The expression of opioid genes in non-classical reward areas depends on early life conditions and ethanol intake

Abstract

The young brain is highly sensitive to environmental influences that can cause long-term changes in neuronal function, possibly through altered gene expression. The endogenous opioid system continues to mature after birth and because of its involvement in reward, an inadequate maturation of this system could lead to enhanced susceptibility for alcohol use disorder. Recent studies show that the classical reward areas nucleus accumbens and ventral tegmental area are less affected by early life stress whereas endogenous opioids in non-classical areas, e.g. dorsal striatum and amygdala, are highly responsive. The aim was to investigate the interaction between early life conditions and adult voluntary ethanol intake on opioid gene expression. Male Wistar rats were exposed to conventional rearing, 15, or 360min of daily maternal separation (MS) postnatal day 1-21, and randomly assigned to ethanol or water drinking postnatal week 10-16. Rats exposed to early life stress (MS360) had increased opioid receptor gene (Oprm1, Oprd1 and Oprk1) expression in the dorsal striatum. Ethanol drinking was associated with lower striatal Oprd1 and Oprk1 expression solely in rats exposed to early life stress. Furthermore, rats exposed to early life stress had high inherent Pomc expression in the amygdala but low expression after ethanol intake. Thus, adverse events early in life induced changes in opioid gene expression and also influenced the central molecular response to ethanol intake. These long-term consequences of early life stress can contribute to the enhanced risk for excessive ethanol intake and alcohol use disorder seen after exposure to childhood adversity.

Environment-dependent striatal gene expression in the BACHD rat model for Huntington disease

“…3a ). Genes such as Oprk1 , Nrxn1 , and Nfia 38 , 39 that are known to be responsive to early life stress showed trends of differential expression (Supplementary Fig. S4 ).…”

“…On a molecular level, typical markers such Bdnf and Il1b showed very low expression in striatal tissue and did not allow deriving statistically significant results. Other genes including Oprk1 , Nrxn1 , and Nfia 38 , 39 that are known to be responsive to stress showed trends of changed expression in WT rats after maternal separation. However, no significantly expressed genes were identified comparing TG MS /TG SE or WT MS /WT SE , possibly related to general timings in the developmental gene regulatory program as many essential genes for striatal function and relevant in the context of HD may not yet be fully expressed during the first two postnatal weeks 65 .…”

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

“…In the brain, the arcuate nucleus of the hypothalamus processes POMC to produce the potent opioid peptide β-endorphin, and α-, β-, and γ-melanocortins [Ragavan et al, 1983;Rubinstein et al, 1996;Cowley et al, 2001;Romanova et al, 2015]. Besides the arcuate nucleus, POMC mRNA molecule has also been detected in several other mouse and rat brain regions, including the NAc, amygdala, hippocampus and cerebral cortex, in much lower levels than those in the arcuate nucleus [Civelli et al, 1982;Zhou et al, 1996Zhou et al, , 2013aLeriche et al, 2007;Bodnar, 2014;Granholm et al, 2017]. Using the POMC-eGFP mice, we observe that POMC expression in POMC-eGFP neurons can be visualized by GFP immunohistochemistry, and that there is a modest amount of POMC-eGFP neurons present in both the shell and core sub-regions of NAc [Zhou et al, 2013a].…”

Behavioral Profiling in Early Adolescence and Early Adulthood of Male Wistar Rats After Short and Prolonged Maternal Separation

“…An overview of the experimental timeline can be seen in Figure 1A, and a detailed description of the methods can be found in Comasco et al (2015) regarding the MS procedure and in Meyerson et al (2006) and Roman and Colombo (2009) for the MCSF procedure. Previously published results from the animal cohort (developmental body weights, voluntary ethanol consumption, and later genetic and epigenetic results) can be found in Bendre et al (2015Bendre et al ( , 2018, Comasco et al (2015); Nylander et al (2016), Todkar et al (2016); Granholm et al (2017), and Vrettou et al (2017).…”