Preliminary Study On The Effect Of Morphine Exposure During Embryonic Period On The Addiction Related Brain Regions In Rats

The use of opioids during pregnancy has become a serious public health problem worldwide,and morphine exposure during pregnancy can affect fetal brain development.The acute morphine-dependent rat model mimics the human addiction process,so embryonic morphine-exposed rats can be used to mimic the use of opioids during pregnancy.In this study,we established a model of morphine exposure in embryonic rats of SD rats.Behavioral and cognitive changes,as well as related molecular expression in key brain regions of addiction including hippocampus,prefrontal cortex,nucleus accumbens,and ventral tegmental area were observed in progeny rats by using behavioral and molecular biology studies Findings in this experiment:(1)Ethology: The morphine exposed male progeny in the water maze experiment had a shorter residence time in the platform;(2)Molecular aspects: The expression of TH in the female progeny m PFC of the morphine exposure group was significantly lower than that of the control group;While the expression level of HDAC4 in the morphine female group was higher than that in the control group.That of the morphine male group was lower than the normal saline group.Compared with the male control group,lower HDAC4 and HDAC5 expression levels were observed in the female control group..The female morphine group showed higher HDAC4 expression level in the m PFC than the control group.;(3)Enriched environmental behavior: In the three-box experiment of model animals,the progeny of the female morphine-rich environment group and the stranger 2 cage were significantly higher than the stranger 1;the enriched environment group female progeny rats spent longer in the social stimulus than in the object stimulus.Conclusion and significance:(1)Embryonic morphine exposure affects the cognitive ability of male offspring;(2)Embryonic morphine exposure significantly affected the expression level of female TH in m PFC;gender affected the expression of HDAC4 in HIP and m PFC,and affected the regulation of morphine on HDAC4 in HIP;(3)Enriched environment improved the social ability of female offspring exposed to morphine during embryonic period.Epigenetic factors may regulate the offspring of morphine exposure during embryonic period,and the enriched environment may have a certain intervention effect on the social communication of female progeny.