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 (K-d and B-max) were assessed with H-3-labeled [D-Ala(2),Mephe(4),Gly-ol(5)] enkephalin (DAMGE). DAMGE binding was attenuated by 64% in P1 membranes, whereas P7 preparations showed no changes. The same buprenorphine regimen resulted in diminished DAMGE B-max 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 [H-3]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.