Chen Hao, Parker Steven L, Matta Shannon G, Sharp Burt M
Department of Pharmacology, University of Tennessee Health Science Center, Suite 115 Crowe Building, 874 Union Avenue, Memphis, TN 38163, USA.
Eur J Neurosci. 2005 Jul;22(2):380-8. doi: 10.1111/j.1460-9568.2005.04229.x.
Children of women who smoked during pregnancy are at increased risk of dependence when smoking is initiated during adolescence. We previously reported that gestational nicotine exposure attenuated dopamine release induced by nicotine delivered during adolescence. In this study, we determined the effects of gestational nicotine exposure on nicotinic cholinergic receptor (nAChR) expression. Timed pregnant rats received nicotine (2 mg/kg/day) or vehicle via mini-osmotic pumps during gestation. Treatments continued in pups via maternal nursing during postnatal days (PN) 2-14 (equivalent to the human in utero third trimester). On PN35, 125I-epibatidine binding to nAChR was measured. The Bmax values (fmol/mg) in prefrontal cortex (PFC), nucleus accumbens (NAcc), substantia nigra (SN) and ventral tegmental area (VTA) were reduced by 26.6% (P<0.05), 32.6% (P<0.01), 23.0% (P<0.01) and 27.6% (P<0.05), respectively. In addition, gender differences were found in vehicle-treated groups; in SN and VTA, females were 79.3% (P<0.005) and 82.9% (P=0.08) of males, respectively. The expression of nAChR subunit mRNAs was measured using real-time RT-PCR on laser-capture microdissected tissues. In adolescent VTA, gestational nicotine exposure reduced (P<0.05) nAChR subunit mRNAs encoding alpha3 (53.0%), alpha4 (23.9%), alpha5 (46.7%) and beta4 (61.4%). In NAcc core, the treatment increased alpha3 mRNA (75.8%). In addition, the number of neurons in VTA was reduced by 15.0% (P<0.001). These studies indicate that gestational exposure to nicotine induces long-lasting changes in nAChR expression that may underlie the vulnerability of adolescents to dependence on nicotine.
孕期吸烟女性的子女在青春期开始吸烟时，成瘾风险会增加。我们之前报道过，孕期尼古丁暴露会减弱青春期给予尼古丁所诱导的多巴胺释放。在本研究中，我们确定了孕期尼古丁暴露对烟碱型胆碱能受体（nAChR）表达的影响。定时怀孕的大鼠在孕期通过微型渗透泵接受尼古丁（2毫克/千克/天）或溶剂。在出生后第2 - 14天（相当于人类子宫内的第三个 trimester），通过母鼠哺乳继续对幼崽进行处理。在出生后第35天，测量125I - 埃博霉素与nAChR的结合情况。前额叶皮质（PFC）、伏隔核（NAcc）、黑质（SN）和腹侧被盖区（VTA）的Bmax值（飞摩尔/毫克）分别降低了26.6%（P<0.05）、32.6%（P<0.01）、23.0%（P<0.01）和27.6%（P<0.05）。此外，在接受溶剂处理的组中发现了性别差异；在SN和VTA中，雌性分别为雄性的79.3%（P<0.005）和82.9%（P = 0.08）。使用实时RT - PCR在激光捕获显微切割组织上测量nAChR亚基mRNA的表达。在青春期VTA中，孕期尼古丁暴露降低了（P<0.05）编码α3（53.0%）、α4（23.9%）、α5（46.7%）和β4（61.4%）的nAChR亚基mRNA。在NAcc核心区，该处理增加了α3 mRNA（75.8%）。此外，VTA中的神经元数量减少了15.0%（P<0.001）。这些研究表明，孕期尼古丁暴露会诱导nAChR表达的长期变化，这可能是青少年易对尼古丁成瘾的基础。
