Paternal morphine alters offspring circulating beta-endorphin and corticosterone responses to oxycodone and cocaine

Abstract

Background: The opioid epidemic is leading to increased opioid use in adolescent populations. A growing body of evidence suggests that taking opioids during adolescence can disrupt normal development and impact future offspring. This study investigates the impact of paternal morphine exposure during adolescence on the hypothalamic-pituitary-adrenal (HPA) axis and release of endorphins in the offspring.

Methods: Male rats were administered morphine once a day from postnatal day (PND)30-39 using an increasing dosing regimen (5-25 mg/kg/day increasing every other day). They were mated during adulthood to drug naïve females. Their offspring were assessed for circulating beta-endorphin (βE) and corticosterone levels on PND30 (a timepoint prior to puberty in both sexes) in response to an acute injection of saline, oxycodone (1 mg/kg, i.p.) or cocaine (10 mg/kg, i.p.). At PND60, naïve littermates were catheterized so that a within-subjects design could be implemented to measure βE and corticosterone in response to saline, oxycodone, or cocaine.

Results: In males, βE levels in the plasma were increased in Mor-F1 males compared to Sal-F1 males regardless of the acute injection. This elevation was observed at PND30 and PND60. There were no differences in female circulating βE. In terms of corticosterone, male Mor-F1 offspring had blunted corticosterone at PND30, but elevated corticosterone in response to oxycodone at PND60. The females also tended towards lower corticosterone prior to puberty but had significantly elevated levels of circulating corticosterone following an acute cocaine injection.

Conclusion: Paternal morphine exposure during adolescence induces sex- and drug-specific changes in secreted hormone responses in offspring. The alterations in βE and corticosterone levels suggest mechanisms through which adolescent opioid exposure can impact endocrine functions of future offspring. These findings contribute to the understanding of intergenerational transmission of substance use effects.

Keywords: Beta endorphin; Cocaine; Corticosterone; Development; Morphine; Opioid; Oxycodone; Transgenerational.