COCAINE EXPOSURE IN FETAL MONKEY CAUSES INCREASED DOPAMINE RECEPTOR BINDING

此前我们发现多巴胺D1、D2和D5受体的mRNA 胎儿吻侧前脑各亚型明显增多 暴露在可卡因中的恒河猴。本研究的目的是 是为了确定在怀孕期间接触可卡因是否也 增加胎儿大脑中的多巴胺受体结合密度。 给怀孕的猴子注射可卡因(3毫克/公斤；肌肉注射，n=3)或 生理盐水(n=3)，20-22天，每天4次 怀孕到第70天。定量受体放射自显影 第70天胎儿脑多巴胺D1样受体的研究 使用[~H]SCH23390的切片。[~3H]螺环酮用于表征 多巴胺D2样受体。受体放射自显影的图像分析 发现高密度多巴胺D1样受体结合在 纹状体、伏隔核(ACB)和黑质(SN)； 而在额叶皮质观察到较低的结合密度 缰核(Hb)。多巴胺D2样受体结合也是 在额叶皮质、纹状体和ACB中发现，但在 HB或SN。多巴胺受体的分布模式是 在对照和可卡因处理的动物中也是如此。然而，有一种 D1样受体的位点密度显著增加 纹状体(P&lt；0.05)和黑质(P&lt；0.01)的D2样受体。 可卡因处理动物与生理盐水处理动物的纹状体(P&lt；0.01) 控制。这些发现表明，D1样和D2样受体是 在多巴胺靶神经元中存在，而D2样自体受体可以 在第70天胎猴中脑未检出。目前的结果是， 加上我们之前的发现，进一步支持了 孕期接触可卡因导致合成减少的假说 和多巴胺的释放，导致多巴胺D1和D2受体 多巴胺靶区神经元表达上调。中国的骚乱 调节动机的多巴胺神经回路的发展， 奖励和运动控制将产生深远的功能后果。

Previously we found that dopamine D1, D2 and D5 receptor mRNA subtypes are significantly increased in the rostral forebrain of fetal rhesus monkeys exposed to cocaine. The purpose of the present study was to determine whether cocaine exposure during gestation also increases dopamine receptor binding densities in the fetal brain. Pregnant monkeys were treated with cocaine (3 mg/kg; i.m, n=3) or physiological saline (n=3), four times per day from days 20-22 of pregnancy until day 70. Quantitative receptor autoradiography of dopamine D1-like receptors was performed on day 70 fetal brain sections using [3H]SCH23390. [3H]Spiperone was used to characterize dopamine D2-like receptors. Image analysis of receptor autoradiograms revealed a high density dopamine D1-like receptor binding in the striatum, nucleus accumbens (ACB) and the substantia nigra (SN), whereas lower binding densities were observed in the frontal cortex and the habenula (Hb). Dopamine D2-like receptor binding was also found in the frontal cortex, striatum and ACB, but was not detected in the Hb or SN. The pattern of dopamine receptor distribution was the same in both control and cocaine-treated animals. However, there was a significant increase in the density of sites for D1-like receptors in the striatum (P<0.05) and SN (P<0.01) and for D2-like receptors in the striatum (P<0.01) of cocaine-treated animals versus saline-treated controls. These findings suggest that D1-and D2-like receptors are present in dopamine target neurons, whereas D2-like autoreceptors can not be detected in day 70 fetal monkey midbrain. The present results, together with our previous findings provide further support for the hypothesis that gestational cocaine exposure causes reduced synthesis and release of dopamine which leads to dopamine D1 and D2 receptor up-regulation in dopamine target neurons. Disturbances in the development of the dopamine neurocircuitry that mediate motivation, reward and motor control would have profound functional consequences.