Hammer R P, Ricalde A A, Seatriz J V
Department of Anatomy and Reproductive Biology, University of Hawaii School of Medicine, Honolulu 96822.
Neurotoxicology. 1989 Fall;10(3):475-83.
Perinatal morphine administration affects neuronal growth in the developing animal. Neuronal packing density was reduced by morphine treatment in both primary somatosensory cortex and preoptic area of the hypothalamus. However, glial packing density was increased, but only in hypothalamus, which could reflect greater severity of opiate-induced neurotoxicity in hypothalamus. Cortical pyramidal neurons show morphine-induced reduction of basilar dendritic growth limited to late-developing terminal branches. This effect is completely reversed by concurrent naltrexone administration. This selective effect could be caused by morphine acting at opiate receptors to inhibit extrinsic determinants of dendritic growth (e.g., afferent supply). The ontogeny of opiate receptors is also affected by perinatal morphine administration in a regionally-dependent manner. Mureceptors are downregulated by morphine in hypothalamus, but not in cortex. Differential maturity of receptors in these regions could be a factor in such differential drug effects. Therefore, different critical periods for opiate action in different regions of the developing brain could exist.
围产期给予吗啡会影响发育中动物的神经元生长。在初级体感皮层和下丘脑视前区，吗啡处理均降低了神经元堆积密度。然而，胶质细胞堆积密度增加，但仅在下丘脑中出现，这可能反映出阿片类药物诱导的下丘脑神经毒性更为严重。皮层锥体神经元表现出吗啡诱导的基底树突生长减少，且仅限于发育较晚的终末分支。同时给予纳曲酮可完全逆转这种效应。这种选择性效应可能是由于吗啡作用于阿片受体，抑制树突生长的外在决定因素（如传入神经供应）所致。阿片受体的个体发生也受到围产期给予吗啡的区域依赖性影响。在下丘脑中，μ受体被吗啡下调，但在皮层中则不然。这些区域受体的不同成熟度可能是造成这种不同药物效应的一个因素。因此，在发育中大脑的不同区域可能存在阿片类药物作用的不同关键期。
