Preconception opioids interact with mouse strain to alter morphine withdrawal in the next generation.

Abstract

Transgenerational effects of preconception morphine exposure in female rats have been reported which suggest that epigenetic modifications triggered by female opioid exposure, even when that exposure ends several weeks prior to pregnancy, has significant ramifications for their future offspring. The current study compares two mouse strains with well-established genetic variation in their response to mu opioid receptor agonists, C57BL/6J (BL6) and 129S1/svlmJ (129) to determine whether genetic background modifies the impact of preconception opioid exposure. Adolescent females from both strains were injected daily with morphine for a total of 10 days using an increasing dosing regimen with controls receiving saline. Several weeks after their final injection, aged-matched BL6 and 129 morphine (Mor-F0) or saline (Sal-F0) females were mated with drug naïve males to generate Mor-F1 and Sal-F1 offspring, respectively. As adults, F1 mice were made morphine dependent using thrice daily morphine injections for 4 days. On day 5, mice were administered either saline or morphine followed 3 h later by naloxone. Behavioral and physiological signs of withdrawal were then measured. Regardless of strain or sex, morphine-dependent Mor-F1 mice had significantly lower levels of withdrawal-induced corticosterone but significantly higher glucose levels when compared to Sal-F1 controls. In contrast, both strain- and preconception opioid exposure effects on physical signs of morphine dependence were observed.