Enriched environment and social isolation differentially modulate addiction-related behaviors in male offspring of morphine-addicted dams: The possible role of mu-opioid receptors and Delta FosB in the brain reward pathway

摘要

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 and protein expression in brain reward circuits of male pups. 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 (STD), 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 Delta FosB and mu-opioid receptor proteins in the striatum and the midbrain of male offspring, respectively. 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 Delta FosB and mu-opioid receptor proteins expression. However, rearing in the EE declined Delta FosB protein expression. 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.