Cocaine treatment alters oxytocin receptor binding but not mRNA production in postpartum rat dams

Cocaine treatment alters oxytocin receptor binding but not mRNA production in postpartum rat dams
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DOI:
10.1016/j.npep.2006.03.002
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发表时间:
2006-06-01
期刊:
影响因子:
2.9
通讯作者:
Johns, J. M.
Johns, J. M.
中科院分区:
医学3区
文献类型:
--
作者:
Jarrett, T. M.;McMurray, M. S.;Johns, J. M.

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在大鼠母鼠中给予吉西他滨可卡因治疗导致催产素(OT)水平降低,整个杏仁核中催产素受体(OTR)结合密度上调和受体亲和力降低,所有这些都伴随着产后第六天母体攻击性的显著增加。没有妊娠药物治疗的大鼠母鼠接受了OT拮抗剂直接注入中央杏仁核(CeA)表现出类似的高水平的母亲对入侵者的侵略。此外,研究表明,下丘脑室旁核(PVN)的OT释放减少与大鼠母体攻击性增加一致。因此,可卡因诱导的OT系统动力学(水平,受体,生产和/或释放)的改变可能介导可卡因治疗后母体攻击性的增强,但可卡因影响OT系统的确切机制尚未确定。基于先前的研究,我们假设可卡因的作用的两种可能的机制将是,在CeA中特异性地增加OTR结合,以及在PVN中减少OT mRNA的产生。放射自显影和原位杂交分析进行产后第六天,妊娠治疗后,每天两次可卡因(15毫克/公斤)或生理盐水(1毫升/公斤)的大鼠母鼠的脑区域的靶向核。我们现在报告可卡因诱导的OTR结合密度的腹内侧下丘脑(VMH)和床核的终纹(BNST),但不是CeA的减少。可卡因处理后,室旁核中OT mRNA的产生没有显著变化。(c)2006爱思唯尔有限公司保留所有权利。
Gestational cocaine treatment in rat dams results in decreased oxytocin (OT) levels, up-regulated oxytocin receptor (OTR) binding density and decreased receptor affinity in the whole amygdala, all concomitant with a significant increase in maternal aggression on postpartum day six. Rat dams with no gestational drug treatment that received an infusion of an OT antagonist directly into the central nucleus of the amygdala (CeA) exhibited similarly high levels of maternal aggression towards intruders. Additionally, studies indicate that decreased OT release from the hypothalamic division of the paraventricular nucleus (PVN) is coincident with heightened maternal aggression in rats. Thus, it appears that cocaine-induced alterations in OT system dynamics (levels, receptors, production, and/or release) may mediate heightened maternal aggression following cocaine treatment, but the exact mechanisms through which cocaine impacts the OT system have not yet been determined. Based on previous studies, we hypothesized that two likely mechanisms of cocaine's action would be, increased OTR binding specifically in the CeA, and decreased OT mRNA production in the PVN. Autoradiography and in situ hybridization assays were performed on targeted nuclei in brain regions of rat dams on postpartum day six, following gestational treatment twice daily with cocaine (15 mg/kg) or normal saline (1 ml/kg). We now report cocaine-induced reductions in OTR binding density in the ventromedial hypothalamus (VMH) and bed nucleus of the stria terminalis (BNST), but not the CeA. There was no significant change in OT mRNA production in the PVN following cocaine treatment. (c) 2006 Elsevier Ltd. All rights reserved.