Stanwood G D, Washington R A, Shumsky J S, Levitt P
Department of Neurobiology, University of Pittsburgh School of Medicine, E1440 Biomedical Science Tower, Pittsburgh, PA 15261, USA.
Neuroscience. 2001;106(1):5-14. doi: 10.1016/s0306-4522(01)00256-1.
Administration of cocaine to pregnant rabbits produces robust and long-lasting anatomical alterations in the dopamine-rich anterior cingulate cortex of offspring. These effects include increased length and decreased bundling of layer III and V pyramidal neuron dendrites, increases in parvalbumin expression in the dendrites of interneurons, and increases in detectable GABAergic neurons. We have now examined multiple cortical regions with varying degrees of catecholaminergic innervation to investigate regional variations in the ability of prenatal cocaine exposure to elicit these permanent changes. All regions containing a high density of tyrosine hydroxylase-immunoreactive fibers, indicative of prominent dopaminergic input, exhibited alterations in GABA and parvalbumin expression by interneurons and microtubule-associated protein-2 labeling of apical dendrites of pyramidal neurons. These regions included the medial prefrontal, entorhinal, and piriform cortices. In contrast, primary somatosensory, auditory and motor cortices exhibited little tyrosine hydroxylase staining and no measurable cocaine-induced changes in cortical structure. From these data we suggest that the presence of dopaminergic afferents contributes to the marked specificity of the altered development of excitatory pyramidal neurons and inhibitory interneurons induced by low dose i.v. administration of cocaine in utero.
给怀孕的兔子注射可卡因会使其后代富含多巴胺的前扣带回皮质产生强烈且持久的解剖学改变。这些影响包括第三层和第五层锥体神经元树突长度增加和束集减少、中间神经元树突中小清蛋白表达增加以及可检测到的γ-氨基丁酸能神经元增加。我们现在检查了具有不同程度儿茶酚胺能神经支配的多个皮质区域，以研究产前接触可卡因引发这些永久性变化的能力的区域差异。所有含有高密度酪氨酸羟化酶免疫反应性纤维（表明有突出的多巴胺能输入）的区域，中间神经元的γ-氨基丁酸和小清蛋白表达以及锥体神经元顶端树突的微管相关蛋白-2标记都出现了改变。这些区域包括内侧前额叶、内嗅和梨状皮质。相比之下，初级体感、听觉和运动皮质几乎没有酪氨酸羟化酶染色，也没有可测量的可卡因诱导的皮质结构变化。根据这些数据，我们认为多巴胺能传入神经的存在有助于低剂量静脉注射子宫内可卡因诱导的兴奋性锥体神经元和抑制性中间神经元发育改变的显著特异性。
