Maternal Deprivation Increases Vulnerability to Morphine Dependence and Disturbs the Enkephalinergic System in Adulthood

Abstract

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 -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.

Interactions between Early Life Stress, Nucleus Accumbens MeCP2 Expression, and Methamphetamine Self-Administration in Male Rats

“…The present study replicated our previous findings of ELS-induced increases in METH SA (Lewis et al, 2013;Lewis et al, 2015), which is also consistent with other drugs of abuse (Vazquez et al, 2005;Moffett et al, 2007). We also present novel findings that ELS alone increases MeCP2 expression in the NAc core, but not the NAc shell or the dorsal striatum.…”

Enhanced sensitivity to naltrexone-induced drinking suppression of fluid intake and sucrose consumption in maternally separated rats

“…In the nucleus accumbens, maternal separation results in a decrease in pre-proenkephalin mRNA and lower basal levels of Met-enkephalin-like immunoreactivity (Ploj & Nylander, 2003;Vazquez et al, 2005b). These findings along with our own raise the possibility that maternal separation alters the functionality and/or distribution of multiple opioid systems in the brain, any or all of which could result in the observed changes in reward.…”

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

“…Locomotor sensitization to repeated morphine is enhanced by maternal separation in rats (Kalinichev et al, 2002). Maternal separation also increases morphine CPP (Vazquez et al, 2005b(Vazquez et al, , 2007Michaels and Holtzman, 2008). Morphine CPP is enhanced in a model comparing artificial rearing to mother rearing in male rats (Lomanowska et al, 2006), and neonatally isolated rats consume more morphine than controls when given access via a two-bottle choice between morphine and water (Vazquez et al, 2005b).…”