Chronic stress differentially altersmRNAexpression of opioid peptides and receptors in the dorsal hippocampus of female and male rats

Abstract

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.

Acute Delta 9‐tetrahydrocannabinol administration differentially alters the hippocampal opioid system in adult female and male rats

“…(2010)]. The presence of DOR‐immunoreactivity (‐ir) with AB1560 in interneurons and pyramidal cells in the rat hippocampus is consistent with mRNA expression (Johnson et al., 2020; Mansour et al., 1994) and binding (Crain et al., 1986; Gulya et al., 1986; Mansour et al., 1987; McLean et al., 1987) for DOR in this species.…”

“…Furthermore, no detectable labeling of this antibody is seen in Western blots of COS-7 cells (see Supporting information Figure S1 in Williams et al 2011a), which do not endogenously express DORs (Kieffer et al, 1992) and in the dorsal raphe of DOR knockout mice [see Supporting information Figure S1 in Bie et al (2010)]. The presence of DOR-immunoreactivity (-ir) with AB1560 in interneurons and pyramidal cells in the rat hippocampus is consistent with mRNA expression (Johnson et al, 2020;Mansour et al, 1994) and binding (Crain et al, 1986;Gulya et al, 1986;Mansour et al, 1987;McLean et al, 1987) for DOR in this species.…”

“…These changes in CIS males also are accompanied by a downregulation in the expression of several plasticity genes and proteins (Randesi et al., 2018). Additionally, our recent studies have shown that CIS “resets” baseline sex differences in opioid gene expression in a manner that would promote opioid‐mediated learning in females, but not in males (Johnson et al., 2020). The sex‐specific changes in the hippocampal opioid system likely impact network properties and synaptic plasticity processes that contribute to the attenuation of oxycodone CPP in CIS males (Bellamy et al., 2019; Reich et al., 2019).…”

Effects of Cannabinoid Exposure during Neurodevelopment on Future Effects of Drugs of Abuse: A Preclinical Perspective

“…In certain instances, it appeared that Δ 9 -THC exposure significantly affected mRNA expression of opioid-related units during the prenatal period, with these alterations affecting the opioid system long into adulthood. This explanation received recent validation with other paradigms also demonstrating a proclivity of Δ 9 -THC to differentially alter the mRNA expression of opioid peptides and receptors [ 135 ]. Such molecular alterations may reflect the secondary means of dopaminergic activity regulation previously mentioned.…”

Cohort-based analysis of paternal opioid use in relation to offspring’s BMI and plasma lipid profile

“…Our sensitivity analysis in sons and daughters indicates that paternal regular use of opioid (inhaling) is associated with higher odds ratio of obesity only in sons (201% increase in final adjusted model), and no significant increase was observed in daughters. The underlying reason for this differential response of male and female offspring to parental opioid inhaling may be a cultural factor that sons are more in company of their fathers at the time of opioid inhaling, or it may be the biologically known sex differences in response to opioids based on the differences in neuroimmune and hormonal systems [29][30][31][32][33][34] . www.nature.com/scientificreports/ On the other hand, we found that paternal opioid use pre-fatherhood is significantly associated lower odds ratio of underweight in offspring.…”