(73) Pre-gestational oxycodone exposure impacts maternal motivation but not maternal caregiving or drug seeking in the postpartum mouse

Females are uniquely sensitive to drugs of abuse at specific points in their reproductive cycle, yet little is known about how opioid drugs affect the maternal (postpartum) female. Females’ endogenous opioid system mediates... [ view full abstract ]

Females are uniquely sensitive to drugs of abuse at specific points in their reproductive cycle, yet little is known about how opioid drugs affect the maternal (postpartum) female. Females’ endogenous opioid system mediates a number of maternally relevant physiological functions and reward processes. While gestational opioid exposure has been shown to impact offspring development, less is known about how opiate drugs impact the postpartum females’ maternal behavior and motivation for her offspring (pups), or how a history of opiate exposure, prior to pregnancy, might affect these behaviors. The present study assessed (a) the extent to which chronic exposure to oxycodone during adolescence, prior to pregnancy, altered a female’s subsequent response to her pups, and whether the unique hormonal and motivational state of the postpartum period act to reduce females’ preference for oxycodone. Adolescent female and male mice were exposed chronically to oxycodone or saline before entering spontaneous withdrawal. Females were bred and experienced a drug-free pregnancy. Following parturition, females’ maternal behavior and motivation and their conditioned preference for oxycodone was assessed. No major sex differences emerged in mice’s behavioral responses to oxycodone or degree of sensitization, or in the trajectory or severity of withdrawal. During the postpartum period, females’ maternal behaviors did not differ as a result of adolescent oxycodone exposure, suggesting that relatively stimulus-bound maternal responses remain intact. However, oxycodone-exposed females showed fewer approach behaviors in the maternal motivation test, suggesting that the oxycodone history may have impacted the incentive value attributed to pups. Individual differences in the strength of oxycodone place preference did not correspond to differences in maternal motivation or locomotor responses to oxycodone, but do suggest underlying neurobiological differences. The results suggest that opiate exposure in adolescence mediates the reorganizing of neural substrates involved in reward processing and saliency, such as the MPOA, the VTA, the nucleus accumbens, and the mesolimbic dopamine system and can cause shifts that may change mu-receptor density and create long-term changes in appetitive behaviors.