Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, New York, USA.
Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, The Rockefeller University, New York, New York, USA.
J Comp Neurol. 2021 Jul 1;529(10):2636-2657. doi: 10.1002/cne.25115. Epub 2021 Feb 8.
Chronic immobilization stress (CIS) results in sex-dependent changes in opioid peptide levels and receptor subcellular distributions within the rat dorsal hippocampus, which are paralleled with an inability for males to acquire conditioned place preference (CPP) to oxycodone. Here, RNAScope in situ hybridization was used to determine the expression of hippocampal opioid peptides and receptors in unstressed (US) and CIS estrus female and male adult (∼2.5 months old ) Sprague Dawley rats. In all groups, dentate granule cells expressed PENK and PDYN; additionally, numerous interneurons expressed PENK. OPRD1 and OPRM1 were primarily expressed in interneurons, and to a lesser extent, in pyramidal and granule cells. OPRK1-was expressed in sparsely distributed interneurons. There were few baseline sex differences: US females compared to US males had more PENK-expressing and fewer OPRD1-expressing granule cells and more OPRM1-expressing CA3b interneurons. Several expression differences emerged after CIS. Both CIS females and males compared to their US counterparts had elevated: (1) PENK-expressing dentate granule cells and interneurons in CA1 and CA2/3a; (2) OPRD1 probe number and cell expression in CA1, CA2/3a and CA3b and the dentate gyrus; and (3) OPRK1-expressing interneurons in the dentate hilus. Also, CIS males compared to US males had elevated: (1) PDYN expression in granule cells; (2) OPRD1 probe and interneuron expression in CA2/3a; (3) OPRM1 in granule cells; and (4) OPRK1 interneuron expression in CA2/3a. The sex-specific changes in hippocampal opioid gene expression may impact network properties and synaptic plasticity processes that may contribute to the attenuation of oxycodone CPP in CIS males.
慢性束缚应激（CIS）导致雄性大鼠背侧海马体内阿片肽水平和受体亚细胞分布出现性别依赖性变化，同时雄性大鼠也无法获得对羟考酮的条件性位置偏爱（CPP）。在此，我们使用 RNAScope 原位杂交技术来确定未受应激（US）和 CIS 发情雌性和雄性成年（约 2.5 个月大）Sprague Dawley 大鼠海马体内阿片肽和受体的表达。在所有组中，齿状回颗粒细胞均表达 PENK 和 PDYN；此外，许多中间神经元表达 PENK。OPRD1 和 OPRM1 主要表达于中间神经元，在一定程度上也表达于锥体细胞和颗粒细胞。OPRK1 表达于稀疏分布的中间神经元。存在一些基本的性别差异：与 US 雄性相比，US 雌性的颗粒细胞中 PENK 表达增多，而 OPRD1 表达减少，CA3b 中间神经元中 OPRM1 表达增多。CIS 后出现了几种表达差异。与 US 对应物相比，CIS 雌性和雄性大鼠均出现以下情况：（1）齿状回颗粒细胞和 CA1、CA2/3a 中的中间神经元中 PENK 表达增加；（2）CA1、CA2/3a 和 CA3b 及齿状回中的 OPRD1 探针数量和细胞表达增加；（3）齿状回门区的 OPRK1 表达中间神经元增加。此外，与 US 雄性相比，CIS 雄性大鼠还出现以下情况：（1）颗粒细胞中 PDYN 表达增加；（2）CA2/3a 中的 OPRD1 探针和中间神经元表达增加；（3）颗粒细胞中 OPRM1 表达增加；（4）CA2/3a 中的 OPRK1 表达中间神经元增加。这些海马体内阿片基因表达的性别特异性变化可能会影响网络特性和突触可塑性过程，从而导致 CIS 雄性大鼠对羟考酮 CPP 的衰减。
