Carvalho A F, Reyes B A S, Ramalhosa F, Sousa N, Van Bockstaele E J
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, 4710-057, Braga, Portugal.
ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
Brain Struct Funct. 2016 Jan;221(1):407-19. doi: 10.1007/s00429-014-0914-6. Epub 2014 Oct 28.
Recent studies demonstrate a differential trajectory for cannabinoid receptor expression in cortical and sub-cortical brain areas across postnatal development. In the present study, we sought to investigate whether chronic systemic exposure to a synthetic cannabinoid receptor agonist causes morphological changes in the structure of dendrites and dendritic spines in adolescent and adult pyramidal neurons in the medial prefrontal cortex (mPFC) and medium spiny neurons (MSN) in the nucleus accumbens (Acb). Following systemic administration of WIN 55,212-2 in adolescent (PN 37-40) and adult (P55-60) male rats, the neuronal architecture of pyramidal neurons and MSN was assessed using Golgi-Cox staining. While no structural changes were observed in WIN 55,212-2-treated adolescent subjects compared to control, exposure to WIN 55,212-2 significantly increased dendritic length, spine density and the number of dendritic branches in pyramidal neurons in the mPFC of adult subjects when compared to control and adolescent subjects. In the Acb, WIN 55,212-2 exposure significantly decreased dendritic length and number of branches in adult rat subjects while no changes were observed in the adolescent groups. In contrast, spine density was significantly decreased in both the adult and adolescent groups in the Acb. To determine whether regional developmental morphological changes translated into behavioral differences, WIN 55,212-2-induced aversion was evaluated in both groups using a conditioned place preference paradigm. In adult rats, WIN 55,212-2 administration readily induced conditioned place aversion as previously described. In contrast, adolescent rats did not exhibit aversion following WIN 55,212-2 exposure in the behavioral paradigm. The present results show that synthetic cannabinoid administration differentially impacts cortical and sub-cortical neuronal morphology in adult compared to adolescent subjects. Such differences may underlie the disparate development effects of cannabinoids on behavior.
近期研究表明，在出生后发育过程中，大麻素受体在大脑皮质和皮质下区域的表达轨迹存在差异。在本研究中，我们试图探究长期全身暴露于合成大麻素受体激动剂是否会导致内侧前额叶皮质（mPFC）中青少年和成年锥体神经元以及伏隔核（Acb）中中等棘状神经元（MSN）的树突和树突棘结构发生形态变化。在青少年（出生后第37 - 40天）和成年（出生后第55 - 60天）雄性大鼠全身给予WIN 55,212 - 2后，使用高尔基-考克斯染色法评估锥体神经元和MSN的神经元结构。与对照组相比，WIN 55,212 - 2处理的青少年组未观察到结构变化，但与对照组和青少年组相比，成年组mPFC中的锥体神经元在暴露于WIN 55,212 - 2后，树突长度、棘密度和树突分支数量显著增加。在Acb中，WIN 55,212 - 2暴露显著降低了成年大鼠的树突长度和分支数量，而青少年组未观察到变化。相比之下，Acb中成年组和青少年组的棘密度均显著降低。为了确定区域发育形态变化是否转化为行为差异，在两组中使用条件性位置偏好范式评估WIN 55,212 - 2诱导的厌恶。在成年大鼠中，WIN 55,212 - 2给药如前所述很容易诱导条件性位置厌恶。相比之下，在行为范式中，青少年大鼠在WIN 55,212 - 2暴露后未表现出厌恶。目前的结果表明，与青少年相比，合成大麻素给药对成年皮质和皮质下神经元形态的影响存在差异。这些差异可能是大麻素对行为产生不同发育影响的基础。
