Opioid receptor-mediated changes in the NMDA receptor in developing rat and chicken

The use of opioids during pregnancy has been associated with neurodevelopmental toxicity in exposed children, leading to cognitive and behavioural deficits later in life. The N-methyl-D-aspartate receptor (NMDAR) subunit GluN2B plays critical roles in cerebellar development, and methadone has been shown to possess NMDAR antagonist effect. Consequently, we wanted to explore if prenatal opioid exposure affected GluN2B subunit expression and NMDAR function in rat and chicken cerebellum. Pregnant rats were exposed to methadone (10 mg/kg/day) or buprenorphine (1 mg/kg/day) for the whole period of gestation, using an osmotic minipump. To further examine potential effects of prenatal opioid exposure in a limited time window, chicken embryos were exposed to a 20 mg/kg dose of methadone or morphine on embryonic days 13 and 14. Western blot analysis of cerebella isolated from 14 days old rat pups exposed to buprenorphine showed significantly lower level of the GluN2B subunit, while the opioid exposed chicken embryo cerebellar GluN2B expression remained unaffected at embryonic day 17. However, we observed increased NMDA/glycine-induced calcium influx in cerebellar granule neurone cultures from opioid exposed chicken embryos. We conclude that prenatal opioid exposure leads to opioid receptor-dependent reduction in the postnatal expression of GluN2B in rat cerebella, and increase in NMDA-induced calcium influx in chicken embryo cerebella.