Hauser K F, McLaughlin P J, Zagon I S
Department of Anatomy, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
J Comp Neurol. 1989 Mar 1;281(1):13-22. doi: 10.1002/cne.902810103.
The role of endogenous opioid systems (endogenous opioids and opioid receptors) in neuronal development was examined in 10- and 21-day-old rats by utilizing an opioid antagonist (naltrexone) paradigm. Throughout the first 3 weeks of life, Sprague-Dawley rats were given daily subcutaneous injections of either 50 mg/kg naltrexone, a dosage that invoked a complete (24 hours/day) receptor blockade, or 1 mg/kg naltrexone, a dosage which intermittently blocked (4-6 hours/day) opioid receptors and exacerbated opioid action; animals injected with sterile water served as controls. Pyramidal cells from the frontoparietal cortex (layer III) and hippocampal field CA1, and cerebellar Purkinje cells, were impregnated by using the Golgi-Kopsch method; total and mean dendrite segment length, branch frequency, and spine concentration were analyzed morphometrically. Perturbations of endogenous opioid systems caused region-dependent alterations in dendrite complexity and/or spine concentration in all brain areas. Continuous opioid receptor blockade resulted in dramatic increases in dendrite and/or spine elaboration compared to controls at 10 days in all brain regions; however, these increases were only evident in the hippocampus at 21 days. With intermittent blockade, dendrite and/or spine growth were often subnormal, being predominant at day 21. Our results indicate that endogenous opioid systems are critical regulators of neuronal differentiation, and they control growth through an inhibitory mechanism. Considering previous findings demonstrating that neurobehavioral ontogeny is dependent on endogenous opioid-opioid receptor interactions, the present results suggest an opioid-dependent, structure-function relationship between neuronal and behavioral maturation.
利用阿片类拮抗剂（纳曲酮）范式，研究了内源性阿片系统（内源性阿片和阿片受体）在10日龄和21日龄大鼠神经元发育中的作用。在出生后的前三周，给斯普拉格-道利大鼠每日皮下注射50mg/kg纳曲酮（该剂量可引起完全性（每天24小时）受体阻断）或1mg/kg纳曲酮（该剂量可间歇性阻断（每天4 - 6小时）阿片受体并增强阿片作用）；注射无菌水的动物作为对照。采用高尔基-科普施方法对额顶叶皮质（III层）、海马CA1区的锥体细胞以及小脑浦肯野细胞进行染色；对树突总长度和平均长度、分支频率以及棘突密度进行形态计量学分析。内源性阿片系统的扰动在所有脑区均引起了树突复杂性和/或棘突密度的区域依赖性改变。与对照组相比，持续的阿片受体阻断在10日龄时导致所有脑区的树突和/或棘突明显增多；然而，这些增加在21日龄时仅在海马中明显。间歇性阻断时，树突和/或棘突生长常常低于正常水平，在21日龄时更为明显。我们的结果表明，内源性阿片系统是神经元分化的关键调节因子，并且它们通过抑制机制控制生长。考虑到先前的研究结果表明神经行为个体发育依赖于内源性阿片 - 阿片受体相互作用，目前的结果提示了神经元与行为成熟之间存在阿片依赖的结构 - 功能关系。
