Maternal deprivation effect on morphine-induced CPP is related to changes in opioid receptors in selected rat brain regions (hippocampus, prefrontal cortex, and nucleus accumbens)

Abstract

Early-life environmental conditions affect offspring's development. Maternal deprivation (MD) can induce persistent changes that give rise to neuropsychiatric diseases including substance abuse disorders. However, long-lasting mechanisms that determine vulnerability to drug addiction remain unknown. We hypothesized that MD could induce changes in Opioid system, HPA (hypothalamic-pituitary-adrenal) axis, and BDNF (brain-derived neurotrophic factor), so may be involved in the drug abuse in later life. Male offspring of Wistar rats (n = 8 per group) were subjected to 3 h of daily MD during postnatal days 1–14. In adulthood, morphine-induced CPP (conditioned place preference) was investigated using two doses of morphine (3 and 5 mg/kg). Serum corticosterone level was measured by ELISA method. The expression level of genes in selected brain regions (hippocampus, prefrontal cortex, and nucleus accumbens) was determined by qPCR (quantitative PCR). A greater morphine-induced CPP was observed in MD rats with 3 and 5 mg/kg morphine compared to controls. MD group had a higher corticosterone level. A significant decrease was observed in the expression of BDNF gene (in all of the selected brain regions) and GR (glucocorticoid receptor) gene (in the hippocampus and nucleus accumbens) in MD rats. Also, a significant increase in the expression of μ Opioid receptor (in all of the selected brain regions) and κ Opioid receptor (in the prefrontal cortex and nucleus accumbens) was observed in MD rats. Our results suggest that MD induces alterations in the HPA axis function, BDNF level, and Opioid receptors system that enhance vulnerability to morphine at adulthood.