MS decreased D1/D5 receptor agonist-induced grooming behavior. These results indicate that ELS disrupts dopamine receptor function in the PLC and basal ganglia during adolescence in females and may predispose them to psychopathologies during adolescence and adulthood.
在青春期，包括多巴胺系统在内的许多神经系统会经历重要的重塑和成熟过程。众所周知，早年生活应激（ELS）会增加青春期和成年期出现多种精神疾病的风险。据推测，ELS会干扰多巴胺系统的成熟。应激相关精神障碍的患病率存在性别差异。关于ELS对雌性大脑功能影响的信息非常有限。在本研究中，采用母婴分离（MS）程序来研究ELS对青春期雌性大鼠多巴胺系统功能的影响。我们的研究表明，MS增加了前边缘皮层（PLC）和伏隔核（Acb）中酪氨酸羟化酶免疫反应性纤维的密度。这些变化伴随着MS雌性大鼠PLC中D5受体mRNA水平的降低和D2受体mRNA表达的增加。相反，尾状壳核（CPu）中D1和D5受体mRNA水平升高，而MS雌性大鼠中D3多巴胺受体转录本的表达降低。此外，在Acb中，MS导致D2受体mRNA表达减少。在行为水平上，MS增加了阿扑吗啡诱导的运动；然而，它并没有改变对选择性D1/D5受体激动剂的运动反应，并减弱了D2/D3受体激动剂引发的运动。此外，MS减少了D1/D5受体激动剂诱导的梳理行为。这些结果表明，ELS在青春期会破坏雌性大鼠PLC和基底神经节中的多巴胺受体功能，并可能使它们在青春期和成年期易患精神疾病。
