Wang X H, Levitt P, Grayson D R, Murphy E H
Department of Anatomy and Neurobiology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Brain Res. 1995 Aug 14;689(1):32-46. doi: 10.1016/0006-8993(95)00528-x.
The effects of prenatal cocaine exposure on the development of the rabbit cerebral cortex were studied. Two cortical areas were compared: primary visual cortex (VC) and anterior cingulate cortex (ACC). ACC was selected because behavioral deficits observed in cocaine-exposed infants suggest the involvement of ACC. In addition, ACC receives dense dopaminergic innervation and cocaine's action in inhibiting the re-uptake of dopamine is believed to underly the rewarding properties of cocaine. VC was selected as a control area because there is no evidence of behavioral deficits associated with visual perception in cocaine-exposed infants, and because VC receives minimal dopaminergic innervation. Two aspects of cortical development were studied: (i) cortical morphology, growth and cytoarchitectonic organization; and (ii) the development of the GABAergic neurotransmitter system. Measures of postnatal cortical growth, including cortical lamination, cell number and soma size, were compared in cocaine-exposed or control (saline) rabbits aged P5-P60. There was no difference between cocaine and saline animals in any of these parameters, and cortical cytoarchitecture appeared normal. However, despite the absence of major abnormalities in cortical development, we found that the number of GABA-immunoreactive neurons in cocaine-exposed animals was significantly higher than normal in ACC. This effect was highly consistent, was present in all laminae and at all ages studied, and persisted into maturity (P60). In contrast, in VC, the number of GABA-immunoreactive neurons in cocaine-exposed animals did not differ from normal. We suggest that increased GABA immunoreactivity may reflect a compensatory response to excessive excitatory input to ACC. A change in the balance of excitation and inhibition in ACC, reflecting 'noisy' or dysfunctional intracortical circuitry, may underly the emotional lability and attentional deficits characteristically described in infants exposed in utero to cocaine.
研究了产前接触可卡因对家兔大脑皮质发育的影响。比较了两个皮质区域：初级视觉皮质（VC）和前扣带回皮质（ACC）。选择ACC是因为在接触可卡因的婴儿中观察到的行为缺陷表明ACC参与其中。此外，ACC接受密集的多巴胺能神经支配，并且可卡因抑制多巴胺再摄取的作用被认为是可卡因具有奖赏特性的基础。选择VC作为对照区域是因为没有证据表明接触可卡因的婴儿存在与视觉感知相关的行为缺陷，并且VC接受的多巴胺能神经支配极少。研究了皮质发育的两个方面：（i）皮质形态、生长和细胞结构组织；（ii）GABA能神经递质系统的发育。比较了出生后P5 - P60的接触可卡因或对照（生理盐水）家兔的皮质生长指标，包括皮质分层、细胞数量和胞体大小。在这些参数中，可卡因组和生理盐水组动物之间没有差异，并且皮质细胞结构看起来正常。然而，尽管皮质发育没有重大异常，但我们发现接触可卡因动物的ACC中GABA免疫反应性神经元的数量显著高于正常水平。这种效应高度一致，在所研究的所有层和所有年龄段都存在，并持续到成熟阶段（P60）。相比之下，在VC中，接触可卡因动物的GABA免疫反应性神经元数量与正常水平没有差异。我们认为GABA免疫反应性增加可能反映了对ACC过度兴奋性输入的一种代偿反应。ACC中兴奋与抑制平衡的改变，反映了“嘈杂的”或功能失调的皮质内神经回路，可能是子宫内接触可卡因的婴儿所特有的情绪不稳定和注意力缺陷的基础。
