Maternal deprivation increases vulnerability to morphine dependence and disturbs the enkephalinergic system in...

Maternal deprivation can trigger long-lasting molecular and cellular modifications in brain functions and might facilitate the appearance of pathogenic behaviors. This study focuses on the vulnerability to develop morphine dependence in adult rats that were separated from their mother and littermates for 3 h per day for 14 d after birth and examines the adaptive changes in the enkephalinergic pathways. Place-preference conditioning was observed with 2 mg/kg morphine in deprived rats, whereas 5 mg/kg morphine was necessary to induce conditioning in nondeprived animals. A prolonged morphine conditioning was shown in deprived rats. A strong increase in oral morphine self-administration behavior and preference was observed in deprived rats. Only a very slight increase in preference for sucrose solution, a more ethological reinforcer known to interact with the opioid system, was shown in deprived rats. These results indicate that this postnatal environment change leads to a hypersensitivity to the reinforcing properties of morphine and to the development of morphine dependence. A significant decrease in preproenkephalin mRNA expression was observed in the nucleus accumbens and the caudate-putamen nucleus of deprived rats. The basal extracellular levels of the Met-enkephalin-like immunoreactivity in the nucleus accumbens were significantly lower in deprived rats when compared with nondeprived animals, whereas no change in mu-opioid receptor binding occurred. These results strongly support that maternal deprivation leads to a basal hypoactivity of the enkephalinergic system and hypersensitivity to morphine effects. Together, our results suggest that maternal deprivation in pups likely represents a risk factor for morphine dependence in adult rats.