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Rationale <p>Prenatal opioid exposure (POE) can disrupt the development of dopamine and opioid systems, potentially altering behavioral sensitization in adulthood.</p> Objectives <p>This study examined the effects of gestational oxycodone (OXY) self-administration on quinpirole-induced locomotor sensitization in adult offspring and on gene expression in the nucleus accumbens (NAc) core, a region specifically involved in the expression phase of behavioral sensitization.</p> Methods <p>Female rats self-administered OXY beginning three weeks prior to conception and continuing throughout pregnancy. All offspring were then reared by drug naïve foster dams. As adults, male and female offspring were assessed for locomotor sensitization following repeated administration of the dopamine D2/D3 receptor agonist quinpirole. Expression of dopamine- and opioid-related genes was measured in the nucleus accumbens (NAc) core.</p> Results <p>Repeated quinpirole elicited robust locomotor sensitization across all groups. POE did not significantly alter sensitization magnitude; however, sex differences were evident, with males showing reduced locomotor responses compared to females. Despite the absence of behavioral differences, in males, POE was associated with downregulation of <i>OPRM1</i>,<i> OPRD1</i>,<i> DRD1</i>,<i> DRD2</i>,<i> PENK</i>, and <i>PDYN</i> in the NAc core. No significant effects of POE on gene expression changes were observed in females.</p> Conclusions <p>POE does not impact quinpirole-induced locomotor sensitization but influences sex-specific molecular alterations in NAc core opioid and dopamine pathways, highlighting potential long-term effects of POE on other opioidergic and/or dopaminergic -mediated behaviors.</p>

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Prenatal oxycodone exposure produces sex-specific alterations in nucleus accumbens core gene expression without affecting quinpirole-induced locomotor sensitization in adult rats

  • 期刊论文

  • 发表日期：

    2026年4月10日

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  • Chantal C. A. Aaron,
  • Fair M. Vassoler,
  • Elizabeth M. Byrnes

摘要

Rationale

Prenatal opioid exposure (POE) can disrupt the development of dopamine and opioid systems, potentially altering behavioral sensitization in adulthood.

Objectives

This study examined the effects of gestational oxycodone (OXY) self-administration on quinpirole-induced locomotor sensitization in adult offspring and on gene expression in the nucleus accumbens (NAc) core, a region specifically involved in the expression phase of behavioral sensitization.

Methods

Female rats self-administered OXY beginning three weeks prior to conception and continuing throughout pregnancy. All offspring were then reared by drug naïve foster dams. As adults, male and female offspring were assessed for locomotor sensitization following repeated administration of the dopamine D2/D3 receptor agonist quinpirole. Expression of dopamine- and opioid-related genes was measured in the nucleus accumbens (NAc) core.

Results

Repeated quinpirole elicited robust locomotor sensitization across all groups. POE did not significantly alter sensitization magnitude; however, sex differences were evident, with males showing reduced locomotor responses compared to females. Despite the absence of behavioral differences, in males, POE was associated with downregulation of OPRM1, OPRD1, DRD1, DRD2, PENK, and PDYN in the NAc core. No significant effects of POE on gene expression changes were observed in females.

Conclusions

POE does not impact quinpirole-induced locomotor sensitization but influences sex-specific molecular alterations in NAc core opioid and dopamine pathways, highlighting potential long-term effects of POE on other opioidergic and/or dopaminergic -mediated behaviors.