Adolescent Opiate Exposure in the Female Rat Induces Subtle Alterations in Maternal Care and Transgenerational Effects on Play Behavior

Abstract

The non-medical use of prescription opiates, such as Vicodin® and MSContin®, has increased dramatically over the past decade. Of particular concern is the rising popularity of these drugs in adolescent female populations. Use during this critical developmental period could have significant long-term consequences for both the female user as well as potential effects on her future offspring. To address this issue, we have begun modeling adolescent opiate exposure in female rats and have observed significant transgenerational effects despite the fact that all drugs are withdrawn several weeks prior to pregnancy. The purpose of the current set of studies was to determine whether adolescent morphine exposure modifies postpartum care. In addition, we also examined juvenile play behavior in both male and female offspring. The choice of the social play paradigm was based on previous findings demonstrating effects of both postpartum care and opioid activity on play behavior. The findings revealed subtle modifications in the maternal behavior of adolescent morphine-exposed females, primarily related to the amount of time females’ spend nursing and in non-nursing contact with their young. In addition, male offspring of adolescent morphine-exposed mothers (MOR-F1) demonstrate decreased rough and tumble play behaviors, with no significant differences in general social behaviors (i.e., social grooming and social exploration). Moreover, there was a tendency toward increased rough and tumble play in MOR-F1 females, demonstrating the sex-specific nature of these effects. Given the importance of the postpartum environment on neurodevelopment, it is possible that modifications in maternal–offspring interactions, related to a history of adolescent opiate exposure, plays a role in the observed transgenerational effects. Overall, these studies indicate that the long-term consequences of adolescent opiate exposure can impact both the female and her future offspring.

Development of Anxiety-Like Behavior via Hippocampal IGF-2 Signaling in the Offspring of Parental Morphine Exposure: Effect of Enriched Environment

“…Previous studies showed sex-differential behavior in the offspring of adolescent morphine-exposed rats (Byrnes, 2005;Johnson et al, 2011). Female offspring developed anxiety-like behavior, whereas male offspring demonstrated significantly enhanced morphine sensitization (Byrnes, 2005;Johnson et al, 2011). By contrast, in our study, both male and female offspring demonstrated anxiety-like behavior in the EPM and OFT procedures.…”

“…In the present study, adult morphine exposure did not affect general parameters perhaps because the animals had reached full sexual maturity when the drug was administered. Previous studies showed sex-differential behavior in the offspring of adolescent morphine-exposed rats (Byrnes, 2005;Johnson et al, 2011). Female offspring developed anxiety-like behavior, whereas male offspring demonstrated significantly enhanced morphine sensitization (Byrnes, 2005;Johnson et al, 2011).…”

Transgenerational modification of hippocampus TNF-α and S100B levels in the offspring of rats chronically exposed to morphine during adolescence

“…However, no study has investigated TNF-α or other cytokine levels in offspring of parents that were exposed to morphine. Several studies have revealed that opioids and opioid receptor expression may be altered in the offspring of parents with a background of morphine consumption (36,40,50). In fact, some consequences of chronic opioid consumption could be transgenerationally transmitted from parents to offspring.…”

Behavioral effects of perinatal opioid exposure

“…In rodents, a premating morphine exposure regimen (prior to pregnancy) had no effect on maternal behavior (Yim et al, 2006;Johnson et al, 2011) but induced long-term effects in offspring. In line with this finding, the female offspring of dams exposed to morphine during puberty displayed increased anxiety-like behavior both in the elevated plus-maze (EPM) and in a novel environment, possibly due to altered prolactin regulation (Byrnes, 2005a).…”