<p>Prenatal opioid exposure is a growing clinical concern, yet the impact of maternal control over drug intake on long-term offspring outcomes remains unclear. Here, we utilized a translational rat model to examine how the mode of oxycodone administration during pregnancy influences substance use vulnerability in adult offspring. Female Sprague-Dawley rats (<i>n</i> = 10-11/group) were assigned to one of three groups: voluntary intravenous self-administration (Oxycodone-Lead), yoked non-contingent oxycodone delivery (Oxycodone-Yoked), or yoked saline control (Saline-Yoked). The dam self-administered oxycodone in 6h sessions for three weeks, 5 days/week, prior to conception and then daily throughout gestation. Offspring were cross-fostered to drug-naïve dams at birth. In adulthood, male and female offspring were evaluated for oxycodone (0.1 mg/kg/infusion) and cocaine (0.5 mg/kg/infusion) intravenous self-administration using fixed ratio (7 sessions FR1; 5 sessions FR5) and progressive ratio schedules (3 sessions), as well as drug-seeking under extinction conditions (1 session). Despite equivalent overall drug exposure, offspring of Oxycodone-Yoked dams exhibited enhanced motivated responding and drug-seeking behaviors. Female Oxycodone-Yoked offspring showed increased intake and motivated responding specifically for oxycodone, while Oxycodone-Yoked offspring of both sexes displayed augmented cocaine seeking and drug-seeking under extinction. Pearson’s correlations between maternal intake and offspring behavior were sex- and drug-specific and were only observed in the Oxycodone-Yoked group. These findings indicate that maternal control over drug intake, rather than opioid exposure per se, plays a critical role in shaping neurodevelopmental trajectories underlying substance use vulnerability. This study highlights the importance of considering patterns of maternal opioid use when assessing long-term developmental risks.</p>

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Maternal control during prenatal oxycodone exposure: differential effects of voluntary versus involuntary self-administration on offspring substance use vulnerability in rats

  • Chantal CA Aaron,
  • Kerri E. Budge,
  • Sara B. Isgate,
  • Fair M. Vassoler,
  • Elizabeth M. Byrnes

摘要

Prenatal opioid exposure is a growing clinical concern, yet the impact of maternal control over drug intake on long-term offspring outcomes remains unclear. Here, we utilized a translational rat model to examine how the mode of oxycodone administration during pregnancy influences substance use vulnerability in adult offspring. Female Sprague-Dawley rats (n = 10-11/group) were assigned to one of three groups: voluntary intravenous self-administration (Oxycodone-Lead), yoked non-contingent oxycodone delivery (Oxycodone-Yoked), or yoked saline control (Saline-Yoked). The dam self-administered oxycodone in 6h sessions for three weeks, 5 days/week, prior to conception and then daily throughout gestation. Offspring were cross-fostered to drug-naïve dams at birth. In adulthood, male and female offspring were evaluated for oxycodone (0.1 mg/kg/infusion) and cocaine (0.5 mg/kg/infusion) intravenous self-administration using fixed ratio (7 sessions FR1; 5 sessions FR5) and progressive ratio schedules (3 sessions), as well as drug-seeking under extinction conditions (1 session). Despite equivalent overall drug exposure, offspring of Oxycodone-Yoked dams exhibited enhanced motivated responding and drug-seeking behaviors. Female Oxycodone-Yoked offspring showed increased intake and motivated responding specifically for oxycodone, while Oxycodone-Yoked offspring of both sexes displayed augmented cocaine seeking and drug-seeking under extinction. Pearson’s correlations between maternal intake and offspring behavior were sex- and drug-specific and were only observed in the Oxycodone-Yoked group. These findings indicate that maternal control over drug intake, rather than opioid exposure per se, plays a critical role in shaping neurodevelopmental trajectories underlying substance use vulnerability. This study highlights the importance of considering patterns of maternal opioid use when assessing long-term developmental risks.