The effect of rearing in standard, isolated and enriched environmnets on addiction-related behaviors and molecular parameters in the adult male offspring born from morphine-dependent dams

Abstract

Introduction: Prenatal opioids exposure negatively affects the neurobehavioral abilities of children born from dependence dams. Adolescent housing conditions can buffer the detrimental impacts of early life experiences or contradictory can worsen individual psychosocial functions. The present study investigated the effects of maternal morphine dependence and different rearing conditions on behaviors, the dopamine system activity and protein expression in brain reward circuits of male pups. Material and methods: Female Wistar rats a week before conception, during pregnancy and lactation were injected twice daily with escalating doses of morphine or saline. On a postnatal day 21, male pups were weaned and subjected to three different environments for two months: standard, isolated (ISO), or enriched environment (EE). The anxiety and drug-related reward were measured using elevated plus maze, open field test, and conditioned place preference. Western blotting was used to determine the protein level of ΔFosB and μ-opioid receptor proteins in the striatum and the midbrain of male offspring, respectively. Moreover, the ventral striatum dopamine’s content, mRNA expressions of dopamine receptor 2were evaluated. Results: Results showed that maternal morphine administration dramatically increased anxiety-like and morphine place preference behaviors in offspring. Also, ISO condition aggravated these behavioral outcomes. While, rearing in EE could attenuate anxiety and morphine conditioning in pups. At molecular levels, maternal morphine exposure and social isolation markedly increased both of ΔFosB and μ-opioid receptor proteins expression. However, rearing in the EE declined ΔFosB protein expression. Furthermore, maternal morphine injections and social isolation reduced DA levels and altered expressions D2Rwithin the ventral striatum of these male offspring. However, post-weaning EE partially buffered these changes. Conclusion: Together, these findings help to elucidate long lasting impacts of early life morphine exposure and rearing environment on the behavioral and molecular profile of addicted individuals.