Chen W J, Parnell S E, West J R
Department of Human Anatomy and Medical Neurobiology, College of Medicine, Texas A&M University Health Science Center, College Station 77843-1114, USA.
Alcohol Clin Exp Res. 1999 Jan;23(1):18-25.
Previous research from our laboratory has shown that [ethanol (EtOH)] exposure during the brain growth spurt is detrimental to olfactory bulb development. This study extends those findings by examining the effects of EtOH, nicotine (NIC), and the combination of these drugs (EtOH/NIC) on olfactory bulb mitral cell numbers, as well as on various major neurotransmitter levels in neonatal rats. An artificial rearing paradigm was used in the present studies. These artificially reared pups were given 4 g/kg/day of EtOH and/or 6 mg/kg/day of NIC on postnatal day (PD) 4 to PD 9, except in the case of the acute neurochemistry study, in which the pups received treatment on PD 9 only. An artificially reared gastrostomy control group (GC) and a suckle control group were included. The mean total numbers of mitral cells in the EtOH and NIC groups were significantly reduced from that of the GC, as well as the volume of the left main olfactory bulb. There was no difference among any of the groups in mitral cell density. As for neurochemistry data, there was no difference in neurotransmitter levels among any of the groups in the repeat exposure regimen. There were, however, changes after the acute exposure (exposure on PD 9 only). Both serotonin and GABA levels were significantly increased only after NIC exposure. However, norepinephrine levels were significantly decreased after acute exposure in all three drug treatment groups, compared with that of the control group. Except for the GC control group, dopamine levels were not detected consistently after acute exposure to EtOH, NIC, or EtOH/NIC. Collectively, these findings demonstrate that exposure to EtOH or NIC individually during the brain growth spurt results in developmental deficits in the olfactory bulb, suggesting that both EtOH and NIC are neuroteratogens. Furthermore, this study demonstrated the capability of NIC to antagonize (protect) EtOH-induced mitral cell loss in the developing olfactory bulb.
我们实验室之前的研究表明，在脑发育激增期暴露于[乙醇（EtOH）]对嗅球发育有害。本研究通过检测乙醇、尼古丁（NIC）以及这两种药物的组合（EtOH/NIC）对新生大鼠嗅球二尖瓣细胞数量以及各种主要神经递质水平的影响，扩展了这些研究结果。本研究采用了人工饲养模式。这些人工饲养的幼崽在出生后第4天至第9天给予4 g/kg/天的EtOH和/或6 mg/kg/天的NIC，但急性神经化学研究除外，在该研究中幼崽仅在出生后第9天接受治疗。实验纳入了人工饲养的胃造口对照组（GC）和哺乳对照组。EtOH组和NIC组的二尖瓣细胞总数以及左主嗅球体积均显著低于GC组。各实验组间二尖瓣细胞密度无差异。关于神经化学数据，在重复暴露方案中，各实验组间神经递质水平无差异。然而，在急性暴露（仅在出生后第9天暴露）后出现了变化。仅在暴露于NIC后，血清素和GABA水平显著升高。然而，与对照组相比，在所有三个药物治疗组中，急性暴露后去甲肾上腺素水平均显著降低。除GC对照组外，急性暴露于EtOH、NIC或EtOH/NIC后，多巴胺水平未持续检测到。总体而言，这些研究结果表明，在脑发育激增期单独暴露于EtOH或NIC会导致嗅球发育缺陷，这表明EtOH和NIC均为神经致畸剂。此外，本研究证明了NIC能够拮抗（保护）发育中的嗅球中EtOH诱导的二尖瓣细胞损失。
