Prenatal cocaine raises mu-opioid receptor density in piglet cardiorespiratory medulla.
Repeated prenatal exposure to cocaine attenuates arousal and cardiorespiratory functions in neonates. This study explored the possible role of brainstem mu- and delta-opioid systems in these effects. Medullary sections were obtained from 6 to 7 (young) and 20 to 21-day-old (older) piglets either unexposed or exposed prenatally to a 2-mg/kg intravenous cocaine hydrochloride dose, injected to the pregnant sow four times a day during the last third of gestation. Mu- and delta-opioid receptor binding was assessed by quantitative autoradiography using, respectively, 125I-DAMGO (Tyr-D-Ala-Gly-N-Me-Phe-Gly-ol) and 125I-DPDPE (Tyr-D-Pen-Gly-pCl-Phe-D-Pen). At control, delta-, but not mu-opioid, receptor density increased with postnatal age. In contrast, cocaine-induced mu-, but not delta-opioid, receptor density increased 1) in the dorsal motor vagal (dmnX) and facial (nF) nuclei, and, at borderline significance level, in the cardiorespiratory-related gigantocellular reticular nucleus (nRG) of the young, and 2) in the spinal trigeminal nucleus and tract (nSp5), and in the cardiorespiratory-related medial solitary tract (nTSm) and lateral reticular (nRL) nuclei of both age groups. These findings support a possible participation of the mu-opioid system in the attenuation of arousal and cardiorespiration after repeated prenatal exposure to cocaine.
Moss
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Department of Pediatrics, McGill University Health Centre, Montreal, Quebec, Canada. immanuela.moss@muhc.mcgill.ca
Laferrière
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D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001345:Autoradiography; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects; D003042:Cocaine / Q000008:administration & dosage / Q000633:toxicity*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000378:metabolism; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D017465:Receptors, Opioid, delta / Q000187:drug effects / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000187:drug effects* / Q000378:metabolism*; D012143:Respiratory Physiological Phenomena / Q000187:drug effects; D013552:Swine; D013556:Swine, Miniature
D008024:Ligands; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D003042:Cocaine