Changes in opioid receptors, opioid peptides and morphine antinociception in mice subjected to early life stress.

Recent studies have shown that the endogenous opioid system is considerably affected by early life stress such as child abuse. Here, we investigated whether early life stress changes the endogenous opioid receptors and their peptides, and if such stress impacts morphine antinociception. We used mice affected by maternal separation and social isolation (MSSI) as an early life stress model. In the tail-flick test, 10-week-old MSSI mice showed a significant decrease in morphine antinociception compared to age-matched control mice. The number of c-Fos-positive cells increased in the periaqueductal gray (PAG), nucleus accumbens, and thalamus of control mice after the morphine injections, whereas hardly any positive cells were detected in the same areas of MSSI mice. The expression of μ- and κ-opioid receptor (MOR and KOR, respectively) messenger RNA (mRNA) was significantly decreased in the PAG of MSSI mice, whereas KOR expression was significantly increased in the amygdala of MSSI mice. The expression of δ-opioid receptor (DOR) mRNA was significantly reduced in the PAG and rostral ventromedial medulla of MSSI mice compared to control mice. Moreover, the lack of morphine antinociception was observed in 18-week-old MSSI mice. Our findings suggest that the supraspinal opioid system may be affected by early life stress exposure, and that this exposure may impact morphine antinociception.