Repeated prenatal cocaine increases met-enkephalin immunoreactivity in respiratory-related medulla of developing...

Repeated prenatal exposure to cocaine is associated with attenuated respiratory and arousal responses in infants and piglets. As the normal development of these functions is influenced by medullary opioid systems, the present study explored the possible contribution of the opioid systems to the attenuation induced by cocaine. Methionine-enkephalin (met-enkephalin), an endogenous opioid peptide, was delineated by immunocytochemistry in respiratory- and arousal-related medullary regions of relatively immature (6-7-day-old) and more mature piglets (20-21-day-old). The animals were either unexposed, or exposed prenatally to 2 mg/kg cocaine four times daily administered to the pregnant sows intravenously throughout the last third of gestation. At control, met-enkephalin was found in the neurons, fibers and terminals of the respiratory- and arousal-related medullary regions throughout the age range studied. Prenatal cocaine exposure increased met-enkephalin immunoreactivity in the respiratory-related hypoglossal and solitary tract nuclei of both age groups. These findings support a modulatory role of met-enkephalin in the normal development of respiratory control, and an involvement of this peptide in the attenuation of respiration by repeated prenatal exposure to cocaine.