Raftogianni A, Stamatakis A, Diamantopoulou A, Kollia A-M, Stylianopoulou F
Lab of Biology-Biochemistry, Faculty of Nursing, School of Health Sciences, University of Athens, 11527 Athens, Greece.
Lab of Biology-Biochemistry, Faculty of Nursing, School of Health Sciences, University of Athens, 11527 Athens, Greece.
Neuroscience. 2014 Jun 6;269:11-20. doi: 10.1016/j.neuroscience.2014.03.035. Epub 2014 Mar 27.
The mesolimbic/mesocortical dopaminergic pathway plays a pivotal role in the reward system. During the neonatal period the mother is the main source of rewarding stimuli. We have developed an experimental model in which rat pups learn a T-maze during the neonatal period (postnatal day (PND) 10-13) using contact with the mother as the reward. One group of animals is allowed contact with the mother (receipt of expected reward, RER) while the other was denied (denial of expected reward, DER). We determined the effects of these two early experiences in the prefrontal cortex (PFC) and the nucleus accumbens (nAc), the levels of dopamine (DA) and its metabolites [3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] by high-performance liquid chromatography and those of D1 and D2 receptors by autoradiographic in vitro binding both on PND 13 and in adulthood. On PND13, 2h after the end of training, the RER experience resulted in higher DA, HVA and D1 receptor levels in the nAc, while the DER in lower DA and its metabolites (DOPAC and HVA) in the PFC. These results could be related to the reward the RER pups received through the contact with their mother. The RER and DER early experience had long-term sex-dependent effects: The RER-induced activation of the dopaminergic system in the nAc was also evident in adult female rats. In contrast, adult DER males, similar to PND13 animals, had reduced dopamine in the PFC. Our results document that early experiences, a key determinant of adult brain function, affect the dopaminergic system which is disturbed in many psychiatric diseases.
中脑边缘/中脑皮质多巴胺能通路在奖赏系统中起关键作用。在新生儿期，母亲是奖赏性刺激的主要来源。我们开发了一种实验模型，其中新生大鼠幼崽在新生儿期（出生后第10 - 13天）通过与母亲接触作为奖赏来学习T迷宫。一组动物被允许与母亲接触（接受预期奖赏，RER），而另一组则被剥夺（剥夺预期奖赏，DER）。我们通过高效液相色谱法测定了这两种早期经历对前额叶皮质（PFC）和伏隔核（nAc）中多巴胺（DA）及其代谢产物[3,4 - 二羟基苯乙酸（DOPAC）和高香草酸（HVA）]水平的影响，并通过体外放射自显影结合法测定了出生后第13天和成年期D1和D2受体的水平。在出生后第13天，训练结束后2小时，RER经历导致nAc中DA、HVA和D1受体水平升高，而DER导致PFC中DA及其代谢产物（DOPAC和HVA）水平降低。这些结果可能与RER幼崽通过与母亲接触获得的奖赏有关。RER和DER早期经历具有长期的性别依赖性影响：RER诱导的nAc多巴胺能系统激活在成年雌性大鼠中也很明显。相比之下，成年DER雄性大鼠与出生后第13天的动物相似，PFC中的多巴胺减少。我们的结果表明，早期经历作为成年脑功能的关键决定因素，会影响多巴胺能系统，而该系统在许多精神疾病中受到干扰。
