Transient down-regulation of neonatal rat brain mu-opioid receptors upon in utero exposure to buprenorphine.
Gestational actions of the mixed agonist-antagonist buprenorphine on mu- and kappa 1-opioid binding in neonatal and maternal rat brain were investigated. Upon exposure of pregnant rats to 0.5 mg/kg buprenorphine for 7 days prior to birth, postnatal day-one (P1) and P7 offspring brain mu-binding parameters (Kd and Bmax) were assessed with 3H-labeled [D-Ala2,Mephe4,Gly-ol5] enkephalin (DAMAGE). DAMAGE binding was attenuated by 64% in P1 membranes, whereas P7 preparations showed no changes. The same buprenorphine regimen resulted in diminished DAMGE Bmax values in mothers' brains, 2 but not 7 days after cessation of drug administration. Receptor density changes were not accompanied by alteration of mu-binding affinities. Although the postnatal developmental profile of kappa 1 opioid receptors in rat brain measured with [3H]U69593 revealed the presence of an ample number of sites for detection, their binding parameters in P1, P7 pups and mothers were unaffected by 0.5 mg/kg buprenorphine. In summary, buprenorphine administration to pregnant rats transiently down-regulates mu opioid receptors in neonatal and maternal brain.
E.A. Doisy Department of Biochemistry and Molecular Biology, St. Louis University School of Medicine, MO 63104-1079.
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Belcheva
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Dawn
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Barg
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McHale
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Ignatova
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Coscia
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D044482:Benzeneacetamides; D001923:Brain Chemistry / Q000502:physiology*; D002047:Buprenorphine / Q000494:pharmacology*; D015536:Down-Regulation / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000378:metabolism*
D000700:Analgesics; D044482:Benzeneacetamides; D004745:Enkephalins; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002047:Buprenorphine; C045444:U 69593