Pinheiro C R, Oliveira E, Manhães A C, Fraga M C, Claudio-Neto S, Younes-Rapozo V, Lotufo B M, Moura E G, Lisboa P C
Laboratory of Endocrine Physiology, Biology Institute, State University of Rio de Janeiro, Brazil.
Laboratory of Neurophysiology, Biology Institute, State University of Rio de Janeiro, Brazil.
Pharmacol Biochem Behav. 2015 Sep;136:87-101. doi: 10.1016/j.pbb.2015.07.012. Epub 2015 Jul 26.
Nicotine exposure causes the release of dopamine from the ventral tegmental area (VTA) to the nucleus accumbens (NAc). We have previously shown that maternal exposure to nicotine during lactation causes hyperleptinemia in dams and pups, and leptin is known to decrease dopamine release from the VTA. Here we evaluated whether maternal exposure to nicotine during lactation causes changes in dopamine and leptin signaling pathways at the end of exposure and after 5days of withdrawal in the: VTA, NAc, arcuate nucleus (ARC) and dorsal striatum (DS). On postnatal day (PN) 2, lactating Wistar rats were implanted with minipumps releasing nicotine (NIC; 6mg/kg/day, s.c.) or saline (C) for 14days. Offspring were tested in the elevated plus maze (EPM) and open field on PN14 or PN20, and euthanized on PN15 or PN21. Entries into the open arms and head dips in the EPM were reduced in NIC pups at P20. At weaning (PN21), NIC dams had: lower tyrosine hydroxylase (TH), higher OBRb and SOCS3 contents in VTA; lower TH, higher D1R, D2R and DAT contents in NAc; higher TH content in DS; and higher D2R and SOCS3 contents in ARC. On PN15, NIC offspring had higher D1R, D2R and lower DAT contents in NAc, while on PN21, they had lower DAT in DS, and lower pSTAT3 content in ARC. We evidenced that postnatal nicotine exposure induces relevant changes in the brain reward system of dams and pups, possibly associated with changes in leptinemia and increased offspring anxiety-like behavior.
尼古丁暴露会导致多巴胺从腹侧被盖区（VTA）释放到伏隔核（NAc）。我们之前已经表明，哺乳期母体暴露于尼古丁会导致母鼠和幼崽出现高瘦素血症，并且已知瘦素会减少VTA中多巴胺的释放。在此，我们评估了哺乳期母体暴露于尼古丁是否会在暴露结束时以及撤药5天后，在VTA、NAc、弓状核（ARC）和背侧纹状体（DS）中引起多巴胺和瘦素信号通路的变化。在出生后第2天（PN2），给哺乳期的Wistar大鼠植入释放尼古丁（NIC；6mg/kg/天，皮下注射）或生理盐水（C）的微型泵，持续14天。在PN14或PN20对后代进行高架十字迷宫（EPM）和旷场试验，并在PN15或PN21实施安乐死。在P20时，NIC幼崽进入EPM开放臂的次数和头部下垂次数减少。在断奶时（PN21），NIC母鼠的VTA中酪氨酸羟化酶（TH）含量较低，OBRb和SOCS3含量较高；NAc中TH含量较低，D1R、D2R和多巴胺转运体（DAT）含量较高；DS中TH含量较高；ARC中D2R和SOCS3含量较高。在PN15时，NIC后代的NAc中D1R、D2R含量较高，DAT含量较低，而在PN21时，它们的DS中DAT含量较低，ARC中磷酸化信号转导子和转录激活子3（pSTAT3）含量较低。我们证明，出生后尼古丁暴露会在母鼠和幼崽的脑奖赏系统中引起相关变化，这可能与瘦素血症的变化以及后代焦虑样行为增加有关。
