Age-related mu-, delta-and kappa-opioid ligands in respiratory-related brain regions of piglets: effect of prenatal cocaine

Neonates, as compared to older subjects, exhibit increased signs of relative respiratory suppression such as apnea, periodic breathing and only transient hyperventilatory response to hypoxia. Prenatal cocaine exposure exaggerates the respiratory pattern disturbances observed in infants. As endogenous opioids cause central suppression of breathing, we tested their possible involvement in these effects by assessing opioid content in respiratory-related brainstem regions of 2 to 5 (young) and 18 to 22 (older) day-old piglets, unexposed or preexposed to cocaine during 0.66 to 1.0 gestation. The selected ages represent distinct stages in the postnatal development of respiration. beta-Endorphin, methionine-enkephalin, dynorphin A and dynorphin B from the tractus solitarii, ambigualis, gigantoreticularis and parabrachialis medialis nuclei were separated by high performance liquid chromatography, then quantified by radioimmunoassays. Opioid content was higher in the brain regions of the young than of the older piglets, and increased after cocaine exposure in both age groups, but more in the young. These findings support the possible contribution of high opioid content to the relative suppression of respiratory function in early life, and to the exaggerated respiratory dysrhythmia observed in cocaine preexposed neonates.