Hypoxia after prenatal cocaine attenuates striatal dopamine and neurotrophic activity

Abstract

We have previously shown that newborn rabbits exposed to cocaine prenatally have an altered cardiorespiratory response to hypoxia. We report the effect of postnatal hypoxia on brain DA and neurotrophic activity in New Zealand White rabbit pups ( n = 41) born to cocaine-exposed does (30 mg/kg/day SC from days 7–15 of a 32-day gestation = COCaine) and control does (sterile H 2O = VEHicle). Four to 6-day-old pups were exposed to 20 min of room air (0.21 fractional inspired oxygen tension, F 1O 2). One third of each group was then exposed to 20 min of either 0.15 (moderate hypoxia) or 0.08 (severe hypoxia) F 1O 2. Immediately following hypoxic challenge the pups were sacrificed. Striatal tissue extracts were subsequently assessed for DA and striatal trophic activity by monitoring the number of neuron specific enolase immunoreactive (NSEir) cells in mesencephalic culture following incubation with striatal extracts. Increasing the severity of hypoxia increased DA content ( p < 0.005), but reduced DA activity ( p < 0.0001) and trophic activity ( p < 0.001). Cocaine exposure reduced striatal DA ( p < 0.005) as well as NSEir ( p < 0.001) in all conditions relative to vehicle-treated controls. These data suggest that prenatal cocaine exposure enhances the vulnerability of the DA system to the stress of hypoxia, possibly through alterations in neurotrophic activity.