Inglefield J R, Bitran D, Olschowka J A, Kellogg C K
Department of Neurobiology, University of Rochester, NY 14627.
Brain Res Bull. 1993;31(3-4):353-9. doi: 10.1016/0361-9230(93)90227-3.
Earlier work demonstrated that prenatal exposure to diazepam (DZ) selectively affected the noradrenergic (NE) terminals in the hypothalamus, leading to decreased basal NE levels, turnover rate, and release in adult offspring as well as altered responses to stressors in these NE projections. The exposure also affected plasma hormonal responses to stressors. In the present work, we used immunocytochemistry to study the effects of prenatal DZ exposure on NE terminals and on corticotropin-releasing factor (CRF)-containing neurons in the paraventricular nucleus (PVN) of the hypothalamus. DZ exposure (2.5 or 10 mg/kg over gestational days 14-20) led to a decrease in dopamine-beta-hydroxylase (DBH)-immunoreactivity (-ir) and a decrease in CRF-ir containing cells within the PVN of adult rats. The exposure also decreased DBH-ir in the ventral portion of the bed nucleus of the stria terminalis (BNST) but did not affect CRF-ir in the oval nucleus of BNST. Therefore, this study provides anatomic evidence that targeting benzodiazepine binding sites prenatally affects two neurotransmitter systems involved in responses to stressors.
早期研究表明，产前接触地西泮（DZ）会选择性地影响下丘脑的去甲肾上腺素能（NE）终末，导致成年子代的基础NE水平、周转率和释放量降低，以及这些NE投射对应激源的反应改变。这种接触还会影响对应激源的血浆激素反应。在本研究中，我们使用免疫细胞化学方法来研究产前接触DZ对下丘脑室旁核（PVN）中NE终末和含促肾上腺皮质激素释放因子（CRF）的神经元的影响。接触DZ（在妊娠第14 - 20天给予2.5或10 mg/kg）导致成年大鼠PVN内多巴胺-β-羟化酶（DBH）免疫反应性（-ir）降低以及含CRF-ir的细胞减少。这种接触还使终纹床核（BNST）腹侧部分的DBH-ir降低，但不影响BNST椭圆核中的CRF-ir。因此，本研究提供了解剖学证据，即产前靶向苯二氮䓬结合位点会影响参与应激源反应的两个神经递质系统。
