A history of opioid exposure in females increases the risk of metabolic disorders in their future male offspring.

Worldwide consumption of opioids remains at historic levels. Preclinical studies report intergenerational effects on the endogenous opioid system of future progeny following preconception morphine exposure. Given the role of endogenous opioids in energy homeostasis, such effects could impact metabolism in the next generation. Thus, we examined diet-induced modifications in F1 male progeny of morphine-exposed female rats (MORF1). When fed a high fat-sugar diet (FSD) for 6 weeks, MORF1 males display features of emerging metabolic syndrome; they consume more food, gain more weight, and develop fasting-induced hyperglycemia and hyperinsulinemia. In the hypothalamus, proteins involved in energy homeostasis are modified and RNA sequencing revealed down-regulation of genes associated with neuronal plasticity, coupled with up-regulation of genes associated with immune, inflammatory, and metabolic processes that are specific to FSD-maintained MORF1 males. Thus, limited preconception morphine exposure in female rats increases the risk of metabolic syndrome/type 2 diabetes in the next generation.

Adolescent experience affects postnatal ultrasonic vocalizations and gene expression in future offspring.

The present study measured postnatal ultrasonic vocalization (USV) and gene expression to examine potential changes in communication and/or attachment in the offspring of mothers exposed to morphine during adolescence. Offspring of morphine-exposed (Mor-F1), saline-exposed (Sal-F1), or non-handled control (Con-F1) female Sprague-Dawley rats were tested for separation-induced distress calls and maternal potentiation of distress calls during early postnatal development. We also examined relative expression of dopamine D2 receptor and mu opioid receptor (oprm1) mRNA in the nucleus accumbens and hypothalamus in these offspring, as their activity has been implicated in the regulation of postnatal USV in response to maternal separation. The findings indicate that adolescent experiences of future mothers, including their 10 daily saline or morphine injections, can result in significant region-specific differences in gene expression. In addition, these experiences resulted in fewer numbers of separation-induced distress calls produced by offspring. In contrast, augmented maternal potentiation was only observed in Mor-F1 offspring. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:714-723, 2016.

Enhanced maternal aggression and associated changes in neuropeptide gene expression in multiparous rats.

Although it has often been speculated that prior reproductive experience improves subsequent maternal care, few studies have examined specific changes in behavior during a 1st versus 2nd lactation. During lactation, mothers display heightened aggression toward male intruders, purportedly to protect vulnerable young. In the current study, maternal aggression was examined in primiparous and age-matched multiparous females on postpartum days 5 (PPD5) and PPD15. Expression of oxytocin, oxytocin receptor, arginine vasopressin, arginine vasopressin V1a receptors, and corticotrophin-releasing hormone mRNA was measured following aggression testing at both time points using real-time quantitative PCR in brain regions previously implicated in the regulation of maternal aggression. Multiparity significantly enhanced maternal aggression on PPD5 but not on PPD15. In addition, this increased aggression was associated with region- and gene-specific changes in mRNA expression. These findings indicate that reproductive experience enhances maternal aggression, an effect that may be mediated by region-specific alterations in neuropeptidergic activity. The adaptations observed in multiparous females provide an innate model for the study of neuroplasticity in the regulation of aggression.