Psychopharmacology · 2023
Effect of prenatal and early post-natal oxycodone exposure on the reinforcing and antinociceptive effects of oxycodone in adult C57BL/6 J mice.
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Zhang Yong, Butelman Eduardo R, Kreek Mary Jeanne
Аннотация
UNLABELLED: Abuse of opioids (mu-opioid agonists such as oxycodone) among parents during the gestation and early post-natal period is a concern for the long-term health of the offspring, beyond potential neonatal withdrawal symptoms. However, there is only limited information on such effects.
OBJECTIVES: We examined how prenatal, and early-post natal oxycodone exposure affected opioid addiction behaviors.
METHODS: Adult male and female C57BL/CJ mice housed separately were first injected with ascending doses of oxycodone 1 time/day (1 mg/kg × 10 days, 1.5 mg/kg × 10 days, 2 mg/kg × 10 days, s.c.) whereas control mice were injected with saline. Newly formed parental dyads were then housed together and continued to receive ascending doses of oxycodone (3 mg/kg × 10 days, 4 mg/kg × 10 days, 5 mg/kg × 10 days, 6 mg/kg × 10 days or saline, s.c.) or saline during mating and gestation until the birth of the litter. The dams continued to receive oxycodone or saline through lactation, until F1 offspring were weaned. Upon reaching adulthood (12 weeks of age), male and female F1 offspring were examined in intravenous self-administration (IVSA) of oxycodone, on oxycodone-induced conditioned place preference (CPP) and oxycodone-induced antinociception.
RESULTS: Adult F1 male and female offspring of parental dyads exposed to oxycodone self-administered more oxycodone, compared to offspring of control parental dyads. Ventral and dorsal striatal mRNA levels of genes such as Fkbp5 and Oprm1 were altered following oxycodone self-administration.
CONCLUSION: Prenatal and early post-natal oxycodone exposure enhanced oxycodone self-administration during adulthood in the C57BL/6 J mice.
OBJECTIVES: We examined how prenatal, and early-post natal oxycodone exposure affected opioid addiction behaviors.
METHODS: Adult male and female C57BL/CJ mice housed separately were first injected with ascending doses of oxycodone 1 time/day (1 mg/kg × 10 days, 1.5 mg/kg × 10 days, 2 mg/kg × 10 days, s.c.) whereas control mice were injected with saline. Newly formed parental dyads were then housed together and continued to receive ascending doses of oxycodone (3 mg/kg × 10 days, 4 mg/kg × 10 days, 5 mg/kg × 10 days, 6 mg/kg × 10 days or saline, s.c.) or saline during mating and gestation until the birth of the litter. The dams continued to receive oxycodone or saline through lactation, until F1 offspring were weaned. Upon reaching adulthood (12 weeks of age), male and female F1 offspring were examined in intravenous self-administration (IVSA) of oxycodone, on oxycodone-induced conditioned place preference (CPP) and oxycodone-induced antinociception.
RESULTS: Adult F1 male and female offspring of parental dyads exposed to oxycodone self-administered more oxycodone, compared to offspring of control parental dyads. Ventral and dorsal striatal mRNA levels of genes such as Fkbp5 and Oprm1 were altered following oxycodone self-administration.
CONCLUSION: Prenatal and early post-natal oxycodone exposure enhanced oxycodone self-administration during adulthood in the C57BL/6 J mice.